Geriatric Psychiatry

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Clinical Manual of
Geriatric Psychiatry
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Clinical Manual of
Geriatric Psychiatry
James E. Spar, M.D.
Professor of Clinical Psychiatry
Department of Psychiatry & Biobehavioral Sciences
Geffen School of Medicine at UCLA
Los Angeles, California
Asenath La Rue, Ph.D.

Senior Scientist
Wisconsin Alzheimer’s Institute
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin
Washington, DC
London, England
Note: The authors have worked to ensure that all information in this book is accurate
at the time of publication and consistent with general psychiatric and medical standards,
and that information concerning drug dosages, schedules, and routes of administration
is accurate at the time of publication and consistent with standards set by the U.S.
Food and Drug Administration and the general medical community. As medical
research and practice continue to advance, however, therapeutic standards may change.
Moreover, specific situations may require a specific therapeutic response not included
in this book. For these reasons and because human and mechanical errors sometimes
occur, we recommend that readers follow the advice of physicians directly involved in
their care or the care of a member of their family.
Books published by American Psychiatric Publishing, Inc., represent the views and
opinions of the individual authors and do not necessarily represent the policies and
opinions of APPI or the American Psychiatric Association.
Copyright © 2006 American Psychiatric Publishing, Inc.
ALL RIGHTS RESERVED
Manufactured in the United States of America on acid-free paper
10 09 08 07 06 5 4 3 2 1
First Edition
Typeset in Adobe’s Formata and AGaramond.
American Psychiatric Publishing, Inc.
1000 Wilson Boulevard
Arlington, VA 22209-3901
www.appi.org
Library of Congress Cataloging-in-Publication Data
Spar, James E.
Clinical manual of geriatric psychiatry / James E. Spar, Asenath La Rue.—1st ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58562-195-1 (pbk. : alk. paper)
1. Geriatric psychiatry—Handbooks, manuals, etc. 2. Older people—Mental
health—Handbooks, manuals, etc. 3. Older people—Psychology—Handbooks,
manuals, etc.
[DNLM: 1. Aged. 2. Mental Disorders—diagnosis. 3. Mental Disorders—therapy.
4. Age Factors. 5. Aging—psychology. WT 150 S736c 2006] I. La Rue, Asenath,
1948– II. Title.
RC451.4.A5S63 2006
618.97'689—dc22
2006005228
British Library Cataloguing in Publication Data
A CIP record is available from the British Library.
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
An Aging World . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Health and Functioning of Older Adults . . . . . . . . . . . . . . 3
Mental Disorders in Later Life . . . . . . . . . . . . . . . . . . . . . . 6
Barriers to Geriatric Mental Health Care. . . . . . . . . . . . . . 8
Diversity in Patterns of Health and Aging. . . . . . . . . . . .12
Working Effectively With Older Adults. . . . . . . . . . . . . . .15
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
2 Normal Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Conceptual Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21
Cognitive Abilities in Later Life: A Processing
Resource Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23
Personality and Emotional Changes . . . . . . . . . . . . . . . .38
Social Context of Aging . . . . . . . . . . . . . . . . . . . . . . . . . .43
Biological Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .48
Aging and the Clinical Process. . . . . . . . . . . . . . . . . . . . .50
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61
3 Mood Disorders—Diagnosis . . . . . . . . . . . . . . . . 67
“Normal” Grief (Bereavement) . . . . . . . . . . . . . . . . . . . .68
Complicated Grief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70
Depression Due to a General Medical Condition . . . . .70
Substance-Induced Mood Disorder . . . . . . . . . . . . . . . .76
Major Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80
Dysthymic Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91
Minor Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
Depressive Personality Disorder . . . . . . . . . . . . . . . . . . .95
Laboratory Evaluation of Depression . . . . . . . . . . . . . . .95
Psychological Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96
Symptom Rating Scales and Depression Screening . . .97
Assessing Suicidality in the Elderly . . . . . . . . . . . . . . . .105
Theories of Depression . . . . . . . . . . . . . . . . . . . . . . . . .107
Hypomania and Mania . . . . . . . . . . . . . . . . . . . . . . . . . .110
Mixed Mood Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . .117
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117
4 Mood Disorders—Treatment . . . . . . . . . . . . . . . 127

Psychotherapy for Geriatric Depression . . . . . . . . . . . .127
New Directions in Psychotherapy Research . . . . . . . . .130
Combined Psychotherapy and Pharmacotherapy . . . .132
Psychopharmacotherapy for Geriatric Depression . . .132
Psychopharmacotherapy for Psychotic Depression. . .156
Psychopharmacotherapy for Bipolar Depression. . . . .157
Electroconvulsive Therapy . . . . . . . . . . . . . . . . . . . . . . .157
Experimental Therapies . . . . . . . . . . . . . . . . . . . . . . . . .159
Complementary and Alternative Approaches . . . . . . .161
Hypomania and Mania . . . . . . . . . . . . . . . . . . . . . . . . . .162
Bipolar Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
5 Dementia and
Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . 173
Identifying the Dementia Syndrome. . . . . . . . . . . . . . .173
Common Etiologies of Dementia . . . . . . . . . . . . . . . . .186
Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . .192
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .221
Resources for Dementia Caregivers . . . . . . . . . . . . . . .228
6 Other Dementias and Delirium . . . . . . . . . . . . 229

Frontotemporal Dementia . . . . . . . . . . . . . . . . . . . . . . .229
Dementia With Lewy Bodies . . . . . . . . . . . . . . . . . . . . .235
Vascular Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241
Mixed Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .248
Dementia Due to General Medical Conditions . . . . . .249
Substance-Induced Persisting Dementia . . . . . . . . . . .254
Reversible Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . .255
Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .256
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .265
7 Anxiety Disorders and
Late-Onset Psychosis. . . . . . . . . . . . . . . . . . . . . 273
Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .273
Late-Onset Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . .293
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .306
8 Other Common Mental Disorders

of the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Insomnia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .313
Alcohol Abuse and Dependency . . . . . . . . . . . . . . . . . .320
Other Psychoactive Substance Abuse
and Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . .326
Sexual Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .329
Psychiatric Illness Related to a General
Medical Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . .334
Chronic Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .337
Influence of Aging on Disorders of Early Onset . . . . . .339
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .341
9 Competency and Related Forensic Issues. . . . 347

Decisional Competency . . . . . . . . . . . . . . . . . . . . . . . . .348
Undue Influence: The Question of Voluntariness . . . .358
Competency to Care for Oneself and
Manage One’s Finances . . . . . . . . . . . . . . . . . . . . . . . .360
Expert Consultation and Testimony
on Competency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .366
Competency to Drive . . . . . . . . . . . . . . . . . . . . . . . . . . .367
Elder Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .371
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .373
Appendix: Clinical Assessment

Instruments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
Geriatric Depression Scale . . . . . . . . . . . . . . . . . . . . . . .380
Six-Item Orientation-Memory-Concentration Test. . . .382
Cognistat profile: Example . . . . . . . . . . . . . . . . . . . . . . .383
Instrumental Activities of Daily Living (IADL) Scale . . .384
Revised Memory and Behavior Problems
Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .386
Items Rated on the Neuropsychiatric Inventory. . . . . .388
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
1
Introduction
An Aging World
For the first time in history, most people in societies such as our own can plan
on growing old. Life expectancy from birth has increased dramatically in the
United States, from about 47 years in 1900 to 77.3 years in 2002 (Federal In-
teragency Forum on Aging-Related Statistics 2004). Even those people who
are currently “old” can expect to live for many years. For men at age 65, aver-
age life expectancy is more than 16 years, and for women at age 65, it is almost
20 years; at age 85, men can expect to live 6 more years and women 7 years
(Federal Interagency Forum on Aging-Related Statistics 2004).
More than 20% of the current U.S. population are older than age 55, and
more than 12% are 65 or older (Federal Interagency Forum on Aging-Related
Statistics 2004). The elderly population is the only age segment of the popu-
lation that is expected to grow substantially in the next quarter century, so
that by the year 2030, one in three Americans will be age 55 or older, and one
in five will be at least age 65. Very old people (85 years and older) constitute
one of the fastest-growing subgroups of the elderly population (Figure 1–1).
In 1900, a little more than 100,000 people were age 85 years or older in the
United States, compared with an estimated 4.2 million in 2000 (National
Center for Health Statistics 2004). By 2050, there will be 19 million to 24
million people in this 85 and older age group, or nearly 5% of the total pop-
ulation. In 2003, more than 50,000 U.S. residents were 100 years or older, an
increase of 36% since 1990 (Administration on Aging 2004).
1
2 Clinical Manual of Geriatric Psychiatry
100
80
60
Population
(millions)
65 and older
40
85 and older
20
0
1900 1930 1960 1990 2020 2050
Projected
Figure 1–1. Populations of older adults in the United States (in millions).
Source. Adapted from Federal Interagency Forum on Aging-Related Statis-
tics 2004.
Worldwide, average life expectancy has increased to about 65 years (Cohen

2003), and by 2050, the number of people age 65 years and older is projected
at 2.5 billion worldwide (20% of the total population) (Olshansky et al. 1993).
Substantial increases in elderly populations are projected in the next quarter
century for North America, Europe, Asia, Latin America, and the Caribbean,
with smaller increases expected for areas such as sub-Saharan Africa, where both
fertility and mortality rates are high. China alone is expected to have 270 mil-
lion persons age 65 and older—nearly the total current population of the
United States—by the middle of this century. As one demographer recently
pointed out, the twentieth century may well be the last in which younger people
outnumbered older ones (Cohen 2003). By 2050, there will be more than three
adults age 60 years or older for every child age 4 years or younger.
Introduction 3
Health and Functioning of Older Adults

Most people age 65 and older have at least one chronic medical illness, and
many have multiple conditions. The most common illnesses affecting elderly
people in the United States are arthritis, hypertension, and heart conditions
(Figure 1–2). Sensory impairments are also prevalent. Of 65- to 74-year-olds,
30% report problems seeing and 18% report problems hearing; these rates are
approximately twice as high for persons age 85 and older (Federal Interagency
Forum on Aging-Related Statistics 2004). Each of these conditions can limit
independent function and detract from quality of life. Being overweight or
obese has increased dramatically among older Americans in recent years. The
percentage of 65- to 74-year-olds who were overweight rose from 57% to
73% between 1976 and 2002, and the obesity rate increased from 18% to
36% (Federal Interagency Forum on Aging-Related Statistics 2004). By con-
trast, rates of cigarette smoking declined by 2002 to 10% among older men
and have remained steady in recent years at about 9% among older women.
Heart disease, cancer, and stroke account for two of every three deaths among
the elderly and also account for many doctor visits and days of hospitalization.
Death rates due to heart disease and stroke decreased by approximately one-third
from 1981 through 2001, whereas death rates due to diabetes and chronic lower
respiratory diseases increased by 43% and 62%, respectively (Federal Interagency
Forum on Aging-Related Statistics 2004). Alzheimer’s disease ranked sixth, after
heart disease, cancer, cerebrovascular diseases, respiratory diseases, and influenza
or pneumonia, among causes of death for Americans age 65 years and older in
2002 (National Center for Health Statistics 2004).
In 2002, people age 65 and older were hospitalized more than three times
as often as those ages 45–64, and they remained in the hospital about a day
longer on average than did middle-aged adults (Administration on Aging
2004). Older adults visited their physicians six to seven times per year on av-
erage, compared with three to four times for 45- to 64-year-olds.
In 1999, about 20% of older adults were chronically disabled as a result
of health problems; about 3% had limitations in only higher-order activities
of daily living (e.g., financial management, transportation, medication sched-
ules), 6% had impairment in one or two basic activities of daily living (e.g.,
eating, bathing, toileting), another 6% were impaired in three to six basic ac-
tivities, and slightly fewer than 5% were institutionalized (Federal Inter-
100
80
Americans age ≥65 (%)
Men Women
60
40
20
0
Heart Hyper- Stroke Emphy- Asthma Chronic Cancer Diabetes Arthritic
disease tension sema bronchitis symptoms
Figure 1–2. Percentage of people age 65 and older with selected chronic
conditions, 2001–2002.
tics 2004.
agency Forum on Aging-Related Statistics 2004). Of disabled older people
living in the community, 66% received informal care only, generally from rel-
atives; 26% received a combination of formal and informal services; and 9%
had formal care only (Federal Interagency Forum on Aging-Related Statistics
2004). The proportion receiving paid care has increased since the early 1980s,
reflecting improved financial resources of older persons as well as liberaliza-
tion in coverage rules under Medicare and Medicaid. Figure 1–3 shows age
trends in independent and assisted living within the United States.
Those with chronic needs that cannot be met at home generally receive care
in nursing homes. Although fewer than 5% of elderly Americans are in nursing
homes at a given time, the proportion of older persons requiring such care in-
creases quite sharply with age (see Figure 1–3). Among persons who reached
their 60th birthday in 1990, more than one-half of the women and one-third
of the men are expected to enter a nursing home at some point in the future.
However, older black Americans and elders from other minority groups use
Introduction 5
1
100 5
1
5 Long-term-
2 3
19 care facility
Medicare enrollees (%)
80 7
Community housing
with services
60 93
98
92
Traditional
74
40 community
20
0
≥65 65–74 75–84 ≥85
Age (years)
Figure 1–3. Percentage of Medicare enrollees age 65 and older, by type of

residence, 2003.
tics 2004.
paid in-home services and nursing home care less frequently than do white
Americans (National Center for Health Statistics 2004). Between 1985 and
1999, the percentage of older adults residing in nursing homes in the United
States declined slightly, from 5.4% to 4.3%, but the total number of older nurs-
ing home residents increased from 1.3 million to 1.5 million because of growth
in the older population (Federal Interagency Forum on Aging-Related Statistics
2004). Three-fourths of current nursing home residents are women.
Health care costs for older Americans increased substantially from 1992
through 2001, after adjustment for inflation. During this time span, the pro-
portion of health care dollars spent on acute hospital care decreased, while the
proportion spent on prescription drugs increased. The average cost of provid-
ing health care for persons age 65 or older is currently three to five times
greater than health care costs for younger persons (Centers for Disease Con-
trol and Prevention 2004). Long-term-care costs, including nursing home
and home health expenditures, doubled between 1990 and 2001, a trend
shared by other developed nations. In 2001, the average annual cost for el-
derly residents of long-term-care facilities in the United States was $46,810,
compared with $8,466 for community residents of comparable age (Federal
Interagency Forum on Aging-Related Statistics 2004). Total Medicare spend-
ing increased from $33.9 billion in 1980 to $252.2 billion in 2002 and is pro-
jected to grow to twice that amount by 2012 (Centers for Disease Control
and Prevention 2004).
These trends present a significant challenge to the health care community.
The need to learn about aging and older people extends throughout the med-
ical and mental health professions. Creative approaches are required to stem
rising costs while maintaining quality assessment and intervention. Alliances
with families and other natural supports must be formed to ensure continuity
of care, and the strengths of older patients themselves must be marshaled to
cope with illness and to interact effectively within the health care system.
Mental Disorders in Later Life

Older people with mental disorders constitute a significant subgroup of the
elderly population. The multisite Epidemiologic Catchment Area (ECA)
Study conducted in the 1980s (Robins and Regier 1991) found that nearly
20% of Americans age 55 and older had diagnosable mental disorders, in-
cluding dementia (U.S. Public Health Service 1999). The ECA findings are
believed by many experts in the field to be underestimates because of meth-
odological limitations in the ECA assessment procedures. A 1999 consensus
conference on geriatric mental health estimated the prevalence of psychiatric
disorders in community-residing older adults at 25% or more (Jeste et al.
1999). Rates of mental disorder are much higher among elderly patients seen
in primary care or hospitalized for medical conditions, 30%–50% of whom
have psychiatric conditions (Borson and Unützer 2000; Rapp et al. 1988);
and in long-term-care settings, 68%–94% of residents have been found to
have mental disorders (Hybels and Blazer 2003). Table 1–1 compares rates for
several different types of mental disorders in the ECA community-based sur-
vey (1-month prevalence data) with a survey of hospitalized geriatric patients
conducted at about the same time. Overall, it is reasonable to estimate that
15%–25% of Americans who are currently age 65 or older have significant
mental health problems.
Introduction 7
Older patients experience the same broad spectrum of mental disorders as

do younger adults. However, certain conditions are particularly notable in later
life because of either increased prevalence or high morbidity (see Table 1–1).
The elderly are at much greater risk for cognitive impairment than are
younger adults. In the community, at least 5% of people age 65 years or older
have prominent cognitive deficits, compared with fewer than 1% of people ages
18–64 (Regier et al. 1988). A larger proportion of older people have mild cog-
nitive problems, with estimates varying widely depending on the procedures
used to assess impairment (see Chapter 2, “Normal Aging”). The numbers in
Table 1–1 may underestimate the extent of problems related to cognitive defi-
cits, especially in the oldest age ranges. Recent data from the national Health
and Retirement Study showed that among Americans age 85 and older residing
in the community, one-third had moderate to severe memory impairment (Ad-
ministration on Aging 2004), and a widely cited epidemiological survey in the
East Boston area reported a prevalence of 47% for Alzheimer’s disease alone
among community residents age 85 and older (Evans et al. 1989).
Cognitive deficits in older patients have many different possible causes,
and in many cases, treatment of underlying problems can substantially allevi-
ate cognitive symptoms or slow the course of further decline (see Chapter 5,
“Dementia and Alzheimer’s Disease,” and Chapter 6, “Other Dementias and
Delirium”). Even for individuals with dementia of the Alzheimer’s type, gains
in functional ability can be obtained by treating coexisting medical or psychi-
atric illnesses. These small gains can make a great difference to family mem-
bers caring for these patients, as can support, psychotherapy, and respite
provided for caregivers.
Depression is an equally important condition in older adults. In the com-
munity, the percentage of older people meeting strict diagnostic criteria for
major depression is generally estimated at 5% or less (U.S. Public Health Ser-
vice 1999). However, traditional diagnostic criteria may not do justice to the
prevalence of depressive symptoms among older people. Serious depressive
symptoms were found in 8%–20% of elderly community residents and in up
to 37% of the elderly in primary care settings (U.S. Public Health Service
1999). In acute-care hospitals, as many as 25% of older patients have diag-
nosable mood disorders (e.g., Rapp et al. 1988), and nearly 50% of the ad-
missions of older adults to psychiatric hospitals are for depressive conditions.
The presence of comorbid depression or anxiety greatly increases health care
costs for patients in primary care (Simon et al. 1995), and over time, depres-
sion is associated with decrements in function and well-being that are similar
to, or greater than, those associated with chronic medical disease (Hays et al.
1995). Geriatric depression can be treated effectively with standard therapies
in 60%–80% of cases (U.S. Public Health Service 1999), but it is unlikely to
resolve spontaneously. Depression, anxiety, and alcohol and drug abuse in the
elderly today are only about one-quarter to one-third as common as among
middle-aged persons, and as the 55 million baby boomers grow old, their
mental health needs may prompt a crisis in geriatric care (Jeste et al. 1999).
Many older people without major mental disorders experience adjust-
ment reactions to personal stresses, bereavement, pain syndromes, and sleep
disturbance. Education and interventions directed at these problems may pre-
vent more serious psychiatric or medical problems from developing. The im-
portance of increasing prevention efforts for older adults as well as other age
groups was underscored in the U.S. surgeon general’s report on mental health
(U.S. Public Health Service 1999).
For psychiatrists, therefore, it is important not only to identify and treat
specific psychiatric disorders but also to provide education, support, and pre-
ventive interventions to strengthen older people and their families in manag-
ing common stresses of aging.
Barriers to Geriatric Mental Health Care

Improvements have been made since the early 1990s in the detection and
treatment of mental disorders in older adults in the United States. In an anal-
ysis of national Medicare fee-for-service data, for example, rates of diagnosed
depression in older adults increased from 2.8% in 1992 to 5.8% in 1998, and
two-thirds of those diagnosed received treatment of some type (Crystal et al.
2003). Similarly, since passage of the Omnibus Budget Reconciliation Act in
1987, efforts have been made, with varying degrees of success, to recognize and
treat mental disorders in patients in skilled nursing facilities. The number of
effective antidepressant medications has increased (Chapter 4, “Mood Disor-
ders—Treatment”), and medications to slow the course of common progres-
sive dementias have been introduced (Chapter 5, “Dementia and Alzheimer’s
Disease,” and Chapter 6, “Other Dementias and Delirium”). The usefulness
of psychotherapeutic interventions for common mental disorders of older
Introduction 9
Table 1–1. Mental disorders among older adults

Distribution of psychiatric diagnoses (%)
Medical-surgical
Category of illness Community residentsa inpatientsb
Cognitive impairment 4.9 30.2

Affective disorders 2.5 18.5
Anxiety disorders 5.5 5.2
Alcohol abuse or 0.9 2.6
dependence
Schizophrenic disorders 0.1 0
Somatization 0.1 0
Personality disorder 0 8.3
Other psychiatric disorder 0 7.9
aAdapted
from Regier et al. 1988.
b
Adapted from Rapp et al. 1988.
adults has been more thoroughly confirmed (Chapters 4 through 8, “Mood

Disorders—Treatment,” “Dementia and Alzheimer’s Disease,” “Other De-
mentias and Delirium,” “Anxiety Disorders and Late-Onset Psychosis,” and
“Other Common Mental Disorders of the Elderly,” respectively), as have the
complex relationships between mental disorders and medical illness.
Despite these improvements, significant inequities remain in identifica-
tion and treatment of mental health conditions in older people and in acces-
sibility and use of geriatric mental health services (Areán and Unützer 2003;
Charney et al. 2003; Moak and Borson 2000). Adults older than 75, minor-
ity group members, and persons with Medicare only were less likely than
younger, white, and better-insured patients to have received treatment for
depression in recent years (Crystal et al. 2003), and even the most recent
studies continue to show that most cases of cognitive impairment without
obvious dementia go undetected and untreated in primary care (Chodosh et
al. 2004; Ganguli et al. 2004). Less common or less widely publicized con-
ditions are even more likely to remain unrecognized and inadequately
treated. In nursing homes, psychiatric services are generally restricted to a
consultative, as-requested mode instead of being a consistent and integrated
part of care management teams, and in the burgeoning numbers of assisted-
living and community-based programs for senior care, mental health services
are patchy and largely unregulated (Moak and Borson 2000).
Contemporary older Americans report less past use of mental health ser-
vices than do younger adults, and older Americans are less likely to express a
need for such services (Klap et al. 2003; Wetherell et al. 2004). Older adults
most often turn to primary care providers for help with mental health problems
(Kaplan et al. 1999), and typically, only one-half or fewer follow through with
referrals to specialty mental health providers. In a recent multisite randomized
trial, elderly primary care patients who screened positive for depression, anxiety,
or increased risk of alcohol use problems were offered collaborative mental
health services within primary care or enhanced referral assistance (e.g., sched-
uling, transportation, and payment assistance to outside mental health special-
ists) (Bartels et al. 2004). A significantly higher percentage of the patients
followed through on pursuing mental health treatment when it was available
within primary care (71% vs. 49%), and they completed more mental health
visits overall, than did those referred to mental health clinics or specialists, even
with enhanced assistance aimed at increasing the odds of compliance with the
referral. As the baby boom generation edges into the geriatric age range, the
“stiff upper lip” approach to managing emotional distress (Wetherell et al.
2004) may change, but the desire for proximal, integrated medical and mental
health services is likely to continue. Without more effective collaborative care,
underrecognition of mental health problems, especially among older patients
(Young et al. 2001), is likely to continue for several reasons:
• Multiple medical illnesses in elderly patients may divert physicians’ attention

away from psychiatric signs and symptoms, especially within the time-pres-
sured context of the standard brief office visit.
• Depression, anxiety, or memory problems may be viewed as normal for
older people with serious medical illness.
• Physicians with neither psychiatric nor geriatric training may have difficulty
distinguishing normal aging changes from signs of mental disorder or may
be reluctant to “open the can of worms” that treatment of emotional or cog-
nitive problems may entail.
A probability survey of primary care providers found that only 6% of gen-

eral internal medicine physicians and 22% of family practice physicians used
Introduction 11
questionnaires or other structured procedures to screen for depression in their

older patients, relying instead on very brief informal interviews (Kaplan et al.
1999). Primary care physicians report that the subtlety of mild dementia
makes it difficult to recognize during brief interviews, but many physicians
remain reluctant to use formal cognitive screening tests (Boise et al. 1999);
many also believe that in the absence of effective treatment, there is little pur-
pose to diagnosing mild dementia, although this attitude may delay arrange-
ments for community support services and increase family strain (see Chapter
5, “Dementia and Alzheimer’s Disease”).
Among psychiatrists, attitudes about aging and age-related conditions
and limited training in geriatric psychiatry may further restrict the availability
and quality of mental health care for older patients. Many psychiatrists and
other mental health professionals find it difficult to work with elderly pa-
tients. Understandably, they may prefer to work with patients who have less
daunting problems with physical illness and personal loss, who remind them
less of their own mortality, and who are less likely to die in the course of treat-
ment. Nonetheless, recent research has not found mental health professionals
to be strongly or pervasively negative in their attitudes about older patients.
Instead, age bias seems to take more specific forms (Gatz and Pearson 1988).
American psychiatrists and other mental health professionals tend to refer
older patients less often for psychotherapy than comparably ill younger pa-
tients, and some of these professionals, in an attempt to avoid discrimination
against the elderly, may exaggerate the competencies and excuse the deficits
of elderly patients. “Fallacy for good reasons” is a phrase coined to refer to the
common situation in which a provider, as well as the patient and family mem-
bers, attributes the depression or anxiety experienced by the older patient to
medical illness, multiple losses, or financial difficulties that many older per-
sons face, especially the very old (Cole et al. 1997).
Inadequate insurance coverage for patients and limited reimbursement
for providers are ongoing barriers to geriatric mental health care. Because pre-
scription drugs have not been covered under Medicare until very recently, el-
ders who could not afford a coinsurance policy with drug benefits were
unable to afford psychiatric medications. The 50% copayment rule for psy-
chotherapy services under most insurance policies makes the decision to en-
gage in therapy costly to the patient, and allowable fees are often inadequate
(e.g., under Medicare, the psychotherapy fees allowed for an experienced psy-
chiatrist are half or less of the typical fee expected for this service). The elderly,
who generally have many health care needs, often have trouble coordinating
their own care, but there is usually no reimbursement for mental health pro-
viders to help with coordination.
The need for psychiatrists who are capable and willing to work with el-
derly patients, both in primary care and in specialty roles, is clear. Effective
models for collaborative medical and mental health services recently have
been developed for primary care (see Chapter 4, “Mood Disorders—Treat-
ment”), but this approach needs to be extended beyond clinical research, and
additional models need to be developed for geropsychiatric services within
community mental health settings and the full spectrum of long-term-care
services (Moak and Borson 2000). Older adults with medical comorbidity,
the oldest old, and those with significant chronic mental illness present par-
ticular challenges to existing service models (Borson et al. 2001).
Diversity in Patterns of Health and Aging

In 2003, persons of minority descent, including Hispanic whites, accounted
for 17.6% of the U.S. population age 65 and older, but by 2050, this percent-
age is projected to rise to 36%. Hispanic and Asian American groups as a
whole are the most rapidly growing minority populations, and these trends
are projected to continue (Figure 1–4).
Methodological difficulties encountered in the processes of sampling, de-
signing valid interview protocols, achieving subject cooperation, and control-
ling interviewer and subject bias have hampered attempts to generalize about
the health and other characteristics of black, Hispanic, American Indian, and
Asian populations in the United States. However, in key areas such as life ex-
pectancy, prevalence of chronic health conditions, residential patterns, and
education, significant differences have been documented across groups. In the
United States in 2001, average life expectancy from birth was 5.5 years longer
for white persons than for black Americans (Federal Interagency Forum on
Aging-Related Statistics 2004). At age 65, however, the life expectancy gap
narrowed to about 2 years, and by age 85, life expectancy was slightly longer
for older black persons compared with white persons. In 2000–2001, among
people age 65 and older, hypertension and diabetes were more common
among black than among non-Hispanic white persons; older Hispanics were
Introduction 13
100
2003
80
2050–projected
60
40
20
0
Non-Hispanic Black alone Asian alone All other races alone Hispanic
white alone or in combination of any race
Figure 1–4. Percentage of population age 65 and older, by race and His-
panic origin.
tics 2004.
comparable to non-Hispanic white Americans in rates of hypertension but
were more likely to have diabetes. By contrast, older white people were more
likely to have some form of cancer than were older Hispanic or black people
(National Center for Health Statistics 2004). Black and Hispanic elders are
less well educated than non-Hispanic white and Asian elders (see Figure 2–1
in Chapter 2, “Normal Aging”), and older black and non-Hispanic white per-
sons are more likely to find themselves living alone in old age than are their
Hispanic or Asian peers (see Figure 2–2 in Chapter 2).
Reports of prevalence of mental disorders for minority groups must be
viewed with caution because language and cultural differences can affect re-
sults on tests and interviews assessing depression, dementia, and other psychi-
atric disorders. However, data are emerging on the relative prevalence of
mental health–related problems in various groups and on availability and use
of mental health services. A recent supplement (U.S. Public Health Service
2005) to Mental Health: A Report of the Surgeon General (U.S. Public Health
Service 1999) concluded that the prevalence of mental disorders within the
most populous racial and ethnic minority groups in the United States (blacks,
Hispanics, and Asian Americans and Pacific Islanders) is similar to that of
white Americans. Among older adults, however, some important differences
in prevalence of mental health–related conditions have been documented for
racial/ethnic and gender subgroups. For example, the suicide rate is much
higher among non-Hispanic white men than in any other elderly subgroup
(National Center for Health Statistics 2004), and rates of alcohol abuse and
dependence are higher among elderly black men and women compared with
elderly white and Hispanic persons (U.S. Public Health Service 1999).
The surgeon general’s recent supplement underscored the pivotal role of
culture in maintaining mental health and the continuing, often striking, dis-
parities in availability of and access to mental health services among Ameri-
cans from minority backgrounds. Although not specific to older adults, the
recommendations for reducing barriers are as important for diverse geriatric
populations as they are for younger groups. The recommendations include
the following:
• Continuing research to establish the efficacy of evidence-based treatments

for racial and ethnic minorities and to better characterize how factors such
as acculturation and ethnic identity affect risk for, and protection from,
mental illness
• Improving access to treatment by improving geographic distribution of
services, increasing availability of services in preferred languages, and co-
ordinating care for the most vulnerable, high-need subgroups in which
racial and ethnic minorities are overrepresented (e.g., low-income or
homeless persons)
• Delivering effective, evidence-based treatments that are individualized ac-
cording to age, gender, race, ethnicity, and culture
• Working toward equitable racial and ethnic representation among mental
health providers, administrators, and policy makers
Women constitute the majority of older persons in the United States, out-
numbering men by a ratio of nearly 3 to 1 by age 85 and older. Important
gender differences have been reported for longevity, prevalence of specific
Introduction 15
Table 1–2. Knowledge needed to work effectively with elderly

patients
Normal aging: biological, psychological, and social changes
Mental disorders predominantly observed in later life, including Alzheimer’s disease,
related dementias, late-onset psychoses
Effects of age on other psychiatric disorders, including mood and anxiety disorders
Adjusting psychiatric treatments for aging changes: dose and schedule of
psychoactive medications, drug-drug interactions, format and pace of
psychotherapy
Managing social and physical problems of later life: bereavement, role loss, pain,
sleep disturbance
Interactions of psychiatric and medical-surgical illnesses and their treatments
medical or mental conditions (e.g., heart disease, Alzheimer’s disease), and

rates of disability. At present, the price that women pay for longer lives ap-
pears to be a greater proportion of the late life span compromised by func-
tional disability, limited options for home care, and an increased likelihood of
spending their last years in a nursing home. Recent research, prompted by the
Women’s Health Initiative, is helping to elucidate whether preventive health
care, or more prompt and appropriate diagnosis and treatment of medical
conditions, can reduce the functional limitations now experienced dispropor-
tionately by women in later years.
Working Effectively With Older Adults

Psychiatric care of older patients requires a blending of specialized knowledge
with a broadly based, flexible approach to the patient (Table 1–2).
In addition to mastering the content areas covered in this Clinical Man-
ual, a psychiatrist treating older patients needs certain personal qualities and
professional approaches that are important for effective work in geriatric psy-
chiatry (Table 1–3). Although some older people can manage today’s complex
health care system, many more lack the energy, sophistication, cognitive abil-
ity, or funds to negotiate a specialty-oriented system successfully. As a result,
psychiatrists working with older people must be willing to play a generalist
role, combining routine medical management with psychiatric interventions
or helping with specific social or situational problems.
Table 1–3. Personal qualities and professional approaches

needed to work effectively with elderly patients
Willingness to provide broadly based, flexible management
Comfort in working closely with other health care professionals
Patience and skill in providing medical information and assisting in medical decision
making
Willingness to explore one’s own feelings about aging
Openness to discuss patients’ concerns about being treated by younger professionals
Acceptance of and comfort with limited treatment goals
Ability to maintain therapeutic optimism in the context of an ultimately poor
prognosis
The psychiatrist also must have patience and skill in explaining diagnoses
and treatments and in assisting older people in medical decision making. El-
derly patients often defer to physicians without truly comprehending benefits
and risks. This deference may increase efficiency of care in the short run, but
it may place the older person at risk for iatrogenic illness (e.g., delirium sec-
ondary to drug interactions). Finally, it is helpful to have a willingness to ex-
plore one’s own feelings about aging, as well as to be open to discussing older
patients’ reservations about the wisdom of youth. Elderly patients may be in-
clined to view younger therapists as similar to their children, and the thera-
pist, in response, may experience the reactivation of unresolved conflicts with
parents or grandparents or unresolved issues related to his or her own personal
aging (Meador and David 1994).
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Introduction 17
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Introduction 19
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2
Normal Aging
Conceptual Issues
Who Is Old?
Biological and psychological aging changes usually occur gradually, over years or
decades, and as a result, there is no single age at which people in general can be
said to be old. The common practice of designating people older than 65 as “old”
began in Germany in the 1880s, when Otto von Bismarck selected 65 as the start-
ing age for certain social welfare benefits. In the United States, the age at which
full Social Security benefits can be received has now been raised to 67 years for
persons born in 1960 and later. Although this change is primarily a response to
fiscal concerns, the upward shift is also indicative of the increasing vitality and
productivity of the aging population. According to a recent national survey, 63
years is the average age at which Americans perceive individuals as becoming old,
but there was much variation in perceptions (Abramson and Silverstein 2004).
More than one-third of the sample named an age greater than 70 as the start of
old age, whereas another one-fourth cited ages less than 60 years.
Gerontologists often draw finer chronological demarcations within the
general group of aging persons. Comparisons may be made between the young-
old and the old-old (generally, those younger than and older than age 75, respec-
tively) or between these groups and the oldest old (generally 85 years and older).
Although these distinctions are also arbitrary, they can be useful in identifying
important differences in levels of functioning and can help to limit overgener-
alization about characteristics of older adults. It is also important to keep in
21
mind that individuals may age faster in some dimensions than others (e.g.,
being “old” physically but more youthful psychologically or socially).
Cross-Sectional and Longitudinal Views

The most common way to study the effects of aging is to compare a group of
older people with a separate group of younger adults. Because generational
differences in education, health practices, diet, and other important factors
are confounded with age differences when young and old subjects are com-
pared, cross-sectional investigations often provide an inflated estimate of the
magnitude of aging changes that will occur in individuals.
Longitudinal designs also have been used to study normal aging. These
investigations track the same individuals over years, or even decades. The least
healthy and able subjects are often the first to drop out from these samples,
so longitudinal investigations may provide an overly optimistic estimate of
the extent of decline with age.
The best picture of normative aging trends is obtained from studies in
which multiple cohorts are assessed longitudinally or by combining the re-
sults of separate cross-sectional and longitudinal studies. The Seattle Longi-
tudinal Study conducted by Werner Schaie (2005) and colleagues provides
one of the best examples of a multiple-cohort longitudinal aging study, out-
comes of which have helped to shape understanding of cognitive processes
that remain stable or reliably decline with age. At least 25 other longitudinal
investigations of behavioral aspects of aging are ongoing at this time, and a
burgeoning number of cross-sectional studies are being done.
Heterogeneity in Patterns of Aging

On many psychological and biological measures, variability is greater in old-
age samples than among younger adults. A longitudinal study of 426 elderly
community dwellers by Christensen and associates (1999) found increases in
interindividual variability with age in memory, spatial functioning, and speed
but not in crystallized intelligence. Being female, being more depressed, being
more ill, and having weaker muscle strength were associated with greater vari-
ability, whereas having a higher level of education was associated with reduced
variability. Pronounced variability decreases the sensitivity in upper age ranges
of many measures that are used to infer pathological changes and casts doubt
on the search for singular normative aging trends. Many different normal ag-
Normal Aging 23
ing trajectories may exist, with varying trends for different genetic and socio-
cultural subgroups. Intraindividual variability (i.e., fluctuating performance
within and across assessments) is also increased in old age, especially for cog-
nitive and physical performance measures. Heightened variability within the
individual has been linked to an accelerated rate of cognitive decline over time
and may be a marker for neurobiological aging (MacDonald et al. 2003).
Cognitive Abilities in Later Life: A Processing

Resource Model
Cognitive changes with aging are well documented and affect a broad range
of functions (see the subsection “General Aging Trends” later in this section).
However, many of the differences in specific abilities can be traced to declines
in three fundamental cognitive-processing resources: the speed at which in-
formation can be processed, working memory, and sensory and perceptual
skill (Park 1999).
Processing Speed
Perhaps the most predictable of all cognitive changes is the reduced speed of
information processing and response. Slowed execution of component per-
ceptual and mental operations can affect attention, memory, and decision
making and can influence performance even on tasks that have no obvious
speed requirements (Salthouse 1996).
Working Memory
Working memory refers to short-term retention and manipulation of informa-
tion held in conscious memory, a type of “online” cognitive processing (Bad-
deley 1986). Examples include consciously recalling a telephone number long
enough to write it down, mentally calculating the sale price of an item that is
reduced by 15%, and mentally traversing a route that one intends to walk or
drive. Information fades from working memory within about 2 seconds, so to
keep details “alive” for a longer time requires active rehearsal or continuing re-
focusing of attention.
Aging is associated with a decline in working memory skills, especially
when active manipulation of information is required (e.g., repeating numbers
backward as opposed to forward). Reductions in working memory, in turn,

place limits on other complex cognitive skills, including reasoning and other
executive processes, and learning and recall of new information.
Sensory and Perceptual Changes

Most older adults experience decrements in visual and auditory acuity and
other perceptual changes. Some, but not all, of the age-related visual changes
can be corrected by glasses, and although hearing aids help with detection of
low-frequency tones, they often amplify background noise. In effect, many
older adults find it hard to hear or see well, especially with competing back-
ground noise and poor lighting conditions.
Recent studies suggest a strong correlative link between sensory and per-
ceptual changes and cognitive performance in old age. Younger adults tested
with degraded perception (e.g., by background noise or reduced visual con-
trast) perform much like older adults on measures of learning, memory, and
language (Schneider and Pichora-Fuller 2000). The extra time and effort re-
quired to process information necessitated by sensory and perceptual prob-
lems tax working memory, effectively overloading the system.
The combined effects of central nervous system slowing, reduced working
memory, and sensory and perceptual changes limit the processing resources that
older persons can bring to bear in particular situations. These changes increase
the likelihood of processing overload in circumstances that may have once pre-
sented little challenge. In advanced old age, even basic activities such as walking
or maintaining postural control become less automatic, with the result that
older persons must devote more conscious cognitive resources to these activities.
Neuropsychological Explanations of Cognitive Aging

Changes
Neuropathological and neuroimaging studies have documented widespread
changes in the human brain with aging (Raz 2000; Victoroff 2000). There are
generalized atrophic and white matter changes as well as region-specific vari-
ations in the extent of cell loss. Within the cortex, the prefrontal lobes are
disproportionately affected by aging changes, whereas temporoparietal asso-
ciation areas are less affected. Subcortical monoaminergic cell populations,
which connect to the frontal lobes by a complex network of projections, are
also subject to prominent decline in aging. Data are more conflicting regard-
Normal Aging 25
ing changes in the hippocampus and entorhinal cortex, with some studies
noting minimal cell loss with normal aging in these regions and others show-
ing decremental changes. Areas in which there is relative sparing with age in-
clude the globus pallidus, the paleocerebellum, the sensory cortices, and the
pons (Raz 2000).
Some of the behavioral changes in aging, such as slowed information pro-
cessing and response, may be related to generalized changes such as decreased
brain volume and white matter density. Other changes appear to mirror the se-
lective pattern of differential change in prefrontal cortical structures and striatal
dopaminergic nuclei. Decreased working memory, problems with effortful
learning and recall, and changes in efficiency of executive functions are some of
the findings that suggest a mild degree of frontal or subcortical brain dysfunc-
tion in normal aging (Prull et al. 2000). The “frontal lobe hypothesis” is perhaps
the most popular neuropsychological model of normal aging at this time. How-
ever, hippocampal changes also may play a role in normal aging memory. Hip-
pocampal volume, as measured by magnetic resonance imaging, correlates with
memory performance in older adults, and those with smaller hippocampal vol-
umes are at greater risk for developing dementia. What remains to be resolved,
however, is whether reduced hippocampal volume is truly within the normal
aging spectrum or instead is a preclinical phase of dementia.
Functional neuroimaging studies have shown less regional specificity in
older adults’ patterns of brain activation to various cognitive tasks compared
with the regional specificity in young adults (Prull et al. 2000; Raz 2000). One
interpretation of this finding has been that older persons must recruit more
neural systems to perform even relatively simple mental operations. This inter-
pretation coincides in a general way with the behavioral model of reduced pro-
cessing resources and increased susceptibility to overload on complex tasks.
General Aging Trends

Table 2–1 summarizes general aging trends for intelligence and specific areas
of cognitive function. In this table, mild decline refers to changes that are generally
within a standard deviation of the mean for young adults, whereas moderate de-
cline refers to differences on the order of one to two standard deviations below the
average for young adults. As the table indicates, cognitive changes associated with
normal aging generally fall within the mild to moderate range, and there are some
areas in which performance remains stable or improves. The differential pattern
Table 2–1. Aging effects on cognitive performance

Ability Direction of aging change Comment
Intelligence
Vocabulary, fund of Stable or increasing May decline slightly in very old age; most pronounced on novel
knowledge tasks
Perceptual-motor skills Declining Decline begins by ages 50–60
Attention
Attention span Stable to mild decline
Complex attention Mild decline Problems with dividing attention, filtering out noise, shifting
attention
Language
Communication Stable In absence of sensory impairment
Syntax, word knowledge Stable Varies with education
Fluency, naming Mild decline Occasional word-finding lapses
Comprehension Stable to mild decline Some erosion in processing complex messages
Discourse Variable May be more imprecise, repetitive
Memory
Short-term (immediate) Stable to mild decline Forward digit span intact (7±2 items), but easily disrupted by
interference
Working Mild to moderate decline Reduced ability to manipulate information in short-term
memory
Secondary (recent) Moderate decline Encoding and retrieval deficits; storage intact
Table 2–1. Aging effects on cognitive performance (continued)
Ability Direction of aging change Comment
Memory (continued)
Implicit Stable to mild decline May recall incidental features more easily than consciously
processed information
Remote Variable Intact for major aspects of personal history
Prospective Variable Mild to moderate decline on laboratory tasks, but older adults
often outperform younger people on naturalistic prospective
memory tasks
Visuospatial
Design copying Variable Intact for simple but not complex figures
Topographic orientation Declining Most noticeable in unfamiliar terrain
Executive functions
Cognitive flexibility Mild to moderate decline Slower and less accurate in shifting from one thought or action
to another
Logical problem solving Declining Some redundancy and disorganization
Practical reasoning Mild to moderate decline Qualitatively intact, but reduced efficiency on complex or novel
Normal Aging
tasks
Speed Declining Slowing of thought and action is the most reliable aging change
27
of abilities shown in Table 2–1 is less apparent among the oldest-old (e.g., 85 or
older), for whom some studies report a generalized pattern of gradual decline. An-
other important qualification concerns secular trends in levels of performance. In-
tellectual performance scores have been increasing over the past few decades, and
the rate of increase is higher among older, as opposed to younger, adults. For ex-
ample, vocabulary scores on the commonly used Wechsler Adult Intelligence
Scale (Wechsler 1997) have increased nearly 5 IQ points per decade for 65- to 74-
year-olds, compared with 1.5 points for 18- to 24-year-olds (Uttl and Van Alstine
2003). Higher absolute levels of intellectual ability may benefit contemporary
older adults in learning new information and acquiring new skills (see the subsec-
tion “Effect of Cognitive Change on Everyday Function” later in this section).
Factors That Influence Cognitive Aging

Table 2–2 summarizes characteristics and experiences that influence the de-
gree of cognitive change individuals show as they age. The cumulative effect
of these factors, operating over months or years, may be responsible for in-
creasing variability in cognitive performance at older ages. Healthy and
stimulating lifestyles, in addition to early life advantages such as adequate ed-
ucation, are hypothesized to strengthen the “cognitive reserve” that individu-
als have available to cope with neurobiological changes resulting from aging
or illness (Scarmeas and Stern 2003). Increasing evidence, for example, indi-
cates that physical and mental exercise, a healthy diet, and strong social sup-
ports may serve as protective factors against the development of dementia
(e.g., Fratiglioni et al. 2004).
Learning and Memory

When older people complain about their cognitive abilities, they usually men-
tion problems with memory. Research substantiates these complaints, but as
shown in Table 2–1, some aspects of memory decline more with age than do
others (La Rue 1992; Prull et al. 2000). Short-term or immediate memory re-
mains stable or declines to a modest degree in later life. For example, the median
forward digit span for healthy persons in their 80s is six items, compared with
seven items for persons in their 30s (Wechsler 1997). On more demanding tests
of short-term memory, such as recalling information after an interfering mes-
sage, age differences favoring the young are likely to be observed, which coin-
cides with the declines in working memory discussed earlier.
Table 2–2. Cognition in normal aging: moderating variables
Genetic factors About 50% of cognitive variability in old age can be traced to genetic factors.
Health Optimally healthy elderly persons outperform those with medical illnesses on many cognitive tests.
Education Education accounts for up to 30% of cognitive variability in old age.
Mental activity Mentally stimulating activities correlate with higher cognitive performance and reduced
longitudinal decline.
Physical activity Aerobic fitness is associated with better cognitive performance in old age.
Expertise Aging experts may develop compensatory strategies to maintain a high level of performance despite
some erosion in underlying cognitive skills.
Personality and mood Depression correlates with self-perceived memory failure and with performance impairments if
symptoms are severe.
Social and cultural milieu Everyday memory lapses may be judged more critically when experienced by older people than
by young adults.
Cognitive training Cognitively unimpaired older persons benefit from practice and training in specific cognitive skills.
Cohort effects Recently born cohorts are outperforming those born near the turn of the century on many cognitive
skills.
Sex differences Cognitive aging trends are similar for the two sexes, but women may show decrements on spatial
tasks at an earlier age than men, and men may show decrements on verbal tasks at an earlier age
Normal Aging
than women.
Racial and ethnic differences Performance differences favoring elderly white persons have been reported on some cognitive tests,
but when education is equated across groups, these differences are reduced or eliminated.
29
Anecdotally, remote or long-term memory is well maintained in old age.

Research results are not so clear, partly because remote memory is difficult to
measure because initial or intervening exposure to the material cannot be pre-
cisely controlled (La Rue 1992; Prull et al. 2000). Overall, however, older
adults’ absolute levels of performance on remote-memory tests are often im-
pressively high; for example, one study found that people recognized names
or photographs of more than 70% of high school classmates after an interval
of almost 50 years.
Another type of memory that shows minimal or modest age change is im-
plicit or incidental recall. Incidental facts or features (e.g., the color of some-
one’s dress) can be recalled with about equal accuracy by young and old,
whereas the old are more prone to forget information that they had explicitly
hoped to retain (e.g., the person’s name).
Prospective memory (i.e., memory for actions intended in the future) shows
divergent age trends, depending on how and where it is measured (Henry et al.
2004). In laboratory settings, older adults typically do less well than younger
persons. However, on naturalistic tasks (e.g., remembering to call to make an
appointment), older adults often show superior follow-through, mainly because
of more reliable use of external aids such as reminder notes.
The largest age decrements are observed in recent, episodic memory (La
Rue 1992; Prull et al. 2000). Age differences favoring the young have been
found on many explicit tests of recent memory, such as remembering items
on shopping lists, learning to associate pairs of words, copying designs from
memory, and remembering content of stories and conversations. On the av-
erage, healthy older individuals make more mistakes than young adults on
memory items from mental status examinations, such as 5-minute delayed re-
call of three or four simple words. On demanding explicit memory tasks,
older persons recall less information initially compared with young adults,
but their performance improves with repetition, and they retain most of what
they learn after delays and distractions. This ability to retain information,
once it is acquired, is one of the best ways to distinguish normally aging mem-
ory from that of patients with amnestic conditions or Alzheimer’s disease (see
Chapter 5, “Dementia and Alzheimer’s Disease”).
Some of the problems that older people have with initial learning may be re-
lated to strategies used for processing new information (La Rue 1992). Many
older people take a more passive approach to learning and remembering than do
Normal Aging 31
younger adults. For example, elderly people report less spontaneous use of mne-
monic strategies than do younger people and do not appear to capitalize as readily
on the organization inherent in words or actions as a basis for learning and recall.
The shallower memory traces that result are subsequently harder to retrieve, espe-
cially without the aid of reminders or cues. If older individuals are explicitly in-
structed to use mnemonics or organizational strategies, their learning and recall
often improve dramatically, at least in the short term.
Active encoding and retrieval may require greater expenditure of effort and
energy than most older people can afford. Declines in effortful processing may be
caused by altered neurotransmitter functions (especially catecholamines). Alterna-
tively, such processing changes may be seen as an adaptive response to the dimin-
ished demands of older adults’ everyday lifestyles. Also, it is important to note that
some healthy and active elderly people do as well on demanding recent memory
tasks as do more average young adults.
Older adults (and younger persons, too) often ask about ways to improve
their recall of everyday information. Mnemonic training can produce notable
gains in troublesome areas, such as recall of names, locations of objects, and lists
of things to be purchased or done, for old as well as young adults. Training is most
likely to be effective for young-old persons as opposed to the oldest-old and for
individuals with no decline on mental status examination (Verhaeghen et al.
1992). Training also works best in an individual or a small-group format and with
relatively short (e.g., half-hour) sessions as opposed to longer workshops or lec-
tures. Follow-up studies often show that people discontinue memory techniques
they have learned within a few weeks. In some cases, this may simply mean that
the training served its intended purpose (i.e., to prove that one can remember
more if need be), but it is also likely that the use of mnemonics may be too effort-
demanding in the long run. A greater drawback of mnemonic training ap-
proaches is that benefits often fail to generalize to everyday tasks not specifically
included in training (Ball et al. 2002). Education and counseling about memory
improvement is best approached from a broad perspective, in which improving
memory is seen as part of an overall wellness plan.
Of the many self-help books providing advice on how to maintain memory
function into old age, Keep Your Brain Young (McKhann and Albert 2002) is
among the best in terms of readability, breadth, and linkage to research. Learning
Throughout Life (National Retired Teachers Association et al. 2004) is another
good guide for the general reader. In The Memory Prescription, Small (2004) out-
lines a 2-week program of diet, exercise, stress reduction, and mental exercise de-
signed to boost brain function. The program is derived from an ongoing program
of research, but independent studies are needed to assess benefits of this approach.
Executive Function
The term executive function refers to cognitive abilities necessary for complex goal-
directed behavior and adaptation to change. Some of the skills included in this
category are reasoning, planning, anticipating outcomes of behavior, directing at-
tentional resources in a flexible manner, monitoring one’s own behavior, and self-
awareness. Performance of such skills requires the coordinated activity of multiple
regions of the brain and can be affected by injury to several different areas. How-
ever, the prefrontal cortex and frontal-subcortical brain circuits have been shown
to play a central role in executive functions. As noted earlier, normal aging has a
greater decremental effect on these brain regions than on many other areas, and
predictably, age differences are relatively large on executive function tasks (see
Table 5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for examples of
neuropsychological tests of executive function). Performance on executive func-
tion tests correlates more closely than scores on many other cognitive tasks with
activities of daily living, and changes in executive function may play a role in de-
termining which older people come to clinical attention for mild cognitive
changes (Royall et al. 2005).
Although research generally shows that older adults do worse than young or
middle-aged persons on both laboratory-based and practical reasoning tasks
(Thompson and Dumke 2005), not all studies show this trend. For example, one
recent investigation found that cognitively healthy 65- to 74-year-olds provided
more relevant solutions to problem situations—such as trying to improve the
acrimonious tone of a meeting, dealing with excessive demands by one’s sons to
babysit their children, or having blood drawn by a physician who is having diffi-
culty with the procedure—than did a comparison group of 20- to 29-year-olds
(Artistico et al. 2003). In general, interpersonal problem solving is an area of
strength for older people (Thompson and Dumke 2005).
Effect of Cognitive Change on Everyday Function

Although normal aging is accompanied by a variety of cognitive changes,
most older adults are not impaired in everyday activities, even when relatively
complex cognitive processing is required.
Normal Aging 33
Several factors help to maintain daily function in the face of mild cognitive
decline (Park 1999). The very gradual nature of age-related change allows time to
adjust to diminished speed and efficiency in cognitive function. The fact that gen-
eral knowledge is well preserved in later life allows older adults to access a broad
base of information that is useful in solving problems and addressing everyday
needs. With practice, many tasks become automatic and require little cognitive
processing or effort to perform, and maintaining a familiar environment and rou-
tine further reduces cognitive load. Also, many older adults make frequent and ef-
fective use of external cognitive aids such as writing reminder notes.
Some areas, such as driving and monitoring medications, pose particular
risks (Park 1999). Older adults are more likely to be involved in accidents while
driving than are younger persons, particularly in certain situations (e.g., left
turns in intersections). Cognitive research has identified a measure of peripheral
vision (so-called useful field of vision) that is more predictive of driving success
than are standard visual acuity measures, and this research also has found that
older adults can improve driving skill through a combination of perceptual
training and traditional drivers’ education classes (see Chapter 9, “Competency
and Related Forensic Issues,” for additional information on driving). Regarding
medications, it is important to note that some studies show better compliance
with medication regimens among older adults than among younger or middle-
aged persons, particularly if the older adults are taking only a single medication
for a long-standing condition (e.g., hypertension or arthritis). When they are
taking multiple medications that require dosing several times a day, the risk of
errors is increased, and it has been estimated that about 1% of acute hospital
admissions for older persons are precipitated by medical errors or medication
reactions.
In industrialized nations, an overabundance of new information and rapidly
changing technologies place a heavy demand on learning skills. Older adults
bring to this situation a wealth of accumulated knowledge and experience, which
can facilitate learning of new information in areas of prior knowledge. One re-
cent study found, for example, that older age proved to be an advantage in learn-
ing new information about cardiovascular disease, presumably because of older
adults’ greater baseline knowledge of health-related subjects (Beier and Acker-
man 2005). By contrast, younger adults were more adept at learning about a new
technology. Research on training methods has shown that older adults learn best
with self-paced training or other training environments that allow ample time to
assimilate the information presented (Callahan et al. 2003). These modes of ed-
ucating most effectively remediate, or compensate for, reduced speed of process-
ing and working memory or sensory limitations.
Clinical Implications of Cognitive Change

Cognitive declines that accompany normal aging complicate detection and
diagnosis of organic mental disorders. One common error is overdiagnosis of
dementia, particularly in persons with limited education. In one large multi-
cultural study, most old persons without dementia who had less than 5 years
of education were rated with standard mental status examinations as impaired
(Wilder et al. 1995).
Among healthy, well-educated old persons, brief cognitive screening may
fail to detect focal brain impairment or dementia in early stages. For example,
as many as one in three older patients with mild Alzheimer’s disease who are
otherwise healthy and have at least a high school education can be expected
to score in the normal range on very brief tests for cognitive screening.
Outcomes of cognitive mental status examinations in older people must
be interpreted cautiously, and the clinician should follow up with a more
thorough diagnostic assessment for those who score in the impaired range or
whose adequate performance on a screening examination is inconsistent with
lapses in everyday behavior. Paying attention to the pattern and types of errors
may also help to distinguish normal from abnormal cognitive changes. Chap-
ter 5 (“Dementia and Alzheimer’s Disease”) provides more specific guidelines
for screening for dementia through the use of cognitive mental status exami-
nations, and the following subsection discusses more specific diagnostic issues
concerning age-associated cognitive syndromes.
Age-related cognitive changes also have implications for the doctor-patient
relationship and for selection and monitoring of treatment. Extra care may be
required in explaining medical procedures to ensure informed decision mak-
ing. Asking the patient to repeat the main points and providing written sum-
maries or illustrations may help to make details of procedures clear, although
very complicated medication organizers or instructional charts may be coun-
terproductive.
In psychotherapy, the reduced pace of new learning and changes in rea-
soning processes may result in a slower rate of clinical improvement. Often,
this can be dealt with effectively by increasing the number of therapy sessions.
Normal Aging 35
Abrupt changes in cognitive function always warrant medical attention.

Even more gradual declines, emerging over a year or two, may be an early
warning of occult illness (so-called terminal decline) and should be carefully
monitored. According to one recent study, subclinical cognitive decline in-
creases the risk of mortality in older men as much as a history of cancer does.
Diagnosing Age-Related Cognitive Change and Mild

Cognitive Impairment
In DSM-IV-TR (American Psychiatric Association 2000) nomenclature, the
category of age-related cognitive decline (780.9) may be coded to denote
functioning of an older person with mild cognitive changes that are within
normal limits for age and not attributable to a medical disorder.
No guidelines have been developed for identifying age-related cognitive
decline. However, diagnostic criteria have been proposed for a related, but
narrower, category of age-associated memory impairment (AAMI). Persons
with a diagnosis of AAMI must be 50 years or older, have subjective com-
plaints of memory loss affecting routine activities, and perform below the av-
erage level of young adults on a standardized memory test; exclusionary
criteria include any neurological, psychiatric, or medical disorders that could
reasonably be assumed to be producing the memory change. The prevalence
of AAMI based on objective assessment has been estimated to range from
40% for persons in their 50s to 85% for those 80 and older (Larrabee and
Crook 1994). Thus, five of every six very old, healthy persons can be expected
to perform somewhat lower than young or middle-aged adults do on memory
tests and possibly to have mild memory lapses in everyday activities. AAMI
has been shown to be stable over intervals of at least 4 years; thus, it is pre-
sumed to reflect normal aging, as opposed to beginning dementia or other
brain disorder.
Clinicians are also likely to see older adults whose cognitive skills are
somewhat worse than expected for their age but who are still coping well over-
all and do not appear to have dementia. Much research has been devoted to
this gray area of performance, generally referred to as mild cognitive impair-
ment. Diagnostic criteria for this condition are still evolving, and several def-
initions have been proposed (see Winblad et al. 2004).
The skill most commonly affected in mild cognitive impairment is learn-
ing and recall of new information, but in some cases, problems are noted in
other cognitive areas, such as language, visuospatial skills, or reasoning. The

term amnestic mild cognitive impairment is used when memory is impaired,
and the term nonamnestic mild cognitive impairment is used for other types of
mild cognitive deficits. Additional subcategorization has been proposed to
distinguish between cases in which a mild deficit is observed in a single do-
main (e.g., memory) or in multiple domains (e.g., memory and reasoning).
In all forms of mild cognitive impairment, there may be subtle difficulty with
higher-order activities of daily living such as financial management, but this
difficulty is often intermittent and can be dealt with by extra effort or com-
pensatory approaches such as note taking or double-checking one’s work.
Table 2–3 compares diagnostic criteria for amnestic mild cognitive impair-
ment with those for AAMI.
The very short tests included in mental status examinations are generally
not sensitive to mild cognitive impairment, and if this condition is suspected,
referral for neuropsychological testing is recommended. To improve screening
accuracy for amnestic mild cognitive impairment, a more challenging test of
learning and memory should be incorporated into the psychiatric examina-
tion (see Table 5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for
examples of memory tests). DSM-IV-TR research criteria for mild neurocog-
nitive disorder (coded as cognitive disorder not otherwise specified, 294.9)
may be appropriate for some cases of mild cognitive impairment (i.e., when
there is mild cognitive dysfunction in two or more areas, and when deficits
do not meet criteria for dementia, delirium, or other major organic mental
disorders; American Psychiatric Association 2000).
The syndrome of mild cognitive impairment can have several different
underlying causes. In amnestic mild cognitive impairment, neurodegenera-
tion of an Alzheimer’s type is believed to be the most common etiology (Pe-
tersen and Morris 2005). However, depression or other psychiatric disorders,
metabolic or medical disorders, trauma, substance abuse or medication reac-
tions, and other conditions also may cause mild cognitive impairment of the
various types. In evaluating an individual who presents with mild cognitive
impairment, it may be helpful to review the full range of potential causes and
contributing factors that have been established for dementia (see Chapter 5,
“Dementia and Alzheimer’s Disease”).
As shown in Table 2–3, a substantial proportion of persons with amnestic
mild cognitive impairment eventually develop dementia, and a high pro-
Normal Aging 37
Table 2–3. Clinical presentations of memory loss in old age

Age-associated memory Mild cognitive impairment—
Feature impairment (AAMI) memory type (amnestic MCI)
Clinical Memory complaint Memory complaint or memory

presentation Normal mental status problems noted by an
Normal activities of daily informant
living Normal mental status
Normal activities of daily living
or very subtle changes
Memory test ≥1 SD below the average ≥1.5 SDs below the average
results level for young adults on a level for age peers on a
standardized memory test standardized memory test
Clinical course Generally stable for periods Progresses to dementia at the
of at least 4 years rate of 10%–12% per year,
but some remain free of
dementia for at least 10 years
Note. SD= standard deviation. For further information on AAMI, see Larrabee and Crook
1994. For MCI diagnosis and course, see Petersen and Morris 2005 or Winblad et al. 2004.
portion have Alzheimer-type brain changes on autopsy (Morris et al. 2001).

Clinical course is not as well established for nonamnestic mild cognitive im-
pairments, and it is important to recognize that mild cognitive impairment in
any form is not invariably progressive. Some persons with mild cognitive
impairment have a stable mild level of cognitive difficulty over intervals of
several years; others (as many as 40% in some studies) revert to normal per-
formance. In general, individuals who seek help from a physician because of
memory concerns (i.e., clinic-based populations) are more likely to show a
progressive course than are patients with mild cognitive impairment identi-
fied through population-based surveys.
Early interventions (e.g., with medications to enhance cholinergic system
function) could potentially be of benefit in slowing clinical progression of mild
cognitive impairment, but the first large-scale clinical trial of this type yielded
disappointing results. Older adults with mild cognitive impairment who re-
ceived donepezil or vitamin E did not differ from control subjects in cognitive
course over a 3-year follow-up, although participants with an apolipoprotein ε4
allele did show some benefit from donepezil (Petersen et al. 2005). These par-
ticular interventions may not have been optimal for treating prodromal demen-
tia symptoms or preventing their progression. Also, effective prevention of

Alzheimer’s disease and other dementias may require intervention earlier in the
life course (i.e., before mild cognitive impairment becomes apparent).
A difficulty for clinicians is that it is not yet possible to separate the indi-
viduals with mild cognitive impairment who will progress to dementia within
a few years from those who will not. When a clinical diagnosis of mild cogni-
tive impairment is combined with other markers of Alzheimer’s disease (see
Chapter 5, “Dementia and Alzheimer’s Disease”), the likelihood of dementia
is increased. However, in most cases, this additional information is not avail-
able, and only follow-up will determine whether the patient has a progressive
course. In clinical situations, it is most useful to explain the category of mild
cognitive impairment to the patient, discuss the need to track performance
over time (as in other chronic medical conditions), and encourage active com-
pensation for functional effect in the form of simplification of schedules, in-
creased use of note taking and organization, and sharing of responsibility for
mentally demanding tasks with others.
Personality and Emotional Changes

Personality and emotions have not been studied as thoroughly as cognition in
old age. Moreover, it is unknown whether observations about personality made
within the confines of a particular generation and culture can be generalized to
other places and times. The trends summarized in this section are most appli-
cable to currently old persons in Western urban societies.
Coexisting Stability and Change

When older adults compare their current and past selves, they usually per-
ceive more growth than decline in personality; that is, desirable traits are per-
ceived as outweighing undesirable traits to an increasing degree through
middle age and early old age. Developmental optimism is a term that has been
coined to describe this subjective growth in personality (Krueger and Heck-
hausen 1993).
In contrast, descriptive research suggests that basic personality traits such as
introversion-extroversion, psychological tempo, assertiveness, and hostility are
stable throughout adult life (McCrae et al. 1999). These personality disposi-
Normal Aging 39
tions are formed early in life and remain fairly constant in their relative promi-
nence in an individual’s makeup, despite variations in life experiences over the
years (Roberts and DelVecchio 2000).
Influences on Adult Personality

Precise patterns of ebb and flow in personality probably vary with genera-
tions, because each cohort encounters a unique set of pressures and opportu-
nities at successive life phases. However, certain causal processes appear to be
consistently important. One influential developmental force is the “social
clock” (Neugarten 1970). Most societies have rather firm beliefs about age ap-
propriateness of various actions. Some of these beliefs are formalized through
minimum-age laws or standards (e.g., for marriage, voting, or retirement),
but most are informally imposed. The social clock sets the pace for psychoso-
cial development within a given generation and provides a standard that in-
dividuals may internalize as a normal, expectable life cycle.
A second important force is the individual’s desire for continuity in per-
sonal past and present. Continuity has been described as “a grand adaptive
strategy” promoted by individual preference and reinforced by social approval
(Atchley 1989). The search for continuity may be at the heart of reminis-
cence, which occurs at all ages, and of the process of life review that is so com-
mon among elderly adults.
A third but poorly understood set of influences is genetic factors. A study
of elderly twins and multigenerational families found a genetic contribution
to negative affect but not to positive affect. Positive affect showed some re-
semblance across family members, but the resemblance appeared to be attrib-
utable to shared environments rather than genetic similarity (Baker et al.
1992).
Individual and social influences may combine to produce ordered transi-
tions or stages in adult personality. Erikson’s (1950) widely cited theory de-
picts development as progressing through eight age-correlated phases. Each
stage is associated with primary developmental tasks, and accomplishment of
each task has a bearing on subsequent stages. In late adulthood, the primary
tasks concern integrity versus despair; that is, each person is faced with mak-
ing sense of his or her actions over a lifetime and with judging the purpose
and effect of these actions. Morale in old age may depend on success in re-
solving this issue, in addition to those of earlier life phases.
To the extent that ordered transitions exist, they may differ for women and
men. Among middle-class women in the United States, increasing assertiveness
and feelings of efficacy are evident, combined with declining dependency, as
they approach their 50s. Among men of similar socioeconomic background, an
increase in interpersonal orientation and nurturance in later years is seen.
Most contemporary developmental theorists do not propose stage theo-
ries but instead emphasize the creative effect on personality of assuming and
relinquishing adult roles—most importantly, parenting (Gutmann 1987)—
or the dynamic interplay of cognitive processing resources and particular so-
cial contexts in shaping expressed personality (Staudinger and Pasupathi
2000).
Personality and Perceptions of Health

Older adults’ perceptions of their health have been linked to a variety of ob-
jective health outcomes, including mortality. Depression affects subjective
health concerns, as do certain personality traits. Neuroticism is inversely as-
sociated with self-perceptions of good health, whereas extraversion is posi-
tively associated; in a recent study, these associations were stronger among
persons age 75 and older than among persons in their 60s and early 70s (Du-
berstein et al. 2003). This same study found that openness to experience cor-
related with higher functional status throughout the late-life age range.
Emotions, Coping, and Well-Being

Research suggests that old age is an emotionally rich and complex phase of
life, and the salience of emotion, relative to more neutral knowledge and
skills, increases in later years (Carstensen 1992). Mentally normal older peo-
ple have better control over emotions than do younger adults, they reason
more flexibly about emotion-laden dilemmas, and they remember emotion-
ally charged information better than neutral facts (Isaacowitz et al. 2000).
This richness of emotional processing in older persons runs counter to the
generally declining patterns seen in many cognitive and physical skills. In-
stead of necessarily being linked to aging, the priority given to emotion
among older people has been interpreted by some as a reaction to shortened
time left, or “endings.”
Some studies have noted that older people tend to cope with stressful
events in different ways than do younger adults; older people rely more often
Normal Aging 41
on emotion-focused forms of coping, as opposed to active, problem-solving

approaches. Emotion-focused coping is more passive than confrontational, is
more individual than interpersonal, and is oriented toward control of distress-
ing feelings rather than toward alteration of stressful situations. Examples of
emotion-focused coping include distancing from the problem, accepting re-
sponsibility, and reappraising the problem positively. However, other research
has pointed out that the problem situations that older people face are often
less changeable than those of younger adults, and when the type of problem
is equated across ages, differences in coping styles are reduced or eliminated
(Staudinger and Pasupathi 2000).
Locus of control is another dimension that affects response to stressful sit-
uations. For example, older people who believe that their health is controlled
by powerful others adjust better to acute-care hospitals and high-constraint
long-term care than do those who consider their physical well-being to be un-
der their own control. In the community, belief in an external locus of control
is associated with increased visits to physicians during times of very high
stress. However, regardless of preexisting control orientation, studies of long-
term care show that sense of well-being tends to increase when residents are
given greater opportunities to regulate their own environment.
Although old age presents many personal and social obstacles, poor mo-
rale has been found to be the exception rather than the rule among older
adults. Current cohorts of older adults are not more prone to depression or
anxiety disorders than are young or middle-aged persons, and they do not
show lowered self-esteem as a general rule. Not surprisingly, older adults with
the highest morale tend to have better education and socioeconomic status
when compared to those older adults who did not have such advantages. Spe-
cific stressful events have less of an effect on subjective well-being in old age
than does attainment of personal goals or the onset of physical disability.
Older adults maintain a sense of contentment in the face of functional de-
clines through a combination of mobilizing additional resources, “downsiz-
ing” performance standards, and reducing the value placed on particular skills
or attributes (Rothermund and Brandtstadter 2003). Throughout the adult
life span, individuals compare their own performances and experiences with
those of others and often come to positive conclusions. This self-enhancing
appraisal serves to sustain self-esteem through difficult transitions and is a
support for mental health (Kwan et al. 2003).
An influential model of adult development that has emerged in recent

years relates resilience in old age (i.e., maintaining adaptive behavior in the face
of stress and recovering from adversity) to a process of selective optimization,
in which goals are reshaped to fit current limitations and environments, and
resources are spared for personally important activities that sustain self-esteem
(Baltes 1997). Elderly persons with the strongest sense of personal efficacy are
flexible in prioritizing goals and accommodating to role changes and resource
limitations. Those with several self-domains in which they hold themselves in
high esteem seem best able to cope with transitions imposed by role losses or
poor health (Staudinger and Pasupathi 2000).
Clinical Implications of Personality and

Emotional Changes
Core features of personality remain stable throughout adulthood, and any

marked change in mood or social behavior may indicate a disorder. However,
more subtle reordering of personal priorities and shifts in coping styles are
common with normal aging. It is particularly important not to measure older
people’s coping by youthful standards. Emotion-focused coping may be a sign
of personality development rather than regression, particularly if the problem
being faced (e.g., bereavement or serious illness) is difficult to resolve through
action.
In acute-care situations, the clinician must accurately appraise an individ-
ual’s beliefs about locus of control. Those individuals with an internal locus
of control adjust best if given an opportunity to participate in medical deci-
sion making, whereas those individuals with an external locus of control may
benefit more from knowing that they are attended by recognized experts.
Those individuals who suspect that their fate depends on chance may adjust
best if the care environment is consistent and predictable. Other aspects of
personality need to be considered as well. The increased vulnerabilities that
accompany old age may amplify neurotic traits, increasing susceptible indi-
viduals’ worries about health and making it more difficult to provide reassur-
ance based on objective results. By contrast, socially extroverted persons may
respond well to encouragement to share their experiences with others (e.g., by
participating in health-oriented support groups).
Normal Aging 43
Increasing salience of emotional matters can influence assessment, espe-

cially of cognitive skills. Older patients may not see the relevance of being
asked to learn a list of words or may editorialize about emotional themes in
stories they have been asked to remember. Varying the instructions of the task
(e.g., encouraging the person to try to remember the story as if he or she were
going to relate it to a friend or grandchild) can sometimes help to direct at-
tention and effort toward the task requirements to permit a valid assessment.
Older people can benefit from the full range of psychotherapies used
with younger people (see Chapter 4, “Mood Disorders—Treatment”). Some
highly educated and thoughtful elderly people are well suited for long-term
therapy addressing intrapsychic tasks of later life. For many others, situational
interventions, aimed at modifying real-life problems, may be most appropri-
ate, and in general, there has been a trend toward short-term, problem-
focused therapies in recent years. In either case, goal setting for the future
should be part of the psychotherapy agenda.
Social Context of Aging

Old age is accompanied by role change and, often, role loss. Most people can
expect transformations in occupational, family, and community roles, and for
many, the number of different roles declines in later life.
Education, Work, and Financial Status

The average education level of older Americans has increased in recent de-
cades; in 2003, nearly three-fourths of persons age 65 and older had a high
school diploma. Older Asian Americans had the highest percentage of persons
(29%) with at least a bachelor’s degree. By contrast, older black and Hispanic
Americans remained disadvantaged in terms of education (Figure 2–1).
In industrialized countries, participation of older men in the labor force has
declined in recent decades. In the United States between 1963 and 2003, the per-
centage of men ages 62–64 years in the workforce declined from 76% to 50%,
and among those 70 and older, from 21% to 12% (Federal Interagency Forum
on Aging-Related Statistics 2004). Most of the decline took place before the
1980s, as the youngest age for Social Security eligibility dropped to 62 and older
people began to enjoy better incomes. The leveling off of work rates in recent de-
cades has been attributed to elimination of mandatory retirement laws and
100 High school graduate or higher

Bachelor’s degree or higher
80
60
40
20
0
Total Non-Hispanic Black alone Asian alone Hispanic
white alone of any race
Figure 2–1. Educational attainment of Americans age 65 and older,

2003.
tics 2004.
changes in Social Security policies regarding delayed retirement credits and earned
income. Good health, a strong psychological commitment to work, and an active
distaste for retirement are among the strongest predictors of continuing to work
past traditional retirement ages. Employment trends for women have moved in
the opposite direction. Labor force participation rates have increased for older
women since the early 1960s, as new cohorts with a history of working outside
the home have begun to age. In 2003, 64% of women ages 55–61 years, and 23%
of those ages 65–69, were employed.
Although people who retire report that they miss the money and opportu-
nities for social contact provided by their everyday work, most take retirement
in stride, adopting new routines and activities to take the place of their work.
This type of adjustment is particularly likely when retirement is predictable or
self-imposed and when postretirement income is adequate. Health problems,
Normal Aging 45
either physical or mental, usually do not increase in the weeks or months after
retirement, and some studies show that retirees have lower stress levels and en-
gage in more healthful behaviors than do similar-age peers who are still em-
ployed (Midanik et al. 1995).
Because of Social Security and other pension programs, a majority of
older people in the United States are financially independent. Persons with
medium income now constitute the largest group of older Americans (35%),
and 26% have been rated as having high income (Federal Interagency Forum
on Aging-Related Statistics 2004). In 2003, Social Security provided 39% of
the total income for Americans age 65 and older, with an additional 25% pro-
vided by personal earnings, 19% by pensions, and 14% by asset income. The
poorest older adults are heavily dependent on Social Security. In 2003, for ex-
ample, Social Security provided more than 80% of the funds of older Amer-
icans in the lowest two-fifths of the income distribution.
About 10% of Americans age 65 and older were considered poor by federal
guidelines in 2002, compared with 35% in 1959 (Federal Interagency Forum
on Aging-Related Statistics 2004). However, elderly women and members of
minority groups have more severe financial strain than do older white men. In
2002, 12% of older women lived in poverty, compared with 8% of older men.
Twenty-four percent of older black Americans and 21% of older Hispanics had
incomes below the poverty line, compared with 8% of older non-Hispanic
white Americans.
Marriage and Widowhood

The availability of marital relationships in old age differs sharply for women
and men. In 2003, 71% of men and 41% of women age 65 and older were
married; among those age 85 and older, 59% of men, but only 14% of
women, were married (Federal Interagency Forum on Aging-Related Statis-
tics 2004). For those with long-term marriages that continue into old age, sat-
isfaction may increase in later life compared with earlier marital phases, and
there may be greater agreement between the partners on important topics
such as money management and relationships with children.
Many older women live alone in their final years because their husbands
have died or because separations are imposed by a spouse’s failing health
(Figure 2–2). Because of increased life expectancy, rates of widowhood are
gradually declining, but this trend is being offset by increasing numbers of di-
vorced and single older persons. Rates of widowhood are similar for Hispanic
and non-Hispanic white women but are higher for black women.
With other relatives Alone

With spouse With nonrelatives
M W M W M W M W M W
100
80
60
40
20
0
Total Non-Hispanic Black alone Asian alone Hispanic
white alone of any race
Figure 2–2. Living arrangements (percentage of population) for men (M)

and women (W) age 65 and older, 2003.
tics 2004.
Older adults respond to bereavement in many different ways. According

to a recent prospective study, approximately one-half of new widows or wid-
owers cope with the loss of their spouse with relatively low levels of distress,
and what was once considered a typical response to bereavement (i.e., a
marked increase in distress following the loss, with abatement over time) is
much less common (Bonanno et al. 2004). Normal bereavement generally
Normal Aging 47
does not produce a loss of self-esteem or inappropriate guilt (see Chapter 3,

“Mood Disorders—Diagnosis”), and chronic grief, persisting beyond 1–2
years, is relatively rare. However, men and women with few friends tend to
have a harder time adjusting to widowhood.
Extended Families, Friends, and Group Involvement

Compared with younger people, elderly individuals tend to have smaller social
networks and less frequent interpersonal contacts. However, most older per-
sons are socially active within this smaller arena. Older people rely more
heavily than younger adults on family members and long-term friendships for
input on important matters. Nearly 80% of older adults have at least one living
child, and at least two-thirds report that they have seen their children within
the past week (U.S. Senate Special Committee on Aging 1987–1988). Elderly
people are also actively involved with their siblings. As individuals realize that
they are aging, sibling relationships appear to increase in importance, with sis-
ters playing a particularly active role in maintaining kinship networks.
Intimate, confiding relationships may be most valuable to a person’s well-
being and mental health in old age. About four of five elderly persons report
having confidants. When available, spouses are most likely to be listed as con-
fidants, followed by friends, children, and siblings. However, among cur-
rently old Americans, women are less likely than men to view their spouse as
the main source of social support (Gurung et al. 2003). Among persons age
85 years and older, declining functional ability is the biggest obstacle to con-
tinuing old friendships or making new friends. Nonetheless, in one study,
more than 50% of the persons at this age reported one or more close friends,
and 75% had weekly contact with persons they identified as friends (Johnson
and Troll 1994). A recent population-based study in Chicago, Illinois, found
smaller social networks and lower levels of social engagement among elderly
black persons compared with elderly white persons (Barnes et al. 2004).
Being socially involved and depended on by others is important for suc-
cessful aging. Fulfilling multiple social roles (e.g., worker, spouse, caregiver,
and grandparent) has been linked to higher life satisfaction and feelings of
self-efficacy for both white and black older Americans. Having a sense of so-
cial worth is also important for health and survival. Two recent studies, one
in Japan and one in the United States, found reduced rates of death among
older adults who perceived themselves as useful to others or were involved in

giving social support (Brown et al. 2005; Okamato and Tanaka 2004).
Increasing numbers of grandparents are now providing custodial care for
grandchildren or extensive noncustodial caregiving, especially in black and
Hispanic families. About one-half of older Americans attend church regularly,
and about one in six are active in volunteering. Religious beliefs may play an
especially important role in adaptation for older Americans of African de-
scent, whereas elderly white persons may rely more often on nonreligious so-
cial connectedness (Consedine et al. 2004).
Clinical Implications of Social Context

Psychiatrists must identify sources of social support for older people, facilitate
meaningful contacts for those without social networks, and promote reciprocity
in assistance when possible. Intergenerational family therapy can be useful, par-
ticularly if it reinforces older patients’ ability to give as well as to receive.
Because older women are frequently widowed and may outlive other kin,
they are especially likely to find themselves alone in advanced old age.
Women may be more adept than men at forming friendships in later life, but
this possible strength may be counteracted by physical or sensory disability.
For those with very restricted social resources, therapists must sometimes be
willing to provide periodic support on a long-term basis.
Being needed by others and making contributions to one’s family or soci-
ety as a whole are important for maintaining a sense of self-worth. Helping
older patients to identify meaningful ways to stay involved, despite changes
in physical or mental abilities, can be as important as providing opportunities
to mourn the loss of past abilities or social roles.
Biological Aging
What Is Aging?
A useful definition of aging was proposed by Birren and Zarit (1985): “Bio-
logical aging, senescing, is the process of change in the organism, which over
time lowers the probability of survival and reduces the physiological capacity
for self-regulation, repair and adaptation to environmental demands” (p. 9).
Modern gerontologists distinguish primary aging, which is postulated to re-
Normal Aging 49
flect an intrinsic, presumably genetically preprogrammed limit on cellular

longevity, from secondary aging, which is due to the accumulated effects of en-
vironmental insult, disease, and trauma.
Primary aging seems to account for the relatively constant maximum life
span observed in almost all animal species studies, whereas secondary aging
explains much of the variability among individual members of a species. That
primary aging is “built into” the cell was first appreciated by Hayflick and as-
sociates (Hayflick 1965; Hayflick and Moorhead 1961) in a series of experi-
ments that established the maximum number of cell divisions (doublings)
that would occur in carefully cultured normal human cells at about 50±10.
As cultured cells approach this limit, many functional capacities are lost, with
the final cessation of cellular reproduction apparently reflecting accumulated
functional losses. Evidence that the “Hayflick phenomenon” is under genetic
control includes 1) a fair correlation between the doubling limit and the max-
imum species-specific life span of the cell donor and 2) a reduced doubling
limit in cells cultured from patients with genetic diseases of accelerated aging,
such as progeria (Hutchinson-Gilford syndrome) and Werner’s syndrome.
The observation that cells in culture retain their preprogrammed doubling
limit even after being frozen for years suggests that the doubling limit is not
related only to total time elapsed. The observed inverse relation between dou-
bling capacity and the age of the cell donor indicates that the limit is not just
an in vitro phenomenon; that is, doublings in vivo appear to “count” as well
as those that occur in vitro. Similar losses of functional capacity (i.e., cellular
aging) have since been observed in all cell types, including those with little or
no reproductive capacity, such as neurons.
The precise mechanism underlying the observed limits on normal cellular
division is not completely known, but several lines of evidence point to telomeric
shortening as at least one likely “clock” mechanism. Telomeres are unique pro-
tein-DNA structures that make up the terminal region of chromosomes in eu-
karyotic cells. The telomere section of the chromosome does not contain
genetic information; rather, it is composed of repeated stretches of six nucle-
otides (TTAGGG in vertebrates) that seem to perform a stabilizing or protec-
tive function for the end of the chromosome (Hodes 1999). Multiple studies
have shown that telomeres shorten with each cell division, and when a certain
limit is reached, cellular division no longer occurs and cellular “senescence” has
been reached. Evidence that the observed telomeric shortening is a key determi-
nant of cellular senescence includes 1) the observation that telomerase, a ribo-

nucleoprotein enzyme that mediates RNA-dependent synthesis of telomeric
repeats and prevents telomeric shortening, is found in high concentration in
germ cells and malignant cells, both of which are “immortal” and do not se-
nesce; and 2) the observation that when the expression of telomerase is induced
in normal cells, senescence is delayed significantly. However, telomeric shorten-
ing has not been observed in all senescent cell cultures, and “environmental”
factors such as oxidative stress, DNA demethylation, and accumulation of
DNA cross-links, which can induce “premature senescence” (i.e., failure of cells
to divide before the Hayflick limit has been reached), also have been proposed
to play a role in normal cellular senescence. Reddel (1998), summarizing this
literature, proposed two models of senescence induction that take these and
other potential inducers of premature senescence into account. In his models,
environmental and intracellular factors operate either on a single clock mecha-
nism, such as telomeric shortening, or on multiple clock mechanisms. In the
latter model, senescence is determined by whichever clock mechanism reaches
its critical threshold first. Regardless of which model turns out to be best sup-
ported by the evidence, it is not at all clear that the failure of cells to continue
reproducing can account for all aging changes in the organism per se.
Primary Aging: Structural and Functional Changes

The major structural changes in humans that have been attributed to primary
aging are listed, by organ system, in Table 2–4, along with the major func-
tional consequences of these changes. Note that cross-sectional studies pro-
duced most of the tabulated findings. In addition to the general shortcomings
of such studies described earlier, data on the anatomical and physiological ef-
fects of age are usually confounded by selection biases (i.e., random samples
are rarely used in this type of research) and by the uncontrollable effects of
secondary aging.
Aging and the Clinical Process

Although psychiatry textbooks and manuals (including this one) are tradi-
tionally divided into chapters and sections that cover specific diagnostic en-
tities, a large proportion of elderly patients who present with cognitive,
emotional, and behavioral signs and symptoms do not fit cleanly into well-
Normal Aging 51
defined (DSM-IV-TR) diagnostic categories, and the older the patient, the
more this tends to be the case. The ability to initiate treatment on the basis
of only provisional diagnostic impressions, to continue to gather information
and modify the treatment plan as a clearer picture emerges, and to take age-
related changes in clinical circumstances into account throughout the process
is the hallmark of the well-adapted and successful geriatrician.
The following case report is typical:
Mr. A, an 85-year-old married, retired businessman presenting for an outpa-
tient assessment, tells the clinician, “There’s nothing wrong with me, and
I don’t need to be here.” Gentle probing induces Mr. A to admit to mild
memory impairment, some loss of appetite and energy, and multiple somatic
symptoms, including dry mouth, intermittent urinary retention, chronic
pain in several body parts, occasional episodes of dizziness, and occasional
constipation. Mr. A’s spouse adds that she has noticed his irritability, chronic
worrying, and social withdrawal and an increasing tendency to stay in bed.
She goes on to say that he had been working part-time at a company that he
started 40 years ago, which is now being run by their son, but was “invited”
to stop coming to the office about 6 months ago and has not been back since.
Late in the session, she mentions that Mr. A’s brother died a month prior to
the clinic visit. Mr. A discounts the importance of both of these events.
Mental status examination finds mildly depressed mood, anxiety, short-
term memory impairment that is partially ameliorated by cues, and inconsis-
tent results on assessment of frontal executive functions. Mr. A has chronic
moderate hypertension and coronary artery and peptic ulcer disease; he takes
daily doses of a statin, two antihypertensive medications (including a β-
blocker), a proton pump inhibitor, and intermittent hydrocodone bitartrate–
acetaminophen preparations, in addition to stool softeners, ginkgo biloba,
low-dose aspirin, and vitamin E.
By the end of the interaction, it is clear that Mr. A is suffering and that
his physical and social functioning have declined, but the clinician’s persistent
effort has failed to establish a clear timetable of the onset and progression of
any of the symptoms or their temporal relation to losses, other social stressors,
or his other illnesses and their treatments. The patient has no history of men-
tal or emotional problems and does not qualify for any DSM-IV-TR diagno-
sis (outside the not-otherwise-specified categories), and he says, “Doc, if you
had my medical problems, if you’d been through what I’ve been through, you
wouldn’t be so chipper, either. I don’t need a psychiatrist, and I don’t need
treatment for any ‘mental illness.’”
With this “typical” patient in mind, then, a few general principles of di-
agnosis and treatment are important to keep in mind.
Table 2–4. Primary aging: changes in anatomy and function of major organ systems

System Anatomical changes with age Functional changes with age
Cardiovascular
Heart Decreased size, flexibility of collagen matrix; Impaired left ventricular diastolic filling, reduced
lipofuscin and fat deposition in β-adrenergic (i.e., chronotropic and inotropic)
myocardium; fatty infiltration and response to catecholamines, leading to decreased peak
calcification of aortic and mitral valves exercise cardiac index and ejection fraction (Schulman
1999)
Arteries Redistribution and molecular rearrangement Increased systolic blood pressure
(cross-linking) of elastin and collagen in
arterial walls; calcification
Respiratory
Lungs Enlarged alveolar ducts and alveoli; loss of Reduced ventilatory capacity, especially during exercise
elasticity
Musculoskeletal Increased chest wall and joint rigidity; Same as above
increased kyphosis; degeneration and
calcification of cartilage
Gastrointestinal Some loss of smooth muscle cells of intestine; Reduced eliminatory efficiency: constipation; reduced
atrophy of gastric mucosa; increase in metabolism of drugs
gastric pH; some loss of hepatocytes;
reduction in hepatic blood flow
Table 2–4. Primary aging: changes in anatomy and function of major organ systems (continued)
Genitourinary Loss of renal mass, loss of glomeruli, Reduced glomerular filtration rate and renal plasma
thickening of basement membrane of flow; loss of bladder-emptying capacity
glomeruli and tubules, development of
tubular diverticula, intimal thickening of
arteries, development of afferent-efferent
shunts in juxtamedullary glomeruli,
obliteration of arterioles in cortical
glomeruli (Davison 1998); reduced bladder
elasticity, especially in women; prostate
enlargement in men
Endocrinological Atrophy and fibrosis; loss of vascularity; General decline in secretory rate, but resting hormone
changes may be very minimal blood levels may remain constant as clearance also
declines
Nervous Loss of brain weight and volume in most Inconsistent evidence of reduced blood flow; reduced
studies; loss of neurons, depending on metabolism of glucose and oxygen; intellectual
brain area studied; loss of dendritic arbor, changes as described in text (see “Cognitive Abilities
with reduced interneuronal connectivity; in Later Life: A Processing Resource Model”)
Normal Aging
interneuronal accumulation of lipofuscin
and loss of organelles; neurofibrillary
degeneration of neurons; accumulation
of senile plaques, especially in
hippocampus, amygdala, and frontal cortex
53
Table 2–4. Primary aging: changes in anatomy and function of major organ systems (continued)

Musculoskeletal Reduced muscle and bone mass; Loss of muscular strength and stamina
demineralization of bone; increased fat
in muscles and calcium in cartilage;
degeneration of cartilage; loss of elasticity
in joints
Immunological Involution of thymus; reduced proportion Increased susceptibility to cancer
of naïve T cells; increased proportion of
activated/memory T cells; decreased
expression of interleukin-2 receptors;
decreased cellular proliferative response to
T-cell receptor stimulation (Ginaldi et al.
1999)
Special senses Yellowing of lens in eye Loss of auditory and visual acuity, especially night
vision
Normal Aging 55
Diagnostic Process
• Identify “secondary syndromes” first. A growing list of general medical con-
ditions and medications appear to be risk factors for clinically significant
depression, and in some cases, appropriate treatment of the general med-
ical condition and/or modification of the medication regimen may be suf-
ficient to ameliorate depressive symptoms.
• Do not accept bland denial of symptoms. Sometimes the clinician must use
several different approaches, with terms that the patient can understand
and is comfortable with, before the true picture emerges. Some elderly pa-
tients who vehemently deny being depressed will admit to “the dwindles”
or will acknowledge loss of interest in usual activities or irritability.
• Seek information from ancillary sources when possible. Ancillary sources in-
clude the spouse, caregiver, board and care home or nursing home spon-
sor or head nurse, and other physicians. Lack of insight exacerbated by a
widespread cultural bias against acknowledging emotional or mental in-
firmity may render the patient the least reliable informant.
• Maintain a healthy index of skepticism. If the history does not fit the cur-
rent clinical picture, the clinician should probe more deeply. Some bipolar
patients and their family members “forget” hypomanic episodes, only to
“remember” when the patient switches into one: “Oh yes, he was just like
this back in 1984!” “Abrupt onset” of significant cognitive impairment
sometimes turns out to be merely “abrupt discovery” of a long-developing
condition that has been acutely exacerbated by the patient’s anxious re-
sponse to a relatively minor change in living circumstances.
Therapeutic Process
• First, undo harm. Some presenting signs and symptoms may be due to side
effects and adverse reactions to over-the-counter and prescription medi-
cations used for physical conditions. Replacement with an alternative
agent, or dosage adjustment of medications that can provoke, mimic, or
exacerbate depressive or anxiety symptoms, may render specific psycho-
pharmacological treatment unnecessary. See Table 2–5 for a list of com-
mon offenders.
• Do not hesitate to treat just because a full syndrome is not present. There is
growing recognition of the clinical significance of subsyndromal condi-
Table 2–5. Medication-induced signs and symptoms of mental

disorder
Medication Signs and symptoms
Antihistamines Sedation, memory impairment

β-Blockers Sedation, psychomotor retardation, reduced energy
Antiparkinsonian Hallucinations, agitation
agents
Narcotic analgesics Sedation, impaired attention and concentration
Steroids Anxiety, emotional lability
Decongestants, Sleep disturbance, anxiety
bronchodilators
tions in elderly patients, as shown by the emergence of new diagnostic cat-

egories such as minor depressive disorder, mild neurocognitive disorder
(see Appendix B, “Criteria Sets and Axes Provided for Further Study,” in
DSM-IV-TR), and age-associated memory impairment (listed in DSM-
IV-TR as “780.9 Age-Related Cognitive Decline” in the “Other Condi-
tions That May Be a Focus of Clinical Attention” chapter).
• Modify psychotherapeutic technique as necessary. Sensory losses may require
that the therapist sit closer and speak more loudly and slowly than would
be appropriate for middle-aged patients. Amplification devices may be of
value; generally, desktop systems offer much greater clarity and resolution
than standard hearing aids. Impaired short-term memory may require
that the therapist reiterate key points several times and may contribute to
learning difficulties that are indistinguishable from resistance and denial.
For example, older patients may be more prone to forget appointments
and may need reminder calls. Sensory losses and reduced short-term
memory also may contribute to a generalized reduction in attention span
and decreased capacity for therapeutic work, so sessions may need to be
shorter than with younger patients. Musculoskeletal aging may impair
mobility and interfere with older patients’ ability to come to appoint-
ments, and the role of telephone contact in their care may be expanded.
• Determine the patient’s baseline physiological and pharmacological status
before initiating pharmacotherapy. Usually, the psychiatrist must evaluate
hepatic and renal function and the function of any organ or organ system
Normal Aging 57
that may be adversely affected by medications (e.g., an electrocardiogram

should be obtained before initiating therapy with tricyclic antidepres-
sants). A careful review of the list of other medications the patient is tak-
ing, or likely to begin taking, is also important because psychotropic
medications affect the function of several hepatic microsomal cytochrome
P450 enzymes. This effect can cause significant changes in the blood lev-
els of nonpsychotropic and psychotropic medications.
• Respect age-related pharmacokinetic and pharmacodynamic changes. Of the
four major determinants of pharmacokinetics—absorption, distribution,
metabolism, and excretion—all but absorption are significantly affected
by normal aging changes (Desai 2003). The distribution of drugs in the
body is reliably altered by the aging process, primarily as a result of relative
loss of body water and lean body mass. Both of these changes result in rel-
atively increased plasma concentrations of drugs that are distributed in
body water, such as lithium carbonate, or in lean body mass, such as
digoxin (Cusack et al. 1979). Conversely, drugs that deposit in lean body
mass and adipose tissue, such as diazepam, are distributed in a larger “ap-
parent volume” (Greenblatt et al. 1980) and will attain somewhat lower
plasma concentrations than in a younger patient. Aging is also associated
with reduced amounts (in the range of a 20% reduction) of serum albu-
min, the serum protein most highly “bound” to drugs in plasma. For
drugs that are highly albumin bound (i.e., more than 95%), such as furo-
semide or warfarin, the reduction may free a significantly higher propor-
tion of drug for distribution to its site of action, with resultant greater
drug effect.
After distribution, most drugs undergo two-phase metabolism in the
liver. The first phase is oxidation, reduction, or hydrolysis, reactions cat-
alyzed by enzymes in the microsomal fraction of homogenated liver tis-
sue. The second phase of metabolism is acetylation, or conjugation with
glucuronide, sulfate, or glycine; second-phase metabolism usually pro-
duces active or inactive water-soluble compounds that are then excreted
by the kidney. Although reductions in hepatic blood flow (about 45% be-
tween ages 25 and 65), in relative hepatic mass (about one-third), and in
hepatic enzyme activity have been seen in elderly individuals, examina-
tion of the actual rate of metabolism of drugs in elderly subjects has pro-
duced contradictory results, and few generalizations are possible. One
such generalization is that hepatic conjugation of drugs is relatively spared

by age effects; the significance of this sparing with respect to benzodiaz-
epine therapy is shown clearly in Table 7–8 in Chapter 7 (“Anxiety Dis-
orders and Late-Onset Psychosis”).
Age effects on renal excretion of drugs have been much more clearly delin-
eated. Reduction in glomerular filtration rate (which generally corresponds to
rate of excretion of drugs) of approximately 1% per year between ages 30 and
80 has been documented, as has comparable reduction in renal plasma flow and
renal tubular function, including absorption and secretion (Rowe et al. 1976).
For drugs that are excreted by the kidney unchanged, such as lithium salts, or
that have active water-soluble metabolites, such as desipramine (i.e., 2-OH-
desipramine), this reduction may have great clinical significance. For other
agents with inactive water-soluble metabolites, this change is less important.
When pharmacokinetic factors are constant, increased or decreased effec-
tiveness of drugs can be assumed to reflect pharmacodynamic changes (the ac-
tual physiological response produced by a drug at its site of action). Only a few
such pharmacodynamic changes have been documented in healthy elderly per-
sons: increased sensitivity to the depressant effects of benzodiazepine anxiolyt-
ics and hypnotics on the central nervous system (Greenblatt et al. 1977),
increased sensitivity to the effects of warfarin, and decreased sensitivity to the
chronotropic effects of isoproterenol. The emerging field of pharmacogenetics,
which attempts to understand and predict genetically determined interindi-
vidual differences in pharmacokinetic and pharmacodynamic responses to
drugs, is likely to produce clinically applicable findings in the near future
(Malhotra et al. 2004). The age-related changes in pharmacokinetics and phar-
macodynamics cited above are reflected in the following bullet points:
• Respect the treatment setting. Psychopharmacotherapy in the inpatient set-

ting should be conducted much more aggressively than in the outpatient
setting. Almost every psychopharmacological agent on the market is most
effective at the highest dosage the patient can tolerate, so an approach that
reaches that dosage as rapidly as is safe is most appropriate in the inpatient
setting, where side effects and adverse reactions can be monitored and
managed. In the outpatient setting, the principle of start low, go slow
is more appropriate. The clinician should begin with relatively small
Normal Aging 59
doses—for example, one-third to one-half of the usual adult dose. The cli-
nician should proceed slowly when dosage increase is indicated and re-
main alert for the development of adverse reactions, side effects, and drug
interactions.
• Choose appropriate target symptoms. Failure to identify appropriate target
symptoms is a common cause of unsuccessful treatment. Target symp-
toms may be absolutely inappropriate (e.g., social withdrawal in a de-
pressed patient who is characterologically antisocial, or unhappiness and
dissatisfaction in a patient who feels stuck in a bad marriage) or tempo-
rally inappropriate (e.g., adjusting antipsychotic therapy to eliminate
delusional content while failing to appreciate improved behavior and re-
duced agitation; the latter are appropriate early indicators of adequate
treatment, whereas the former may require months of therapy). Similarly,
typical early indicators of response to antidepressants are improvement in
sleep, appetite, and anxiety; subjective improvement in mood usually ap-
pears later in the course of therapy. In general, global improvement is a
suboptimal target of therapy because it is relatively more sensitive to the
vicissitudes of daily life, is subject to more interrater variability, and is
more influenced by the mood and expectations of a single rater than are
more concrete targets such as appetite, sleep, and specific psychological
states such as hopelessness, helplessness, and anhedonia.
• Keep it simple. The apparently widespread practice of “mixing and match-
ing” antidepressants, antipsychotics, and anticonvulsants to achieve just
the “right balance” of neurotransmitter activation and inhibition is inad-
visable on several counts. First, because these combinations have had es-
sentially no systematic study, every instance of their use is an “n of 1”
clinical trial in which the patient is an unwitting subject; and second, such
polypharmacy renders the clinical picture unnecessarily complex, making
the task of sorting out which symptoms are “primary” and which are side
effects or adverse reactions a matter of guesswork.
• When possible, change one thing at a time. One goal of psychopharmaco-
therapy is to identify ineffective approaches. Only if treatment is con-
ducted systematically, adequate dosages are prescribed, adequate amounts
of time are allowed, and changes are made one at a time is it possible to
determine which treatments are ineffective or unnecessary and need no
further exploration. For example, in a patient whose symptoms are unre-
sponsive to a tricyclic antidepressant, the dose is increased and lithium is

added; rapid response follows. Which maneuver is responsible? Is the lith-
ium necessary? Would a higher dose alone have sufficed?
• Do not use medications only for their side effects. Common violations of this
principle include prescribing increasing amounts of neuroleptic medica-
tions when sedation is desired, prescribing antihistamines for their hyp-
notic or anticholinergic side effects, or prescribing antidepressants as
hypnotics for nondepressed patients. (A possible exception is the use of
trazodone in subantidepressant dosages as a hypnotic. Trazodone is diffi-
cult to use as an antidepressant in the elderly because of its sedative effects
and its tendency to provoke orthostatic hypotension in antidepressant
dosages, but in low [i.e., 50–100 mg] dosages, it is safe and effective as a
hypnotic.) Failure to follow this principle with elderly patients increases
the risk of adverse reactions caused by overtreatment (e.g., neuroleptic
malignant syndrome or anticholinergic delirium). This principle does not
discourage selection of an agent when its therapeutic effects and its side
effects are both desirable, such as the use of a sedating antidepressant for
a depressed patient with sleep disturbance.
• Beware of undertreatment. The geriatric literature appropriately empha-
sizes the side effects and adverse reactions that all psychotropic medica-
tions can cause. However, most elderly patients are quite sensitive to
medication side effects, so a clear signal usually alerts the clinician when
the dosage is reaching its ceiling. Such is not the case with undertreat-
ment, when partial response can “freeze” therapeutic response at a subop-
timal level. Diagnostic uncertainty or therapeutic timidity on the part of
the clinician may lead to these outcomes. A good rule of thumb is to in-
crease dosages until clinical response is clear; if response diminishes or pla-
teaus before complete remission, dosages should be increased again, with
the ceiling defined as the development of minor side effects that do not
remit over several days. At this point, minor dosage reduction may be ap-
propriate. In this way, the clinician can be reasonably confident that the
most effective (i.e., the highest) dosage possible for that patient has been
reached. Of course, with agents for which a true therapeutic window ex-
ists (possibly including nortriptyline), this approach requires particularly
close monitoring of clinical response and determination of serum drug
levels when available.
Normal Aging 61
• Beware of inducing withdrawal or overdose. When a patient is hospitalized

and his or her “regular dosage” of medication is continued in the hospital,
problems may occur. Unreported undermedication or overmedication be-
fore admission can render the prescribed dosage much too low or too
high.
• Maintain an optimistic and supportive attitude. This stance is particularly
important during the first few days and weeks of therapy, when the ratio
of side effects to clinical gain is particularly high. Optimism does not en-
tail or justify unrealistic expectations but helps to maximize the placebo
effect, which has been shown to account for about one-half of the efficacy
of psychopharmacological agents.
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3
Mood Disorders—Diagnosis
Depression is the most common mood disorder in later life. It can have
serious consequences, including “disability, functional decline, diminished
quality of life, mortality from comorbid medical conditions or suicide, de-
mands on caregivers, and increased service utilization” (Charney et al. 2003,
p. 664). Because of the seriousness of these consequences, geriatric depression
has been identified as a major public health problem, yet it is undiagnosed in
about 50% of cases (Mulsant and Ganguli 1999). Even when it is recognized,
depression in the elderly tends to be undertreated: Steffens and colleagues
(2000) found that only 35.7% of elderly patients with major depression were
taking an antidepressant; of these, it is likely that a substantial minority were
less than optimally compliant with treatment (Katon et al. 1999). Several
factors contribute to this suboptimal response by the medical profession,
including 1) the “normative fallacy”—that is, the belief that symptoms of
depression are “normal” or “expectable” given the patient’s age, social circum-
stances (including recent losses), and medical condition; 2) the tendency of
clinicians to attribute neurovegetative symptoms and signs (such as loss of
energy, poor appetite, and disturbed sleep) to concomitant medical problems;
3) the reluctance of many older patients to acknowledge “mental” problems,
67
which, especially when exacerbated by memory impairment, may force the

clinician into an uncomfortable reliance on third parties for historical infor-
mation; and 4) the complementary tendency of many older patients to express
psychic distress in physical terms (Gallo and Rabins 1999), leading to unnec-
essary, expensive, and sometimes risky diagnostic searches for nonexistent
physical conditions.
Clinically significant depression takes many forms in the elderly, and the
well-defined diagnostic categories recognized in DSM-IV-TR (American Psy-
chiatric Association 2000) may not cover every clinical presentation. Depressive
signs and symptoms are commonly seen in normal and complicated grief, are
associated with several medical illnesses and medications, present as well-
defined “primary” syndromes (including major depression and dysthymia), and
occur as features of diagnostic entities that remain under study, such as minor
depressive disorder and depressive personality disorder, both listed in Appendix
B (“Criteria Sets and Axes Provided for Further Study”) of DSM-IV-TR.
The first part of this chapter is organized accordingly. It assumes that the
clinician has identified clinically significant symptoms and signs of depression
and is attempting to make a definitive diagnosis. The chapter sections com-
prise a differential diagnosis of depressive features, beginning with “normal”
grief and complicated grief, then addressing depression secondary to a general
medical condition, next focusing on substance-induced depression, then dis-
cussing the primary syndromes of major depression (including some com-
mon variations in clinical presentation) and dysthymia, and finally attending
to the proposed primary syndromes of minor depression and depressive per-
sonality disorder. Subsequent sections tackle laboratory and psychological
tests and depression rating scales useful in the diagnostic process, discuss sui-
cidality in the elderly, and provide a brief review of theories of the pathogen-
esis of depression.
“Normal” Grief (Bereavement)

Studies generally concur that uncomplicated grief or bereavement may include
any or all of the features of major depression except suicidality, psychosis, severe
loss of self-esteem and/or functionality, and psychomotor retardation. Appetite
and sleep disturbance, multiple somatic complaints, anhedonia, anxiety, mild
feelings of self-deprecation, the passive wish to “join the loved one,” sadness,
Mood Disorders—Diagnosis 69
and other dysphoric moods are common but generally less severe than in major
depression. Depressed patients are more prone to focus on themselves and their
role in the loss and, consequently, are more likely to feel guilt and reduced self-
esteem than are nondepressed mourners, who tend to think more of the lost ob-
ject (Gallagher et al. 1982). One series of studies found that 35% of a group of
109 bereaved widows (average age=61 years) were depressed 1 month after the
death of their spouse, but only 17% remained depressed after 13 months.
Moreover, the best predictor was depression itself: 75% of those depressed at 13
months were depressed at 1 month (Bornstein et al. 1973; Clayton et al. 1972).
In a sample of 133 widows and widowers (average age=70.6 years), only 10%
had symptoms that met DSM-III-R (American Psychiatric Association 1987)
criteria for major depression 13 months after the death of a spouse, but 14%
had symptoms that met criteria at 25 months. In this study, the authors also ob-
served “clinically significant” depressive symptoms in the 86% whose condi-
tions did not meet formal diagnostic criteria (Zisook et al. 1994). In another
series of studies, Glick et al. (1974) and Parkes (1965, 1972) discerned the fol-
lowing approximate stages of normal bereavement:
1. The first few weeks after the death of a loved one: During this initial period,
numbness, shock, disbelief, and emptiness are often accompanied by in-
tense anxiety, sleep disturbance, and somatic complaints.
2. The first year after the death of a loved one: This is a period of adjustment, dur-
ing which cognitive and affective “working through” occurs via a process of
recollection, fantasy, and rationalization. This phase is completed when ac-
ceptance occurs.
3. After the first year postloss: A recovery phase ensues, during which “redef-
inition” of self without the lost loved one occurs.
Although the studies cited earlier did not address the specific circum-
stances surrounding the onset and course of bereavement, they do suggest
that the time course of normal grief in the individual patient is fairly variable
and that most patients should be at, or clearly moving toward, baseline status
by the end of the first year. But specific circumstances also appear to be im-
portant. A study of 217 caregivers of family members with dementia (Schulz
et al. 2003) found that 72% of the caregivers reported feeling relief after the
death of their loved one. Their scores on the Center for Epidemiologic Stud-
ies Depression Scale increased about 50% over prebereavement scores imme-
diately after the death but returned to prebereavement levels within 15 weeks;
within 1 year, scores were below the levels reported when these persons had
been active caregivers.
Complicated Grief
A syndrome of complicated grief, which occurs in 10%–20% of bereaved in-
dividuals, has been differentiated from both normal grief (bereavement) and
clinical depression or anxiety. Proposed diagnostic criteria for this syndrome
are shown in Table 3–1. Complicated grief symptoms are clearly distinct from
normal bereavement–related depressive and anxiety symptoms and may en-
dure for several years in some cases. These symptoms predict
substantial morbidity and adverse health behaviors over and above depressive
symptoms (e.g., cardiac events, high blood pressure, cancer, ulcerative colitis,
suicidality, social dysfunction, anergia, changes in food, alcohol, and tobacco
intake, and global dysfunction) and, unlike depressive symptoms, are not ef-
fectively reduced by interpersonal psychotherapy and/or tricyclic antidepres-
sants. These findings revealed a need to identify and treat complicated grief
as a psychiatric disorder distinct from major depressive disorder (MDD).
(Prigerson and Jacobs 2001, p. 1370)
Depression Due to a General Medical Condition

DSM-IV-TR specifies that mood disorder due to a general medical condition
must be judged to be the “direct physiological consequence of a general med-
ical condition,” whereas depression that co-occurs with a general medical con-
dition, but is judged not to be a direct physiological consequence of it, is
recorded separately on Axis I, and the general medical condition is recorded on
Axis III. In the latter situation, the general medical condition may be regarded
as a “risk factor,” but in the former, it is considered a “causal factor”; however,
clear guidelines for making the distinction are lacking. Accordingly, in this sec-
tion, we ignore the distinction and consider the conditions most closely asso-
ciated with depression, regardless of the direction, if any, of causality.
Table 3–1. Proposed criteria for complicated grief

Criterion A
Person has experienced the death of a significant other, and response involves 3 of
the 4 following symptoms, experienced at least daily or to a marked degree:
1. Intrusive thoughts about the deceased
2. Yearning for the deceased
3. Searching for the deceased
4. Excessive loneliness since the death
Criterion B
In response to the death, at least 4 of the following 8 symptoms are experienced at
least daily or to a marked degree:
1. Purposelessness or feelings of futility about the future
2. Subjective sense of numbness, detachment, or absence of emotional
responsiveness
3. Difficulty acknowledging the death (e.g., disbelief )
4. Feeling that life is empty or meaningless
5. Feeling that part of oneself has died
6. Shattered worldview (e.g., lost sense of security, trust, control)
7. Assumes symptoms, or harmful behaviors of, or related to, the deceased
person
8. Excessive irritability, bitterness, or anger related to the death
Criterion C
Disturbance must endure for at least 6 months.
Criterion D
The disturbance causes clinically significant impairment in social, occupational, or
other important areas of functioning.
Source. Prigerson HG, Jacobs SC: “Caring for Bereaved Patients: ‘All the doctors just suddenly
go.’” Journal of the American Medical Association 286:1369–1376, 2001. Copyright © 2001,
American Medical Association. All rights reserved.
Chronic Illness
Major depression is a common accompaniment of many chronic medical ill-
nesses. Dunlop and colleagues (2004) studied 7,825 subjects ages 54–65 in a
national probability sample and found a strong association between chronic
illness and depression: only 3.6% of the subjects without chronic illness had
major depression, but 9.9%–18.5% of the subjects with chronic illness had
major depression. Of the conditions studied, which included arthritis, cancer,
diabetes, heart disease, hypertension, lung disease, stroke, and obesity, heart
disease and arthritis were most often associated with major depression, and
the combination of heart disease and arthritis had the strongest association of
any combination of two conditions. In the Longitudinal Aging Study Am-
sterdam (N= 2,288), Bisschop et al. (2004) also found heart disease and ar-
thritis to be most frequently associated with major depression, but the two
studies disagreed on the role of functional disability. In the former study, the
risk of major depression in both conditions (as well as in all the other condi-
tions studied) was strongly mediated by functional disability, whereas the lat-
ter study found no mediating role for functional disability in the association
between either cardiac disease or arthritis and depression.
Heart Disease
The relation between depression and ischemic heart disease is particularly
complex. Depression is a risk factor for myocardial infarction (Ariyo et al.
2000), and major depression occurring in the weeks after a myocardial infarc-
tion significantly increases 6- and 18-month mortality (Frasure-Smith et al.
1995). Moreover, patients with ischemic heart disease who are taking seroto-
nin reuptake inhibitors (but not other classes of antidepressants) have a re-
duced risk of myocardial infarction (Sauer et al. 2001). The mechanism of
this protective effect has been hypothesized to be related to the inhibiting ef-
fects of selective serotonin reuptake inhibitors on platelet aggregation, which
tends to be abnormally increased in patients with ischemic heart disease or de-
pression and even higher in patients with both diseases. This protective effect
is robust enough that some authors have proposed that selective serotonin re-
uptake inhibitors be prescribed for all patients with ischemic heart disease
(Jiang and Krishnan 2004).
Congestive heart failure is also associated with a high prevalence of de-
pression. Gottlieb et al. (2004) examined 155 patients of average age (64
[±12]) who had a mean left ventricular ejection fraction of 24. Of these pa-
tients, 46% had ischemic heart disease, and 38% were diabetic; 48% met
study criteria for depression (Beck Depression Inventory [BDI; Beck et al.
1961] score of 10 or higher). Interestingly, the depressed patients were slightly
younger than the nondepressed patients (average age= 62 vs. 65). The authors
concluded that “pharmacologic or non-pharmacologic treatment of depres-
sion could conceivably reduce morbidity and, perhaps, mortality” (p. 1548)
from congestive heart failure.
Stroke
Between 20% and 50% of stroke patients have poststroke depression, with
women about twice as likely to be affected as men (Paradiso and Robinson
1998). Of stroke patients have poststroke depression, about half have a major
depression–like syndrome that is clinically indistinguishable from primary
major depression, and the other half meet criteria for dysthymia (if the dura-
tion requirement is waived). Poststroke depression is mediated by functional
impairment (Bisschop et al. 2004), and patients with major depression fol-
lowing dominant-hemisphere stroke have more severe cognitive impairment
(Robinson et al. 1986) than is seen in stroke without depression. The effect
of poststroke depression on long-term prognosis is also negative. House and
colleagues (2001) found that major depression within 1 month poststroke
was not statistically associated with mortality at 12 and 24 months poststroke,
but the presence of depressive symptoms was associated, even after adjusting
for other confounding variables such as age and cognitive impairment. L.S.
Williams et al. (2004) analyzed a Veterans Affairs database of more than
50,000 stroke patients and found that those who received a diagnosis of de-
pression within 3 years of the stroke were 13% more likely to die during the
study period than were those who had no diagnosis of mental illness. Inter-
estingly, this study found a comparable risk of death if mental conditions
other than depression, including substance abuse, anxiety disorders, schizo-
phrenia, and personality disorder, were diagnosed within 3 years of the stroke.
Despite the well-documented clear association between stroke and depres-
sion, a systematic literature review (Hackett et al. 2004) found “no evidence
to support the routine use of pharmacotherapeutic or psychotherapeutic
treatment for depression after stroke” (p. 1).
Alzheimer’s Disease and Vascular Dementia

Although depressive symptoms are commonly seen in patients at various
stages of Alzheimer’s disease, major depression per se is relatively uncommon.
Ballard et al. (2000) found a 1-month prevalence of 8% (on the basis of
DSM-III-R criteria), compared with 19% in patients with vascular dementia.

In the Alzheimer’s disease group, depression was equally common at all sever-
ities, whereas in vascular dementia, depression was more frequent in patients
with Mini-Mental State Examination (MMSE) scores lower than 20. Vascular
dementia patients with major depression in the month prior to assessment
were significantly older, more likely to have a history of depression, and less
likely to have experienced a major stroke event than were those without major
depression. Lyketsos and colleagues (2000) reported a similar prevalence
when the Neuropsychiatric Inventory was used. They found depression in
20% of the subjects with a diagnosis of Alzheimer’s disease, compared with
32% of the participants with vascular dementia. When data for the two
groups were combined, the prevalence of depression was not related to stage
of progression of dementia.
“Vascular Depression”
Alexopoulos and colleagues (1997) have argued for the recognition of a dis-
tinct category of depression due to a general medical condition called vascular
depression; they have cited the
high rate of depression in patients with hypertension, diabetes, and coronary

disease, the high rate of depression in patients who have had a stroke, the fre-
quent occurrence of silent stroke and white matter hyperintensities in late-
onset depression, and the infrequent family history of mood disorders in de-
pression occurring in the context of silent stroke. (p. 562)
The validity of this syndrome remains controversial. Validity was supported

by de Groot and colleagues (2000), who found that elderly subjects with severe
white matter lesions (as detected by magnetic resonance imaging of the brain)
were three to five times more likely to have depressive symptoms than were
those with only mild or no white matter lesions. Mast et al. (2004) also pub-
lished supportive data. They found that geriatric rehabilitation patients with
two or three cardiovascular risk factors had greater depressive symptoms at 6-
and 18-month follow-up assessments than did patients with only one or no car-
diovascular risk factors (Mast et al. 2004). Alexopoulos et al. (1997) compared
33 elderly patients with late-onset vascular depression with a control group of
elderly depressed patients without features of vascular disease. The authors
found that those patients with vascular depression were more cognitively
impaired and more disabled, had more psychomotor retardation and less in-
sight, and had less depressed mood than those with nonvascular depression.
They hypothesized that disruption by vascular lesions of striato-pallido-
thalamo-cortical pathways may constitute the pathogenesis of depression in
such patients, and they suggested that further research may define a distinctive
pharmacological approach to the prevention and treatment of this syndrome.
This pathogenetic hypothesis was only partially supported by Thomas et
al. (2001), who studied postmortem tissue from 20 elderly patients with a his-
tory of depression and 20 with no such history. They found a significant in-
crease in atheroma overall in the depressed group (this increase was mainly a
result of the difference in the cerebral arteries and aorta) but found no evidence
for increased microvascular disease in the four neocortical lobes or within the
deep white matter of the frontal lobe.
Other studies have cast doubt on the strength of association between vas-
cular disease and late-onset depression. Stewart and colleagues (2001) exam-
ined the association between stroke, vascular risk factors, and depression in a
community-based Caribbean-born population ages 55–75 years living in the
United Kingdom. In the 287 subjects who were studied, depression (diag-
nosed with a cutoff score of 3/4 on the 10-item Geriatric Depression Scale
[GDS]) was positively associated with a history of stroke but not with other
indicators of vascular disease or risk factors for vascular disease. Kim and col-
leagues (2004) found a similar association between depression (diagnosed
with a community version of the Geriatric Mental State Schedule) and previ-
ous stroke but not other vascular risk factors (except an atherogenic lipid pro-
file) in 732 Korean subjects whose average age was 72.8. These findings did
not change when the small number of subjects who reported onset of depres-
sive episodes before age 60 were eliminated from the analysis. Cervilla and
colleagues (2004) studied genetic material from 370 subjects to determine
whether polymorphic variation at three genes (APOE, encoding for apolipo-
protein E; VLDLR, encoding for the very low-density lipoprotein cholesterol
receptor; and DCP1, encoding for angiotensin-converting enzyme) that are
related to vascular disease, and other vascular disease risk factors, determined
late-life depression. These authors found “no association between late-life de-
pression and three polymorphisms related to vascular disease. Depression was
found to be independently associated with smoking, female gender, poorer
cognitive functioning, and higher diastolic blood pressure” (p. 202). The
authors concluded that “this study does not seem to support the notion of a
specific link between the studied vascular risk factors or these vascular-related
loci and late-life depression” (p. 202), but they did not limit their sample to
subjects with late-onset depression. Finally, Devanand and colleagues (2004)
found no higher prevalence of cardiovascular disease in elderly patients with
late-onset (after age 60) as compared with early-onset major depression (but
the prevalence of vascular disease was increased in patients with late-onset
dysthymic disorder). In light of these conflicting data, “vascular depression”
remains a hypothetical entity at present.
Parkinson’s Disease
A similar prevalence of depression (i.e., about 40%) has been observed in pa-
tients with Parkinson’s disease, in a similar 50:50 ratio of major depression to
dysthymia (Nuti et al. 2004). As in stroke, depression in Parkinson’s disease
patients increases the risk for and severity of dementia and exacerbates disabil-
ity, and so is an important focus of diagnostic and therapeutic attention for
geriatric psychiatrists (Tröster et al. 2000). Treatment generally follows guide-
lines for primary mood disorder as detailed in Chapter 4 (“Mood Disorders—
Treatment”).
Substance-Induced Mood Disorder

Substance-induced mood disorder is defined in DSM-IV-TR (American Psy-
chiatric Association 2000, p. 409) as “a prominent and persistent disturbance
in mood” that is characterized by “depressed mood or markedly diminished
interest or pleasure in all, or almost all, activities” and/or “elevated, expansive,
or irritable mood” along with “evidence from the history, physical examina-
tion, or laboratory findings” that the symptoms “developed during, or within
a month of, Substance Intoxication or Withdrawal” or that “medication use
is etiologically related to the disturbance [in mood].” Substance-induced
mood disorder may not be diagnosed if depressive symptoms occur exclu-
sively during the course of a delirium. Diagnostic criteria further require that
the depression not be better accounted for by a non-substance-induced mood
disorder and that “the symptoms cause clinically significant distress or impair-
ment in social, occupational, or other important areas of functioning.”
Two broad categories of substances can be distinguished in this context.

The first comprises substances with primarily psychoactive properties that are
prone to abuse and can become addictive. This category includes alcohol; opi-
ates and related compounds such as ketamine; barbiturates; benzodiazepines
and other central nervous system depressants; stimulants, including amphet-
amines; cocaine and related compounds such as methylenedioxymethamphet-
amine (MDMA; “Ecstasy”); phencyclidine (PCP); marijuana and hashish;
hallucinogens such as lysergic acid diethylamide (LSD) and mescaline; inhal-
ants; and miscellaneous substances such as γ-hydroxybutyrate (GHB). The sec-
ond category comprises substances whose psychoactive properties are incidental
to their main therapeutic effects. This category includes numerous medications
used for acute and chronic nonpsychiatric conditions. With regard to psycho-
active substance–induced depression, Bakken and colleagues (2003) found that
48% of 241 substance abusers (age unspecified) studied at some time in their
lives had experienced a substance-induced major depression, and 41% had ex-
perienced at least one episode of dysthymia; the great majority of subjects had
also had non-substance-induced mental disorders. Comparable estimates for
nonpsychoactive substances have not been published, but case histories have
implicated all of the substances listed in Table 3–2. The critical diagnostic pro-
cedure is a careful drug ingestion history, along with detailed assessment of
mood symptoms. A depressive syndrome that begins within a month of com-
mencing regular ingestion of any of the medications listed in Table 3–2 is ade-
quate presumptive evidence to justify dosage adjustment or discontinuation,
when medically feasible, of the suspected agent.
A 75-year-old woman with no history of mood disorder denied symptoms of

depression but admitted to experiencing “waves of doom” coming over her
and fearfully described “crazy” thoughts of suicide, both feelings she had
never experienced before. She had lost almost 20 pounds in the preceding 4–
6 weeks and came to psychiatric attention when her dermatologist found her
“weeping in his waiting room.” Careful questioning determined that the
β-blocker nadolol had been prescribed for a minor cardiac dysrhythmia about
3 weeks before the onset of symptoms. All symptoms disappeared with no
specific treatment within 1 week of discontinuing the medication.
Interestingly, Ko and colleagues (2002) conducted a meta-analysis of 42

selected articles and found no association between β-blocker therapy and
Table 3–2. Medications that can cause symptoms

of depression
Analgesics
Narcotics, including synthetics
Codeine
Meperidine
Nonsteroidal anti-inflammatory agents (ibuprofen, indomethacin, naproxen)
Antiepileptic agents
Antihypertensive agents
Acetazolamide
Calcium channel blockers (e.g., diltiazem, flunarizine, nicardipine, nifedipine,
nimodipine, verapamil)
Clonidine
Guanethidine
Methyldopa
Propranolol and related β-blockersa
Reserpine
Thiazide diuretics
Antipsychotic agents, including
Phenothiazines (e.g., chlorpromazine, fluphenazine, thioridazine, thiothixene)
Haloperidol
Molindone
Anxiolytic agents, including
Alcohol
Benzodiazepines
Cancer chemotherapeutic agents
L-Asparaginase
Dactinomycin
Cisplatin
Cycloserine
Mitotane
Dacarbazine
Table 3–2. Medications that can cause symptoms

of depression (continued)
Cancer chemotherapeutic agents (continued)
Nitrogen mustard
Procarbazine
Tamoxifen
Vinblastine
Vincristine
Sedative-hypnotics, including
Barbiturates
Ethchlorvynol
Glutethimide
Methyprylon
Miscellaneous
Asparaginase
Baclofen
Cimetidine
Dexamethasone
Digoxin
Disulfiram
Isotretinoin
Levodopa
Levonorgestrel implant
Mefloquine
Methysergide
Metoclopramide
Metronidazole
Oral contraceptives
Prednisone
Ranitidine hydrochloride
Steroids
aRelatively
common offenders in the authors’ experience.
depressive symptoms. However, the studies analyzed had few elderly subjects,
and in almost every study the method of assessing depressive symptoms was
not specified. As the preceding case illustrates, merely asking elderly patients
about “depression” may elicit misleading responses.
Major Depression
Epidemiology
Major depression, as defined in DSM-IV-TR, is the most serious presentation
of primary mood disorder in the elderly. The prevalence of major depression
in the elderly has varied in large-scale studies from 1%–2% (Heithoff 1995)
to 3.7% (Steffens et al. 2000), and the prevalence appears to increase with age;
one study of subjects (average age=85) found a community prevalence of 4%
(Forsell and Winblad 1999). Depression accounts for more than 60% of
admissions to geriatric psychiatry units and is present in about 30% of elderly
patients with acute and chronic medical illnesses (Okimoto et al. 1982) and
in about 15% of nursing home residents (Falck et al. 1999).
Risk Factors
As discussed in earlier sections, chronic illness in general, a few specific illnesses,
and exposure to certain substances are clear risk factors for the onset of major
depression in the elderly. The role of stressful life events as precipitants of major
depression has been studied by several groups, although none has focused on
elderly patients per se. Kendler et al. (2003) studied 98,592 person-months in
7,322 male and female twin pairs and found that the baseline risk per month
for the onset of an episode of major depression was 0.6%. Of the stressful life
events studied (which were categorized as loss, humiliation, entrapment, and
danger), only loss and humiliation events were statistically significantly associ-
ated with onset of major depression in the month of occurrence. Loss included
death, respondent-initiated separation, and other key losses, whereas humilia-
tion included only other-initiated separation. Because old age is a time of loss,
less so of other-initiated separation, loss events likely play an increasingly signif-
icant role in the provocation of major depression in the elderly.
Diagnostic Criteria
The diagnosis of major depression in an elderly person begins with a detailed
history of the present illness, focusing on relatively abrupt changes in one or
more neurovegetative functions. For example, the patient may report that his
or her usual pattern of unsatisfactory sleep became noticeably worse around
the time that feelings of hopelessness and apathy were first experienced. Sim-
ilarly, the gradual decline in activity and appetite that had been occurring for
quite a while also may have been abruptly accelerated around the same time.
Informants such as a spouse or a child, a board and care home operator, or the
family physician can be invaluable in establishing the timing of these changes
(Wiener et al. 1997). DSM-IV-TR criteria for major depressive episode are
summarized in Table 3–3.
Major depression affects the elderly in many of the same ways that it af-
fects young adults. Nelson et al. (2005) analyzed data from 728 elderly sub-
jects with nonpsychotic major depression and found that depressed mood,
loss of interest in work and activities, psychic anxiety, somatic anxiety, lack of
energy, guilt, middle and late insomnia, and suicidal ideation best described
the presentation of depression in their subjects and were the symptoms most
sensitive to change during treatment with either sertraline or placebo. Bro-
daty et al. (1997) reported that diminished self-esteem and guilt were less
common in older depressed patients (i.e., 60 or older), but these patients had
more severe depression (higher Hamilton Rating Scale for Depression [Ham-
D] scores), more appetite loss and weight loss, and higher rates of psychotic
and melancholic depression. Caine et al. (1994) reviewed the literature and
concluded that “medical illness emerges consistently as the most common
clinical feature associated with depressive symptoms and diagnoses in com-
munity, outpatient, and inpatient samples” (p. 38). Still, accurate detection
of major depression in old age can be challenging because several features of
normal aging overlap with complaints of depression. Table 3–4 lists the most
troublesome of these normal aging changes. Signs and symptoms associated
with normal and complicated bereavement can also complicate diagnosis.
Finally, recognition and diagnosis of major depression may be complicated by
variable presentation of illness, as discussed in the following subsection.
Table 3–3. Summary of DSM-IV-TR criteria for major depressive

episode
A. Five (or more) of the following symptoms have been present during the same
2-week period and represent a change from previous functioning; at least one
is either (1) depressed mood or (2) loss of interest or pleasure.
(1) depressed mood most of the day, nearly every day
(2) markedly diminished interest or pleasure in all, or almost all, activities
most of the day, nearly every day
(3) significant weight loss when not dieting or weight gain, or decrease
or increase in appetite nearly every day
(4) insomnia or hypersomnia nearly every day
(5) psychomotor agitation or retardation nearly every day (observable by
others, not merely subjective feelings of restlessness or being slowed
down)
(6) fatigue or loss of energy nearly every day
(7) feelings of worthlessness or excessive or inappropriate guilt (which
may be delusional) nearly every day (not merely self-reproach or guilt
about being sick)
(8) diminished ability to think or concentrate, or indecisiveness, nearly
every day
(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal
ideation without a specific plan, or a suicide attempt or a specific plan
for committing suicide
B. The symptoms do not meet criteria for a mixed episode.
C. The symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
D. The symptoms are not due to the direct physiological effects of a substance or
a general medical condition.
E. The symptoms are not better accounted for by bereavement, i.e., after the loss
of a loved one, the symptoms persist for longer than 2 months or are characterized
by marked functional impairment, morbid preoccupation with worthlessness,
suicidal ideation, psychotic symptoms, or psychomotor retardation.
Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associa-
tion, 2000, p. 356. Copyright © 2000, American Psychiatric Association. Used with permission.
Table 3–4. Functional complaints common to elderly persons

Complaint Comment
Sleep disturbance Reduced total sleep time

Increased sleep latency
More frequent awakenings
More time spent in bed
Reduced sleep efficiency
Reduced appetite Reduced energy expenditure
Reduced activity
Exacerbated by diminished taste and olfactory sensation,
poor dentition, or unappealing diet
Reduced energy, Exacerbated by chronic illness, especially obstructive lung
fatigue disease and heart failure
Also exacerbated by β-blockers, clonidine, α-methyldopa,
anticonvulsants, and benzodiazepines
Impaired Normal forgetfulness may be experienced as a symptom
concentration and Exacerbated by sensory losses, especially diminished vision
memory and hearing
Exacerbated by medications with central anticholinergic
effects
Variations in Clinical Presentation

Late Versus Early Onset
Devanand et al. (2004) studied 211 patients (average age=70) who had received
diagnoses of major depression. When they used a cutoff of first episode of major
depressive disorder after age 60, they found that late-onset major depressive dis-
order was less severe (based on the 24-item Ham-D scores) and less frequently
associated with melancholia (31% vs. 50%) than was early-onset major depres-
sive disorder and that fewer than half as many late-onset patients as early-onset
patients reported a family history of mood disorder. Age, burden of medical ill-
ness (according to the Cumulative Illness Rating Scale), and presence of cardio-
vascular illness did not differentiate the early- from the late-onset cases.
Psychotic Depression
Psychotic features (delusions or hallucinations or both) occur in about 25% of
elderly patients with major depression, and in one large epidemiological survey
(N=18,980), subjects who reported feelings of worthlessness or guilt were the

most likely to have psychotic features (Ohayon and Schatzberg 2002). Most
studies find that depressive symptoms are more severe in patients with psychotic
features than in those without psychosis, but suicide attempts are probably not
more frequent (Lykouras et al. 2002). Identification of psychotic depression as
a mood disorder is relatively straightforward when symptoms occur in the
classic sequence; that is, when mood and neurovegetative changes occur before
the development of hallucinations, delusions, and bizarre behavior. The clini-
cian’s task is rendered easier still when typical depressive delusions (i.e., mood-
congruent delusions) are present or when the patient has a history of mood dis-
order. More challenging are patients in whom the presenting complaint, often
registered by family members, is of a persecutory delusion accompanied by
prominent behavior disturbance. The following cases are illustrative:
A 76-year-old woman changed apartments because she believed that her

neighbors were aware of her responsibility for the president’s “losing his veto
power,” which was going to lead to a “communist takeover.” The delusion
had emerged in the course of a series of unsatisfactory transactions with an air
conditioner repairman who had told the patient that, lacking proper parts, he
would attempt to jerry-rig something for her. By the time she was hospital-
ized, her thinking was extremely disorganized, and the term jerry-rigged had
acquired magical significance; she attributed her failure to grasp its meaning
as being directly responsible for the president’s downfall. Several days of treat-
ment with high-potency neuroleptics were required before the patient was
able to give the history of change in mood, loss of appetite and weight, and
anhedonia that accompanied and, to some extent, preceded the onset of her
delusion. She responded very well to treatment for depression.
A 72-year-old woman was an ongoing problem for neighbors and police be-
cause she was convinced that men were following her and wanted to put her
in a “car with a large dog that would attack and kill” her. Although neurolep-
tics partially controlled her fear and her bizarre behavior, her symptoms were
not completely ameliorated until antidepressant treatment was initiated, at
which time her mood also greatly improved.
Accurate diagnosis is also impeded when patients cannot or will not re-
port hallucinations or express the content of delusions and when the presence
of hallucinations or delusions must be inferred from bizarre behavior or severe
thought disorder. Near-catatonic behavioral withdrawal is one such particu-
larly common type of bizarre behavior and is often accompanied by refusal to

eat, to maintain personal grooming, or to take medications. In the absence of
a history of psychosis, late-life presentation of this syndrome should be re-
garded as psychotic depression until proven otherwise.
Masked Depression
The literature has long reflected awareness by clinicians that depression in the
elderly can be masked by physical complaints (Kielholz 1973). In the classic
version of this presentation, subjective complaints of mood changes per se are
replaced or masked by multiple somatic complaints. In the course of medical
diagnosis and treatment, these complaints are found to be either unaccompa-
nied by anatomical or physiological abnormalities or out of proportion to the
severity of these abnormalities. The prevalence of this syndrome in the elderly
is not known. One study (Posse and Hallstrom 1998) found that major de-
pression presented as somatic complaints in 13 (14%) of 93 mixed-age pri-
mary care patients, and it is likely that this proportion is higher in elderly
patients. Identification of this syndrome is particularly difficult when it occurs
in patients with somatic complaints that are associated with clear physical
causes. DSM-IV-TR criteria are usually adequate to diagnose such presenta-
tions, but the clinician must be particularly sensitive to objective indicators of
depressed mood and must investigate carefully to discern associated neuroveg-
etative features of major depression. A relatively sharp increase in the number
and severity of physical complaints at or around the time of onset of neuroveg-
etative signs, or the occurrence of physical symptoms that are illogical or that
are temporally linked to social stressors (e.g., losses) typically associated with
mood changes, can alert the clinician to the possibility of “underlying” major
depression. A perhaps more common version of this syndrome presents with a
similar acute exacerbation of physical complaints accompanied by significant
psychological distress (e.g., complaints of depression and anxiety). In this pre-
sentation, the depressive syndrome is only partially masked by the patient’s in-
sistence that the psychological distress is “because of ” the physical complaints
(Simon and VonKorff 1991).
A 90-year-old woman complained of her “arms and legs twisting,” along with
a feeling of “buzzing” from the top of her head radiating into her chest, ab-
domen, arms, and hands. She insisted that the symptoms reflected a “heart
attack” and made frequent unproductive visits to her local emergency depart-
ment. Careful interviewing found that the onset of these symptoms was asso-
ciated with marital conflict, and exacerbation tended to occur when marital
tensions escalated. Over the long run, she responded well to psychotherapy
but refused antidepressants. She eventually gained a modest degree of insight
into the functional nature of her complaints.
The variant of major depression depicted in this case differs from soma-
tization disorder with depressed mood in 1) the number of physical symp-
toms, which is typically as high as 20 or more in somatization disorder; 2) the
history, which is typically much more chronic and unremitting in somatiza-
tion disorder; and 3) the presence of neurovegetative features of depression,
which are typically not present in somatization disorder. Elderly patients with
masked depression may vary considerably in their hypochondriacal preoccu-
pation with physical symptoms. At one extreme, they may be simultaneously
disabled by but relatively indifferent to their symptoms, whereas at the other
extreme, they may have a near-delusional conviction that symptoms reflect
life-threatening illness, along with appropriate levels of psychic distress, and
may make a lifestyle of doctor and diagnostic procedure shopping. Unfortu-
nately, available data do not support precise criteria for establishing the diag-
nosis of masked depression. Indeed, Bschor (2002) has argued that the
concept of masked depression has been “abandoned” and replaced with “so-
matization disorder, somatoform disorder, psychosomatic disorder, conver-
sion disorder, neurasthenia or hypochondriasis” (p. 207). He cites
the expansion of that diagnosis onto a vast number of disorders, the continuing
lack of clarity of the concept (disorder of recognition vs. disorder of communi-
cation; the positive proof of psychic symptoms as a prerequisite vs. the positive
proof of psychic symptoms as an exclusion criterion for that diagnosis)…and
the introduction of DSM-III and ICD-10 as operationalized, purely descriptive
and rather theory-free systems of diagnostic classification (p. 207)
as reasons for its disappearance. Unfortunately, some patients still present

with multiple somatic complaints that do not meet criteria for any of the dis-
orders listed by Bschor and that dramatically melt away with appropriate an-
tidepressant treatment. We believe that a reasonable diagnostic approach is to
use DSM-IV-TR criteria (American Psychiatric Association 2000) for major
depressive episode, modifying criterion A as follows:
Five (or more) of the following symptoms have been present during the same
2-week period and represent a change from previous functioning; at least one
of the symptoms is either (1) depressed mood; (2) loss of interest or pleasure
(p. 356); or (3) persistent physical symptoms that do not meet DSM-IV-TR cri-
teria for any somatoform or other disorder, cannot be explained by structural or
functional pathology, or have a distinctly bizarre or unusual quality that is not
consistent with any known medical diagnosis. (italicized text added by authors)
Depression With Cognitive Impairment

A substantial proportion of elderly individuals with depression have concur-
rent cognitive impairment, particularly in visuospatial ability, psychomotor
speed, and executive functioning. Moreover, executive deficits in particular
may be strongly associated with late-onset depression and vegetative symp-
toms (Butters et al. 2000). Depression with functionally significant cognitive
impairment, sometimes known as depressive pseudodementia or the dementia
syndrome of depression (DSD), is distinguished from the milder, clinically si-
lent cognitive impairment associated with depression that may be detected by
neuropsychological testing. The prevalence of the former syndrome is not
well established and depends on where one draws the line defining functional
impairment.
One study of hospitalized depressed elderly patients (La Rue et al. 1986)
found that 12 of 55 scored below 23 on the MMSE, suggesting functionally
significant cognitive impairment. Milder cognitive impairment is much more
common and tends to be positively correlated with the severity of depressive
symptoms. Differentiating DSD from early dementia of the Alzheimer’s or
vascular type can be quite difficult. Patients with DSD often score in the
moderately impaired range on cognitive mental status examinations (e.g., 15–
22 on the MMSE) and may perform poorly on more detailed intellectual and
memory testing. Minor functional deficits, such as forgetting staff names or
repetitive asking of questions, also may be observed. Patients with DSD may
show poor grooming, slumped posture, and poor eye contact and may appear
to exaggerate or dramatize their cognitive deficits on mental status examina-
tion. However, they typically do not have grossly disordered behavior, such as
attempting to eat pencils, placing underwear over outerwear, climbing into
other patients’ beds, or picking at their clothing. When severely disturbed be-
havior of this type is seen in a patient who otherwise meets criteria for a mood
disorder, the presence of underlying organic brain disease or superimposed

delirium must be ruled out. Table 3–5 lists features that can help differentiate
DSD from organic dementia in troublesome cases. Because these guidelines
have not been validated by prospective investigation, they should be applied
cautiously. Often, it may be necessary to observe response to treatment before
forming a firm opinion about the presence of DSD.
In our own work in this area, we found that elderly depressed patients
with functionally significant cognitive impairment responded as well to anti-
depressant therapy as did those without cognitive impairment. However, a
lengthier and more aggressive course of treatment was required to achieve
equivalent improvement (La Rue et al. 1986). Kalayam and Alexopoulos
(1999) found that psychomotor retardation and deficits in initiation-persev-
eration predicted poorer response to treatment in elderly depressed patients,
and Alexopoulos et al. (2000) found that executive dysfunction (including
abnormal initiation and perseveration scores), but not memory impairment,
was associated with relapse and recurrence of geriatric depression. However,
Butters and colleagues (2004) failed to replicate the latter finding in a later
study with a larger series of subjects.
The relation between late-life depression, with or without DSD, and the
subsequent development of dementia and Alzheimer’s disease remains un-
clear. One study found that a substantial proportion of patients with DSD
progressed to a more profound dementia within a few years (Kral and Emery
1989), and several other studies have reported that depression per se is a risk
factor for the development of dementia. Two studies conducted in the Neth-
erlands found that depression in older patients that was not accompanied by
significant cognitive impairment at baseline predicted cognitive decline (de-
fined as a decline of 3 or more points on the MMSE) and the development
of Alzheimer’s disease at follow-up an average of 3.2 years later, but only in
subjects with more than 8 years of education. The authors interpreted the
findings to support the notion that depression is “a subclinical expression or
an early symptom of an underlying dementia process, which may become ap-
parent in a subgroup of more highly educated older people in whom com-
monly used mental status tests do not yet detect a decline from a previous
level of cognitive functioning” (Geerlings et al. 2000, p. 574). Support for
this hypothesis was provided by Wilson et al. (2002), who studied Catholic
clergymen over a 7-year period and found that scores on a modified, 10-item
Table 3–5. Differences between depression with cognitive

impairment and dementia
Depression with cognitive impairment Dementia
Clinical course and history

Onset fairly well demarcated Onset indistinct
History short History quite long before consultation
Course rapidly progressive Early deficits often go unnoticed
History of psychiatric difficulty or recent History of psychiatric problem or
life crisis emotional crisis uncommon
Clinical behavior
Detailed complaints of cognitive loss Few complaints of cognitive loss
Distress caused by cognitive problems Varied reaction to cognitive loss
Behavior does not reflect cognitive loss Behavior compatible with cognitive loss
Persistent mood disorder Mood apathetic or environmentally
responsive
Nocturnal exacerbation rare Nocturnal exacerbation common
Mood-congruent delusions Mood-incongruent delusions
Examination findings
Patients expend little effort during Patients commonly struggle to perform
examination cognitive tasks
Patients frequently answer, “I don’t know” Patients usually make an effort to answer
questions
Memory loss is inconsistent for recent and Memory impairments are greater for
remote events recent than for remote events
Patients may have specific memory gaps Patients do not have specific memory
gaps
Inconsistent performance across similar Consistently impaired performance on
types of tasks tasks of a particular ability
Prompting and semantic organization are Prompting and semantic organization
helpful in improving recall have limited benefit
Recognition memory is relatively intact Recognition memory is impaired; there
may be false-positive errors
Source. Adapted from Strub and Black 1988; Kaszniak and Christenson 1994.
Center for Epidemiologic Studies Depression Scale were associated with both
the risk of developing Alzheimer’s disease and the rate of cognitive decline.
For each depressive symptom, the risk of developing Alzheimer’s disease in-
creased by an average of 19%, and annual decline on a global cognitive mea-
sure increased by an average of 24%.
Anorexia
A less common presentation of depression in the elderly is profound anorexia,
which may occur in the absence of any other neurovegetative features of de-
pression and in the presence of what otherwise appear to be normal mood and
affect. This form of depression seems to occur mainly in the old-old and is
often accompanied by multiple chronic, often “end-stage,” medical illnesses.
It can be thought of as the “anorexia of aging” (Morley 2001), severely exac-
erbated by concomitant mood disorder, and is classified here as a form of ma-
jor depression mainly because of its severity.
The typical clinical picture is of a visibly aged, deteriorated, dysphoric pa-
tient who has “given up” and, by refusing to eat, appears to be committing
passive suicide. Hospitalization of such patients may be complicated by pas-
sive refusal of treatment and family discord around the issue of the patient’s
“right to quit”; similar ambivalence is not uncommon among treatment staff,
who may be prone to engage in prolonged discussion of the appropriateness
of hospitalization, the quality of life required to warrant aggressive treatment,
and so forth. In some patients, particularly those from non-Western cultures,
this clinical picture is interpreted by friends and family as an indication of the
patient’s wish to die, and the rendering of treatment aimed at restoring appe-
tite is regarded as an insult to the elderly patient. These and similar consider-
ations notwithstanding, a reasonable proportion of patients in this category
respond to antidepressant treatment with restoration of normal appetite,
weight gain, and the emergence of a new will to live.
Behavioral Regression
Major depression in the elderly occasionally presents with a picture of behav-
ioral regression. The patient gradually becomes less physically and socially ac-
tive, neglects personal hygiene and necessary medical treatment, loses contact
with friends and family, allows the home environment to become disordered
and filthy, and discontinues shopping and begins living off canned or other-
wise easily obtained food. On mental status examination, subjective change

in mood and anhedonia may be denied, and objective signs of depression may
be minimal. Dementia is commonly suspected in such individuals, and men-
tal status examination may indicate some of the features described in patients
with DSD. As with anorexia, response to antidepressant medications may be
dramatic.
Dysthymic Disorder
Dysthymic disorder in adults as described in DSM-IV-TR is a chronic depres-
sion of mood (for at least 2 years) that is variably accompanied by associated
symptoms of appetite disturbance, sleep disturbance, low energy or fatigue,
low self-esteem, poor concentration or difficulty making decisions, and feel-
ings of hopelessness. It occurs in about 1.8% of elderly individuals during any
given month. Dysthymic disorder is similar to but less severe and more
chronic than major depression and has a somewhat earlier onset in elderly in-
dividuals. The average age of onset of dysthymic disorder in 68 subjects over
age 55 was 31, while the average age of onset of major depression in 61 sub-
jects over age 55 was 53 (Beekman et al. 2004). Dysthymic disorder may be
preceded by an Axis I (nonmood) or Axis III disorder (“secondary dys-
thymia”), may occur as an isolated syndrome (“primary dysthymia”), or may
present as “double depression” (i.e., with major depressive disorder superim-
posed on dysthymic disorder). Kirby and colleagues (1999) studied 40 dys-
thymic individuals (average age= 74.4) and found a relatively low rate (15%)
of comorbid Axis I disorder (3 with generalized anxiety, 3 with agoraphobia
without panic) and a high prevalence of hopelessness: 47.5% felt that life was
not worth living, 17.5% expressed a death wish, and 7.5% had suicidal ide-
ation. Overall, the prevalence of dysthymic disorder, like major depressive
disorder, appears to decline with age (Beekman et al. 2004); it is more com-
mon in women, although the difference declines with age, and almost half of
elderly patients with dysthymic disorder have a history of major depressive
disorder. This figure increases to 80% if the presenting illness is “double de-
pression.” The risk of developing dysthymic disorder appears to be related to
environmental factors (e.g., relative lack of social and emotional support, his-
tory of traumatic events) and personal vulnerability factors (e.g., female sex,
family history). Age at onset also may be important; Devanand et al. (2004)
found that elderly patients with late-onset (i.e., after age 60) dysthymic dis-
order were more likely to have cardiovascular disease and less likely to have
comorbid anxiety disorder than were those with early-onset dysthymia, but
the two groups were similar otherwise.
One potential cause of a dysthymia-like syndrome is partial treatment of
major depression, either with anxiolytics alone or with inadequate doses of
antidepressants, resulting in amelioration of enough signs and symptoms as
to no longer qualify as major depression. This condition is properly termed
major depressive disorder, in partial remission (American Psychiatric Associ-
ation 2000), and is usually identifiable with an accurate treatment history.
Minor Depression
The importance of minor or “subthreshold” depression (i.e., depression that
causes clinically significant distress or impairment in social, occupational, or
other functioning but does not meet criteria for major depression or dys-
thymia) has been recognized at least since 1980, when Blazer and Williams
found that 14.7% of a community sample of subjects age 65 or older had
“substantial depressive symptoms” but only 3.7% met DSM-III (American
Psychiatric Association 1980) criteria for major depression (Blazer and Wil-
liams 1980). Interest in subthreshold depression was further stimulated by
the Epidemiologic Catchment Area studies (Regier et al. 1988), which con-
firmed Blazer and Williams’s findings of low prevalence of major depression
in this age group. These findings challenged geriatric psychiatrists to reconcile
their clinical impressions of a relatively high prevalence of mood disturbance
among the elderly with the scientific fact that major depression and dys-
thymia were actually less prevalent among the elderly than among young and
middle-aged persons.
The relatively high prevalence of what has come to be known by many
investigators as minor depression, based on criteria presented in Appendix B to
DSM-IV-TR (“Criteria Sets and Axes Provided for Further Study”), seems to
resolve this apparent contradiction. These criteria are presented in Table 3–6.
Beekman and colleagues (1997) found that minor depression, unlike major
depression, was closely associated with physical illness in elderly subjects.
However, it also was associated with as much disability (e.g., affecting general
functioning as well as specific functions such as housekeeping, socializing,
and exercising) as major depression was, even after controlling for the effects
of chronic physical illness. Minor depression also was associated with a signif-
icant (but less than in major depression) reduction in the subjective sense of
well-being, which was independent of general health status and, in a later
study, was associated with an increased risk of dying (1.80 times the risk to
nondepressed control subjects) (Penninx et al. 1999). A 10-year longitudinal
study of 131 elderly individuals with minor depression (defined by Center for
Epidemiologic Studies Depression Scale scores) found chronic illness to be a
significant risk factor for minor depression: the co-occurrence of just two dis-
eases doubled the risk for minor depression, when compared with persons
with no diseases or just one chronic disease. Functional decline also appeared
as a highly significant risk factor, especially deteriorating eyesight: people with
poorer than average visual acuity had more than twice as high a risk for minor
depression as did those with better than average eyesight. This study (Heik-
kinen and Kauppinen 2004) also found that people who had difficulties in
the use of public transport had three times the risk of minor depression com-
pared with those with no such difficulties. The authors concluded that “mi-
nor depression among the elderly is most typically a dynamic and episodic
phenomenon. Adverse life-events such as the loss of a spouse or some other
close person had predictive value for depressive symptoms in our study. We
also found the same impact from deteriorating health, deteriorating financial
situation and increased loneliness” (p. 248).
Psychotic features also have been reported in subsyndromal depression.
Ohayon and Schatzberg (2002) investigated the associations between depres-
sive symptoms and psychotic features in a sample of 18,980 subjects in five
European countries and found that as many as 10% of the subjects with just
two depressive symptoms (with or without a diagnosis of major depressive ep-
isode) had psychotic features. Other studies have generally confirmed these
findings, and in a review of this topic, Pincus and colleagues (1999) proposed
that “subthreshold” categories for all of the major phenomenological groups
of DSM-IV-TR might serve as more precise and more useful categories than
the current “adjustment disorder.”
Table 3–6. Summary of DSM-IV-TR research criteria for minor

depressive disorder
A. A mood disturbance, defined as follows:
(1) At least two (but less than five) of the following symptoms have been
present during the same 2-week period and represent a change from
previous functioning; at least one of the symptoms is either (a) or (b):
(a) depressed mood most of the day, nearly every day, as indicated by
either subjective report (e.g., feels sad or empty) or observation made
by others (e.g., appears tearful)
(b) markedly diminished interest or pleasure in all, or almost all, activities
most of the day, nearly every day (as indicated by either subjective
account or observation made by others)
(c) significant weight loss when not dieting or weight gain (e.g., a change
of more than 5% of body weight in a month), or decrease or increase
in appetite nearly every day
(d) insomnia or hypersomnia nearly every day
(e) psychomotor agitation or retardation nearly every day (observable by
others, not merely subjective feelings of restlessness or being slowed
down)
(f ) fatigue or loss of energy nearly every day
(g) feelings of worthlessness or excessive or inappropriate guilt (which
may be delusional) nearly every day (not merely self-reproach or guilt
about being sick)
(h) diminished ability to think or concentrate, or indecisiveness, nearly
every day (either by subjective account or as observed by others)
(i) recurrent thoughts of death (not just fear of dying), recurrent suicidal
ideation without a specific plan, or a suicide attempt or a specific plan
for committing suicide
(2) The symptoms cause clinically significant distress or impairment in social,
(3) The symptoms are not due to the direct physiological effects of a substance
(e.g., a drug of abuse, a medication) or a general medical condition (e.g.,
hypothyroidism).
(4) The symptoms are not better accounted for by bereavement (i.e., a normal
reaction to the death of a loved one).
B. There has never been a major depressive episode and criteria are not met for
dysthymic disorder.
Table 3–6. Summary of DSM-IV-TR research criteria for minor

depressive disorder (continued)
C. There has never been a manic episode, a mixed episode, or a hypomanic episode
and criteria are not met for cyclothymic disorder. Note: This exclusion does not
apply if all of the manic-, mixed-, or hypomanic-like episodes are substance or
treatment induced.
D. The mood disturbance does not occur exclusively during schizophrenia,
schizophreniform disorder, schizoaffective disorder, delusional disorder, or
psychotic disorder not otherwise specified.
tion, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.
Depressive Personality Disorder

As defined in DSM-IV-TR, the essential feature of depressive personality dis-
order is “a pervasive pattern of depressive cognitions and behaviors that begins
by early adulthood and that occurs in a variety of contexts” (American Psy-
chiatric Association 2000, p. 788). Elderly patients with depressive personal-
ity disorder also may have episodes meeting criteria for more specific mood
disorders, such as dysthymic disorder or major or minor depression, but even
between such episodes, these patients are dejected, discouraged, and hopeless.
A perhaps less stable but persistent variant of this condition is commonly seen
as a complication of other personality disorders, including narcissistic, bor-
derline, avoidant, and dependent personality disorder. The difficulty that pa-
tients with these personality disorders typically have in establishing and
maintaining interpersonal relationships seems to catch up with them late in
life, when they are forced to confront the loneliness and isolation that their
personality problems have caused.
Laboratory Evaluation of Depression

Laboratory evaluation of the elderly patient with clinically significant depression
is aimed at ruling out endogenous etiological or contributing factors, such as
hypothyroidism and adrenal insufficiency, and establishing the pretreatment
baseline status of physiological systems likely to be affected by psychoactive med-
ications. A recommended battery of tests with their potential uses is listed in

Table 3–7. Several laboratory procedures have been reported to be useful in es-
tablishing or ruling out a diagnosis of major depression. These include the dexa-
methasone suppression test (DST), the thyrotropin-releasing hormone (TRH)
test, and the sleep electroencephalogram. Unfortunately, the rates of false-posi-
tive and false-negative results for both the DST and the TRH test are quite high
in elderly patients. Moreover, the diagnostic confidence associated with these
tests depends on the underlying base rate (i.e., prevalence) of major depression
in the population being studied, which is typically quite variable, so neither test
is recommended for routine clinical purposes. Similarly, although the sleep elec-
troencephalogram is acceptably reliable—typically indicating an increased pro-
portion of rapid eye movement (REM) sleep (Beck et al. 1974), a longer first
REM sleep period, a shorter REM sleep latency (period of non-REM sleep be-
fore the first REM episode), and an increased density of phasic eye movements
in elderly depressed patients compared with nondepressed age-matched control
subjects (Reynolds et al. 1988)—it has not been shown to increase diagnostic ac-
curacy beyond that of the clinical evaluation alone and is too expensive to be of
widespread clinical use.
Psychological Tests
Table 3–8 lists some of the psychological assessment procedures that may be
useful in older patients whose depressive symptoms are complicated or unclear.
Psychodiagnostic tests document current mood, thought patterns, and social
tendencies and can suggest personality features that may affect the presentation
of major depression or response to treatment. For example, a Minnesota Mul-
tiphasic Personality Inventory–2 profile in which elevated scores on the hysteria
or hypochondriasis scales are combined with depressive symptoms is often ob-
served in individuals with masked depression. More generally, personality dis-
orders amplify the effect of depression and have been associated with long-term
reductions in function and quality of life.
In older patients with a combination of depressive and cognitive symptoms,
a referral for neuropsychological testing may be appropriate. Such testing provides
a detailed survey of cognitive functions, which is compared with normative values
for healthy older people and patient populations with depression or dementia (see
Chapter 5, “Dementia and Alzheimer’s Disease”). If an individual’s scores closely
Table 3–7. Screening laboratory tests for evaluation of depression

in the elderly
Test Potential diagnosis
Complete blood count with differential Folate deficiency anemia, viral infection
white blood cell count
Serum thyroid-stimulating hormone, Hypothyroidism and hyperthyroidism;
thyroxine, serum cortisol hypoadrenocorticism and
(A.M. and P.M.) hyperadrenocorticism
Sequential multiple analysis of 18 Hypercalcemia, hypokalemia,
chemical constituents of blood hyperglycemia
(SMA-18)
Urinalysis, serum urea nitrogen Uremia
Computed tomography or magnetic Brain tumor, stroke
resonance imaging of head
(as indicated by results of above tests,
physical examination)
approximate those of other depressed patients, neuropsychological findings might

serve to strengthen a clinical impression of DSD. Information on a depressed in-
dividual’s cognitive strengths and weaknesses also can be helpful for treatment
planning and psychosocial management. Because full response to antidepressant
therapies may take weeks or months, patients whose depression-related deficits in
attention, executive skills, or memory that exceed mild levels may require the sup-
port of another person to participate fully in therapies (e.g., to take medications
as prescribed or attend therapy sessions regularly), and their ability to complete
complex work assignments or self-care tasks may be undermined.
Symptom Rating Scales and Depression

Screening
Although depression rating scales were originally designed for research pur-
poses, use of such scales in clinical practice can enhance the uniformity and re-
liability of assessment. Symptom rating scales are not sufficient to establish a
diagnosis of depression, but they can help to identify individuals whose depres-
sive symptoms exceed the norm and they can provide a means of tracking treat-
Table 3–8. Psychological tests useful in assessing geriatric depression

Type of test Name of test Description Indications Outcomes Comment
Objective Minnesota Self-rated Helps establish differential Personality profile, Anchored to DSM
personality Multiphasic questionnaire diagnosis, severity of estimate of response categoriesb
Personality depression bias, diagnosis,
Inventory–2 presence of suicidality;
(MMPI-2)a may detect masked
depression,
uncooperative or
confused patient
Millon Clinical Self-rated Same as for MMPI-2 Same as for MMPI-2 Anchored to DSM
Multiaxial questionnaire Axis II categoriesb;
Inventory–III fewer data available
(MCMI-III)c for older adults
than with MMPI-2
Revised NEO Self-rated Five-dimension taxonomy Ratings on dimensions Traits (e.g.,
Personality questionnaire of personality of personality relevant neuroticism) may
Inventory to everyday coping predict use of
(NEO-PI-R) medical services,
and NEO adjustment to
Five-Factor stresses
Inventory
(NEO-FFI)d
Table 3–8. Psychological tests useful in assessing geriatric depression (continued)
Type of test Name of test Description Indications Outcomes Comment
Projective Rorschach Patient describes Same as for MMPI-2; also Description of Many older adults
personality Inkblot Teste complex useful for assessment of prominent concerns, reluctant to
unfamiliar thought disorder and in thought patterns, and respond, see test as
patterns patients unaware of or pathological too ambiguous;
unwilling to admit tendencies may give too few
psychiatric problems answers to score b
Thematic Patient creates Same as for MMPI-2 and Same as for Rorschach Geriatric version also
Apperception stories about Rorschach test, but also test availableg
Test (TAT)f pictures of identifies interpersonal
people in concerns and habits
different
situations
a
Butcher JN, Dahlstrom WB, Graham JR, et al: Manual for the Restandardized Minnesota Multiphasic Personality Inventory: MMPI-2. Minneapolis,
University of Minnesota Press, 1989.
bComputerized scoring and interpretation available.
cMillon T: Millon Clinical Multiaxial Inventory Manual, 3rd Edition. Minneapolis, MN, National Computer Systems, 1983.
d
Costa PT, McCrae RR: Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI): Professional Manual. Odessa,
FL, Psychological Assessment Resources, 1992.
eRorschach H: Psychodiagnostics: A Diagnostic Test Based on Perception. Translated by Lemkau P, Kronenburg B. Berne, Switzerland, Huber, 1942.
f
Murray HA: The Thematic Apperception Test. Cambridge, MA, Harvard University Press, 1943.
gWolk RL, Wolk RB: The Gerontological Apperception Test. New York, Behavioral Publications, 1971.
99
ment-related change. Table 3–9 lists some of the self-rated and observer-rated
scales that have proved useful in assessing severity of depression in older adults.
The GDS (Yesavage et al. 1982) is a self-rated measure developed specif-
ically for older adults (see the Appendix for GDS items and scoring instruc-
tions). Mood is extensively examined in this 30-item scale, and the questions
assess cognitive complaints and social behavior; in contrast, most somatic
items have been omitted from the GDS to prevent inflation of scores due to
normal aging changes. A simple yes-no answer format is another attractive
feature. The GDS has been shown to be reliable and valid in clinical research
with elderly medical and psychiatric patients, and it is often the standard
against which other rating scales are compared in clinical research with older
patients. A cutoff score of 11 or higher is useful in identifying persons who
may be experiencing clinically significant levels of depression and who may
benefit from more thorough diagnostic assessment. A 15-item short form of
this scale has been developed that includes most of the key items for assessing
dysphoria and hopelessness; however, it includes only a single cognitive item
that does not correlate strongly with the other cognitive items on the full
GDS (Adams et al. 2004). For most mental health assessment settings, the
full 30-item GDS is recommended. The full form typically takes 10 minutes
or less to complete, and most older adults can complete it independently or
with only brief task orientation.
The BDI (Beck et al. 1961) is another self-rated scale that has been widely
used with older adults. The BDI is particularly useful for assessing psycholog-
ical features of depression, including dysphoric mood, pessimism, self-criti-
cism, and guilt. This instrument is recommended for tracking symptom
severity in older persons with relatively clear-cut depression that is not com-
plicated by psychosis or prominent somatization. It also may help to distin-
guish normal or complicated bereavement from major depression because
bereaved individuals would not be expected to obtain high scores on items
evaluating guilt, self-criticism, or risk of suicide.
The most recent version of the BDI, the BDI-II (Beck et al. 1996), is a
21-item questionnaire that has been modified from the original to coincide
more closely with DSM-IV-TR diagnostic criteria for depression. Most items
are still rated on a 4-point scale, but rating options on the sleep and appetite
items have been expanded to allow for both increases and decreases in those
areas. Items on the initial version that pertained to body image, weight loss,
Table 3–9. Depression rating scales and screening procedures for older adults
Approximate time
Scale or procedure Type Number of items to complete (min) Recommended uses
Geriatric Depression Self-rated 30 or 15 5–10 Screening in mental

Scale (GDS) health or medical
settings; tracking
symptom changes with
treatment
Beck Depression Self-rated 21 5–10 Screening in mental
Inventory (BDI and health or medical
BDI-II) settings; tracking
symptom changes with
treatment
Hamilton Rating Scale Observer-rated, by 17–28 20–25 Screening in mental
for Depression trained professional, 17- and 21-item versions health or medical
(Ham-D) based on interview of most commonly used settings; tracking
patient symptom changes with
treatment
Cornell Scale for Observer-rated, by 19 30 Screening cognitively
Depression in trained professional; impaired patients;
Dementia both patient and tracking symptom
caregiver interviewed changes with treatment
101
Table 3–9. Depression rating scales and screening procedures for older adults (continued)

Approximate time
Scale or procedure Type Number of items to complete (min) Recommended uses
Beck Depression Self-rated 7 ≤5 Screening in medical

Inventory for Primary settings
Care (BDI-PC)
Depression items from Self-rated 9 ≤5 Screening in medical
the Patient Health settings
Questionnaire
(PHQ-9)
and somatic preoccupation were replaced in the BDI-II with questions per-
taining to agitation, concentration, and energy loss. The BDI-II and original
BDI correlate highly, but the BDI-II averages nearly 3 points higher than the
original version. Scores of 14 or higher suggest clinically significant elevations
in depression. In a study of 130 psychiatric inpatients age 55 years and older
(Steer et al. 2000), internal consistency of the BDI-II was found to be accept-
ably high, and factor analysis identified the same cognitive and noncognitive
dimensions of depression that had been previously identified in younger adult
psychiatric outpatients; scores on the BDI-II did not vary significantly with
age, sex, or ethnicity. (The BDI-II is a copyrighted instrument and is available
for purchase through the Psychological Corporation.)
Because both the GDS and the BDI-II minimize items assessing somatic
symptoms, they may underestimate the severity of depression in patients in
whom depression is expressed primarily through physical complaints or in
whom the subjective effect of the medical disorder is amplified by depression.
In general, a high score on the BDI or the GDS is useful in suggesting the
presence of depression, but somatic symptoms also must be considered before
a low score is interpreted to mean the absence of depression.
Most depression rating scales were initially studied with predominantly
white populations, so it has been unclear whether these measures are as appli-
cable to persons of different racial, ethnic, or language backgrounds. However,
translations of commonly used scales are now available, and validity studies
with diverse populations are becoming more frequent. A public access Web site
(http://www.stanford.edu/~yesavage/GDS.html) created by the authors of the
GDS provides links to translations of the scale in 24 languages, but published
information on the various translated versions varies, and users are strongly en-
couraged to contact persons responsible for translations before using translated
instruments. One small-scale study found comparable GDS scores for English-
and Spanish-speaking elderly people with and without dementia (Taussig et al.
1992). However, another study found that the GDS was ineffective in detecting
depression in elderly black persons with psychiatric disorder, perhaps because of
the paucity of somatic symptoms included in this scale (Baker et al. 1995). A
Spanish version of the BDI-II is available from the Psychological Corporation,
and translations into other languages also have been reported. In a study com-
paring white and Mexican American older adults, no differences were found in
BDI scores or reliability indices (Gatewood-Colwell et al. 1989).
Self-rated scales may not be appropriate for some elderly patients, espe-
cially those who have visual deficits, limited education, poor language profi-
ciency, psychosis, or masked depression. An observer-rated instrument, such
as the Ham-D (Hamilton 1980), is recommended for these situations. Ob-
server ratings also may be used in conjunction with patient ratings to obtain
a more complete view of symptom presentation or change. The Ham-D is
weighted toward the types of symptoms that antidepressant medications
would be expected to alter early in the course of treatment (e.g., sleep, weight
change, psychomotor speed), although it also taps depressive mood, anxiety,
and other psychological features. It has been widely used as an outcome mea-
sure in studies of efficacy of pharmacotherapies with both elderly and younger
adults. Several different cutoff scores have been used in the literature, but we
have found that scores of 16 or higher are best for detecting significant de-
pression when the 21-item scale is used. A structured interview guide that
may help to increase interrater reliability of the Ham-D has been published
(J.B. Williams 1988). The following is a sample item from this scale:
Depressed Mood (rate)
0=Absent
1=These feeling states indicated only on questioning
2=These feeling states spontaneously reported verbally
3=Communicates feeling states nonverbally, i.e., through facial expres-
sion, posture, voice and tendency to weep
4=Patient reports VIRTUALLY ONLY these feeling states in his sponta-
neous verbal and nonverbal communication. (p. 744)
Concerns have been raised about interrater reliability of the Ham-D, even
for the structured form. However, a recent study reported significantly higher
item- and total-score reliabilities for the structured interview version com-
pared with the original Ham-D, with intraclass correlations ranging from
0.78 to 1.0 for individual items (Moberg et al. 2001). Nonetheless, consider-
able training and experience are needed for this scale to yield reliable results.
Although self-rated depression scales can be used effectively by persons with
mild levels of cognitive impairment, observer-rated measures are needed for as-
sessing depression in older adults with moderate to severe cognitive impairment.
The Ham-D can be useful in some cases, but scales developed specifically for
cognitively impaired populations should be considered. The Cornell Scale for
Depression in Dementia (Alexopoulos et al. 1988) includes content similar to
that in the Ham-D, but ratings are assigned on the basis of semistructured inter-
views with both the person with dementia and his or her caregiver. Although in-
tended as a severity rating instrument once a diagnosis of depression has been
established, the Cornell scale has been shown to be effective in identifying de-
pression in nursing home patients with dementia. Internal consistency and in-
terrater reliability are acceptable when the scale is used by trained examiners.
Procedures for identifying depression in medically ill populations have re-
ceived increased attention in recent years, especially since the U.S. Preventive
Services Task Force (2002) endorsed depression screening in primary care.
Although the scales described earlier have been shown to be useful for case
finding in medically ill populations, these measures have been criticized for
including nondiscriminating items or, in the case of observer-rated scales such
as the Ham-D, for being too lengthy and impractical for most medical situa-
tions. Existing scales have been revised for medical applications, and several
new scales have been developed.
The Beck Depression Inventory for Primary Care, a seven-item version of the
BDI, has been used to screen for major depression in both primary and secondary
care settings (Beck et al. 1996). New scales include a nine-item depression module
(Kroenke et al. 2001) from the Patient Health Questionnaire (PHQ-9), and a
self-report questionnaire for medically ill persons that establishes DSM-IV psy-
chiatric diagnoses (Spitzer et al. 1999). A recent study with more than 900 elderly
patients in the multisite Improving Mood: Promoting Access to Collaborative
Treatment (IMPACT) intervention trial reported that the PHQ-9 was sensitive
and reliable in detecting depression in primary care patients and responsive to
treatment-related improvements in depressive symptoms (Löwe et al. 2004).
Other studies have shown that systematically asking even one or two questions
about mood (“Do you often feel sad or depressed?” [Mahoney et al. 1994] or
“Over the past two weeks, have you felt down, depressed, or hopeless?” and “Over
the past two weeks, have you had little interest or pleasure in doing things?”
[Whooley et al. 1997]) substantially improves identification of depressed individ-
uals in busy medical settings where time is at a premium.
Assessing Suicidality in the Elderly

One of every five suicides in the United States involves an adult age 65 years
or older (Edelstein et al. 1999). This high rate of suicide has prompted a re-
port by the surgeon general specifically targeting older adults for prevention
efforts (U.S. Public Health Service 1999). White, male, older adults are at the
greatest risk for suicide, followed by black males; white, female, older adults
have the third highest suicide rate. Other risk factors include physical illness,
especially cancer, and loss of a significant other. Older adults often use more
lethal methods than do younger adults and are less likely to directly express
suicidal ideation or to have a history of suicide attempts. Despite the obvious
importance of assessing suicidality in older persons, few interview or rating
scales have been developed to help with detection of increased suicide risk in
the elderly. The Beck Hopelessness Scale (Beck et al. 1974), a short true-false
inventory, may be helpful in this regard, and norms are available that include
some older adults; a new scale for suicidal ideation has been developed by
Beck and colleagues but has not yet been studied adequately with older
adults.
Studies have found that most older people who commit suicide consult
their primary health care providers within days or months of their deaths, so
all health care personnel must be alert to the possibility of suicide in older
adults. Screening for suicidal ideation is best accomplished as part of a general
diagnostic interview conducted by a health professional with whom the indi-
vidual has ongoing close rapport. Areas to cover include current sources of
stress, such as recent losses; signs and symptoms of depression; vague somatic
complaints or complaints of severe, unremitting pain; family and personal
history of mental health problems, including depression, alcoholism, or sub-
stance abuse; and past suicide attempts. If answers to these questions raise
concern about suicidality, direct questions should be asked to assess the sever-
ity of suicidal thoughts and any possible plan that may involve injury to self
or others. Whenever possible, family members should be interviewed for sui-
cide clues that they may have observed, such as the elder purchasing a gun,
stockpiling medications, or abruptly changing a will. Table 3–10 lists some of
the factors that have been associated with increased risk of suicide in older
adults, as well as protective factors associated with lower risk of suicide.
Holkup (2003) has provided a protocol for assessing suicidality in older
adults; although designed primarily for nurses, the concrete suggestions pro-
vided could be useful to a wide range of health professionals. Other thorough
discussions of geriatric suicide can be found in Gallagher-Thompson and Os-
good (1997) and McIntosh and colleagues (1994).
Table 3–10. Risk and protective factors for geriatric suicide

Increased risk
Age ≥75 years
Male
White
Widowed or divorced
Living alone, isolated, or recently moved
Retired or unemployed
Poor physical health, terminal illness, multiple or debilitating illnesses, or pain
Depression, substance abuse or dependence, hopelessness
History of suicide, depression, or other mental illness in close family members
Compensatory or protective
Able to learn from experience and accept help; sense of meaning in life; sense of
humor and capacity for loving; able to reminisce about positive life
experiences
History of successful transitions and coping with life challenges
Caring and available family member or supportive community network;
accessible and caring health care provider
Membership in a religious community, especially Catholic or Jewish
Source. Adapted from Holkup 2003.
Theories of Depression
The causes of clinically significant depression in the elderly are not known. A
genetic vulnerability is strongly suggested by the increased prevalence of de-
pression in the families (particularly first-degree relatives) of affected individ-
uals and is supported by evidence from twin studies (Jansson et al. 2004).
Genetic influences tend to be stronger in bipolar disorder than in unipolar
mood disorder and in early-onset cases than in late-onset cases. As discussed
earlier in this chapter (in the section “Substance-Induced Mood Disorder”
and in Table 3–2), some cases of depression in the elderly appear to be at least
partially caused or provoked by medications or other chemical agents and by
general medical conditions, such as hypothyroidism; and several other
chronic medical conditions appear to be “risk factors” for the development of
depression in old age. Three schools of thought have weighed in on the etiol-
ogy and pathogenesis of depression, and they are summarized in the following
subsections.
Psychodynamic Theories
Psychodynamic theories of depression were among the earliest published, be-
ginning with Freud’s elaborations on the theories of Karl Abraham regarding
psychopathological developments in the process of mourning. In Freud’s con-
ception, the image of the lost object (which may be an abstract object, such
as professional status) is eventually introjected and becomes part of the self.
Subsequent rage at the object—for leaving and for past hurts and disappoint-
ments—thereby becomes directed at the self. The resultant guilt, loss of self-
esteem, and need for punishment form the core of the symptom complex of
pathological grief (not to be confused with complicated grief, a clinically de-
fined condition discussed earlier in this chapter). More recently, Blatt and
Zuroff (1992) proposed that certain personality configurations are predis-
posed to depression. These configurations derive from distinct developmental
lines: the anaclitic (or dependent) line, which concerns the establishment of
satisfying interpersonal relationships, and the introjective (self-critical) line,
which focuses on the achievement of a positive and cohesive sense of self.
These configurations seem to fit well with analytical conceptualizations of ge-
riatric depression, which focus on helplessness experienced by the ego in light
of failed attempts to live up to one’s ideals, and the narcissistic injuries inevi-
tably associated with the functional declines of aging.
Loss or threatened loss during childhood also has been a focus of psycho-
dynamic formulations of depression. Although psychoanalytical theories of
depression have not emphasized late life, the relatively high frequency of
losses confronting many older individuals lends a measure of pertinence to
each of these dynamic approaches to geriatric depression. The interested
reader is directed to useful reviews by Blau (1983) and Bemporad (1988).
Cognitive and Behavioral Theories

Seligman’s concept of “learned helplessness” offers a theoretical connection be-
tween certain unavoidable losses of later life (such as declines in physical vigor,
sexual function, and general health) and the sensation of passive helplessness
often expressed by elderly depressed patients (Seligman and Maier 1967). Sim-
ilarly, cognitive theorists point to the interaction between these losses and sub-
sequent activation of deeply ingrained, stable thought schemas as resulting in
negative self-perceptions, negative interpretations of life events, and pessimism
about the future, which lead to depressed mood (Sadavoy 1994). Contem-
porary research on cognitive-behavioral therapy in late-life depression (e.g.,
Thompson et al. 2001) accepts (with little critical analysis) “negative cogni-
tions” as the proper focus of therapeutic attention, and the reported effective-
ness of cognitive-behavioral therapy indirectly supports the claim that these
cognitions play a role in the psychogenesis of depressive mood.
Neurobiological Theories
A consensus conference held by the National Institutes of Health concluded
that “the hallmark of depression in the elderly is its association with medical
comorbidity” (National Institutes of Health Consensus Conference 1992,
p. 1023). This conclusion was based on data associating late-life depression,
particularly the late-onset variant, with a broad spectrum of medical disor-
ders, including cardiovascular, cerebrovascular, musculoskeletal, metabolic,
and pulmonary illnesses and malignancies. Possible mediating mechanisms to
account for these associations have focused on cerebrovascular pathology (the
“vascular depression” hypothesis discussed earlier in the subsection “Vascular
Depression”) and on decreases in brain volume, which have been reported in
the prefrontal lobe, caudate nucleus, and hippocampus of elderly depressed
subjects. Several authors (Duman 2004; Jacobs et al. 2000) have proposed
that decreased neurogenesis contributes to hippocampal atrophy and thereby
underlies the pathophysiology of depression, and they cite several lines of in-
direct evidence in support of this theory. Other authors have challenged this
theory, however (Henn and Vollmayr 2004), and it remains provocative but
essentially untested at this time. A path analysis conducted by Kumar and col-
leagues (2000) found two distinct pathways to late-life major depression: One
path proceeded via vascular and nonvascular medical comorbidity—which
contributed equally to high-intensity lesions, which led to major depressive
disorder. The second path proceeded from frontal lobe atrophy (apparently
not consequent to medical morbidity) to late-life major depressive disorder.
Other neurobiological theories of late-life depression are similar in their
focus on central neurotransmitter function to the theories of middle-age
depression, with emphasis on the role of age-related reductions in brain concen-

trations of norepinephrine, serotonin, dopamine, and acetylcholine and age-
related increases in brain concentrations of monoamine oxidase (Lipton 1976).
The often observed temporal association between ingestion of certain medica-
tions (see Table 3–2) known to affect particular neurotransmitters and their
presynaptic and postsynaptic receptors and the onset of depressive symptoms
has provided support for several of these theories. Other investigators have stud-
ied endogenous rhythms, noting the similarity between certain abnormalities
found in depression (e.g., advances in the phase of circadian cortisol secretion,
increased body temperature, decreased nocturnal secretion of melatonin and
thyroid-stimulating hormone, changes in sleep architecture) and those seen in
normal aging (Sack et al. 1987). In adult and elderly depressed patients, abnor-
malities in brain concentrations of monoamine neurotransmitters and their me-
tabolites and in platelet α2-adrenoreceptor and 3H-imipramine binding also
have been reported (Alexopoulos 1994), but to date no single neurobiological
theory of depression in the elderly is widely accepted.
Chaisson-Stewart (1985) attempted to synthesize behavioral, cognitive, cul-
tural, and biological factors into a comprehensive model of geriatric depression
based on the work of Adolf Meyer and Sir Aubrey Lewis. In summary, her view is
that depression in the elderly represents the final result of an interaction between
biological (e.g., cerebrovascular lesions and cortical atrophy) and/or psychosocial
stressors (e.g., losses) and “defenses,” which include both learned psychological
and genetically determined psychobiological mechanisms that have been variably
weakened by age and age-related infirmity. Costa and McCrae (1994) supported
this model by arguing that “there are individual differences in the tendency to ex-
perience dysphoric affect” (p. 155). They conceptualized this tendency as an
enduring personality trait that can be measured by appropriate assessment instru-
ments and that predisposes its owner to episodes of clinical depression. This trait
is a definer of the personality factor known as neuroticism and, as such, fits neatly
into Chaisson-Stewart’s model in the place of what she calls “defenses.”
Hypomania and Mania

With or without hallucinations and delusions, signs and symptoms of elevated
mood—including reduced need for sleep, irritability, distractibility, hyperactivity,
pressured speech, flight of ideas, circumstantiality and tangentiality, grandiosity,
impulsivity, and excessive involvement in pleasurable activities that have a high

potential for painful consequence—may occur in the context of certain medical
illnesses, as an adverse reaction to certain medications or electroconvulsive ther-
apy, and as one phase (or “pole”) of bipolar disorder. Mania is diagnosed when
signs and symptoms are severe enough to cause marked impairment in occupa-
tional functioning or in usual social activities or relationships with others, when
signs and symptoms are severe enough to necessitate hospitalization to prevent
harm to self or others, or when psychotic features are present. Hypomania is diag-
nosed if the disturbance does not cause marked impairment in occupational func-
tioning or in usual social activities or relationships with others, if the disturbance
does not necessitate hospitalization, and if psychotic features are not present.
Mania Due to a General Medical Condition

Mania or hypomania due to a general medical condition may be clinically in-
distinguishable from the functional variety. Endogenous illnesses that have
been associated with the manic syndrome are listed in Table 3–11. Several in-
vestigators have suggested that mania due to a general medical condition is
more likely than primary mania to be of late onset and to occur in patients
with a negative family history, but a review of the literature by Chen and col-
leagues (1998) fails to support this claim.
Substance-Induced Mania
Substances known to induce mania include sympathomimetic agents (iproni-
azid, procarbazine), psychostimulants (e.g., amphetamines, methylphenidate,
cocaine, phencyclidine), tricyclic antidepressants, monoamine oxidase inhib-
itors, levodopa, yohimbine, bromide, alprazolam, corticosteroids, and many
other substances (Table 3–11). In this regard, hypomania or mania that be-
gins during or within 1 month of treatment with one or more of the medica-
tions listed here should be considered substance induced.
Bipolar Disorder
Epidemiology
The Epidemiologic Catchment Area study found a 1-year prevalence of 0.1% of
bipolar disorder among adults older than 65 living in the community. In light of
the 1%–2% prevalence of major depression, this finding suggests that about
Table 3–11. Medical and neurological conditions and drugs

associated with secondary mania
Category Specific agent or condition
Drugs Amphetamines, anabolic steroids, angiotensin-converting

enzyme inhibitors, antidepressants, antiepileptics,
baclofen, benzodiazepines, bromide, chloroquine,
clarithromycin, cocaine, corticosteroids, cyclobenzaprine,
dopamine agonists (bromocriptine, amantadine),
histamine H2 blockers (cimetidine, ranitidine),
hydralazine, iproniazid, isoniazid, levodopa,
metoclopramide, metrizamide, phencyclidine,
procyclidine, propafenone, selegiline, thyroxine,
yohimbine
Metabolic Hemodialysis
disturbances Postoperative state
Uremia, hyperthyroidism, pellagra, carcinoid syndrome,
hyperbaric chamber use, cyanocobalamin deficiency
Infectious diseases Influenza, Q fever

Encephalitis
Human immunodeficiency virus
Cryptococcal meningitis
Neoplasms Diencephalic glioma

Parasagittal meningioma, suprasellar diencephalic tumor,
spheno-occipital tumor
Right inferior temporal lobe glioma, bilateral orbitofrontal
meningioma
Medial frontal tumor, hypothalamic tumor
Vascular lesions Right head of caudate nucleus, thalamus, right dorsolateral

frontal cortex, right basotemporal cortex, inferior
temporal lobe
Closed head injury Temporal basal polar lesions

Right orbitofrontal white matter
Seizure disorder Right temporal focus

Table 3–11. Medical and neurological conditions and drugs

associated with secondary mania (continued)
Category Specific agent or condition
Other neurological Multiple sclerosis, Pick’s disease, Klinefelter’s syndrome,

conditions general paresis, Kleine-Levin syndrome, thalamotomy,
Huntington’s disease, Wilson’s disease
Source. Chen ST, Altshuler LL, Spar JE: “Bipolar Disorder in Late Life: A Review.” Journal of
Geriatric Psychiatry and Neurology 11:29–35, 1998. Reprinted by permission of Sage Publica-
tions, Inc.
5%–10% of elderly patients with major mood disorder have bipolar disorder.
Relatively little research has been published on bipolar disorder in the elderly.
Depp and Jeste (2004), in a review, stated, “To date, there have been no pub-
lished large-scale multi-center studies of prevalence, etiology, or clinical features
of bipolar disorder in late life, nor have there been any double-blind randomized
controlled trials of pharmacologic treatments in this population” (p. 343).
Diagnostic Criteria
DSM-IV-TR criteria for manic episode and hypomanic episode are listed in
Table 3–12 (please refer to DSM-IV-TR for criteria for the various forms of
bipolar disorder).
Clinical Presentation
Bipolar disorder typically is first diagnosed in young adulthood, but cases in
which the first episode of mania occurs after age 50 are not rare. Depp and
Jeste (2004) reviewed 13 studies of older bipolar disorder patients (sample-
weighted mean age=68.2) in which age at onset of any psychiatric illness and
of mania were reported and 8 studies in which age at onset of mania was re-
ported. The average age at onset of any mood disorder was 48, and the aver-
age age at onset of mania was 56. These ages are significantly later than the
reported age at onset of mixed-age patients with bipolar disorder, which tends
to be in the 20s. Few other consistent findings distinguish bipolar disorder in
the elderly from bipolar disorder in young and middle-aged adults, but Depp
and Jeste did conclude that older bipolar patients are less likely to have co-
morbid substance abuse than are younger patients and that late-onset mania
is associated with more neurological impairment.
Table 3–12. Summary of DSM-IV-TR criteria for manic episode

and hypomanic episode
Manic episode
A. A distinct period of abnormally and persistently elevated, expansive, or irritable

mood, lasting at least 1 week (or any duration if hospitalization is necessary).
B. During the period of mood disturbance, three (or more) of the following
symptoms have persisted (four if the mood is only irritable) and have been
present to a significant degree:
(1) inflated self-esteem or grandiosity
(2) decreased need for sleep
(3) more talkative than usual or pressure to keep talking
(4) flight of ideas or subjective experience that thoughts are racing
(5) distractibility
(6) increase in goal-directed activity or psychomotor agitation
(7) excessive involvement in pleasurable activities that have a high potential for
painful consequences
C. The symptoms do not meet criteria for a mixed episode.
D. The mood disturbance is sufficiently severe to cause marked impairment in
occupational functioning or in usual social activities or relationships with others,
or to necessitate hospitalization to prevent harm to self or others, or there are
psychotic features.
E. The symptoms are not due to the direct physiological effects of a substance or
Note: Manic-like episodes that are clearly caused by somatic antidepressant
treatment (e.g., medication, electroconvulsive therapy, light therapy) should not
count toward a diagnosis of bipolar I disorder.
Hypomanic episode
A. The same as criterion A for manic episode above, but only 4 days’ duration is
required, and the mood must be clearly different from the usual nondepressed
mood.
B. The same as criterion B for manic episode above.
C. The episode is associated with an unequivocal change in functioning that is
uncharacteristic of the person when not symptomatic.
D. The disturbance in mood and the change in functioning are observable by others.
Table 3–12. Summary of DSM-IV-TR criteria for manic episode

and hypomanic episode (continued)
Hypomanic episode (continued)
E. The episode is not severe enough to cause marked impairment in social or
occupational functioning, or to necessitate hospitalization, and there are no
psychotic features.
F. The symptoms are not due to the direct physiological effects of a substance or
Pathogenesis—Psychodynamic Theories
Relatively little has been written about the psychodynamics of hypomania
and mania in elderly patients per se. Early psychodynamic considerations
about mania compared the relative importance of predisposing personality
characteristics with that of precipitating events. Investigators such as Emil
Kraepelin were influenced by what seemed to be an inconsistent relationship
between manic episodes and external life events. Although the question re-
mains open, the psychodynamic literature from that point has generally
agreed on the primary importance of constitutional factors in the develop-
ment of the illness. Analytical theorists beginning with Abraham attempted
to understand these constitutional factors in terms of predisposing personal-
ity characteristics and the interplay of classic psychodynamic mechanisms. In
this regard, Abraham saw mania as a psychic regression to a state of intense
ambivalence directed toward love objects, reflected in behavior by primitive
impulsiveness. Later theorists conceptualized mania as a defense and tended
to see the manic personality as immature, egocentric, chronically depressed,
dependent on others for self-esteem, and dominated by feelings of interper-
sonal competitiveness and envy. Generally, psychodynamic theories of mania
have come to be seen as more relevant to shifts in mood in nonmanic individ-
uals and have largely been supplanted by neurobiological theories in attempts
to understand frank hypomania and mania.
Table 3–13. Laboratory tests for evaluation of hypomania and

mania in the elderly
Test Potential diagnosis
Blood studies
Thyroid-stimulating hormone, Hyperthyroidism
thyroxine
Cortisol (A.M. and P.M.) Hyperadrenocorticism
Sedimentation rate Collagen vascular disease, especially lupus
Lumbar puncture Encephalitis
Computed tomography or magnetic Brain tumor, stroke, multiple sclerosis
resonance imaging of head
Pathogenesis—Neurobiological Theories
A postmortem study of brain tissue (Young et al. 1994) found decreases in se-
rotonin turnover in the frontal, parietal, and temporal cortices from subjects
with bipolar disorder, as well as decreased dopamine turnover in the parietal
and occipital cortices and increased norepinephrine turnover in the thalamus
and frontal, temporal, and occipital cortices. Also, some evidence indicates
that the configuration of γ-aminobutyric acid (GABA)A receptors in the fron-
tal cortex of subjects with bipolar disorder is altered (Dean et al. 2001) com-
pared with nonbipolar subjects, but the significance of this finding remains
unclear. Similarly, changes in various neurotransmitter receptor–G-protein
interactions (which modulate neurotransmission at the intracellular level)
and certain “downstream” signal transduction components (e.g., inositol) also
have been described in subjects with bipolar disorder (Dean 2004), but no co-
herent theory has yet emerged from these findings.
Laboratory Evaluation of Hypomania and Mania

Laboratory evaluation of the elderly patient with mania or hypomania is
aimed at ruling out general medical causes such as hyperthyroidism and at es-
tablishing the pretreatment baseline status of physiological systems likely to
be affected by antimanic medications. A recommended battery of tests with
their potential uses is listed in Table 3–13.
Table 3–14. Summary of DSM-IV-TR criteria for mixed episode

A. The criteria are met both for a manic episode [Table 3–12] and for a major
depressive episode [Table 3–3] (except for duration) nearly every day during at
least a 1-week period.
B. The mood disturbance is sufficiently severe to cause marked impairment in
occupational functioning or in usual social activities or relationships with others,
or to necessitate hospitalization to prevent harm to self or others, or there are
psychotic features.
C. The symptoms are not due to the direct physiological effects of a substance (e.g.,
a drug of abuse, a medication, or other treatment) or a general medical condition
(e.g., hyperthyroidism).
Note. Mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g.,
medication, electroconvulsive therapy, light therapy) should not count towards a diagnosis of bi-
polar I disorder.
Mental Disorders, Fourth Edition, Text Revision. Washington, DC, American Psychiatric Asso-
ciation, 2000. Used with permission. Copyright 2000 American Psychiatric Association.
Mixed Mood Disorder

Elderly patients with major mood disorder commonly present with a syndrome
of mixed manic and depressive features. A typical picture might include severe
psychomotor agitation accompanied by intrusive and demanding behavior,
irritability, flight of ideas and circumstantiality, anorexia, and insomnia. The
question of whether agitated depression or mixed manic-depressive syndrome
is the correct diagnosis usually can be resolved by applying DSM-IV-TR criteria
for “mixed episode” (Table 3–14).
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4
Mood Disorders—Treatment
T reatment of mood disorders in the elderly generally follows the same prin-
ciples that apply to young and middle-aged adults but is typically complicated
by one or more of the confounding factors listed in Table 4–1. To avoid rep-
etition and redundancy, treatment trials should be conducted in a systematic
and logical sequence. For purposes of discussion, in the first part of this chapter,
we focus mainly on nonpsychotic major depression, but the treatment principles
apply, with modifications as indicated, to all of the depressive variants discussed
in Chapter 3 (“Mood Disorders—Diagnosis”). Treatment of bipolar depres-
sion is discussed at the end of the chapter in the “Bipolar Disorder” section.
Psychotherapy for Geriatric Depression

A variety of psychotherapeutic approaches can be effective with depressed older
adults. Factors that are important to consider in selecting an approach include
the nature of the problems involved; the clinical goals; the immediate situation;
and the individual patient’s characteristics, preferences, and place on the contin-
uum of care (American Psychological Association 2004). Older adults frequently
face chronic illness and disability, grief for the loss of loved ones or cherished
127
assets or roles, and demands of caregiving, and these problems often form the
content of psychotherapy. For persons with high levels of disability or recurrent
mental and physical problems, appropriate clinical goals may be to manage,
rather than eliminate, symptoms and to sustain as high a level of independence
as possible. Higher-functioning older adults often do well with the usual forms
of individual, group, or family therapies that are provided in outpatient settings.
Depressed elders with cognitive impairment may benefit more from systematic
adjustments in the social or physical environment to maximize functional skills,
behavior modification (e.g., to increase participation in pleasurable activities), or
specialized cognitive training techniques (see Chapter 6, “Other Dementias and
Delirium”). For individuals with chronic health problems or significant physical
disabilities, techniques for addressing specific medical comorbidities (e.g., pain
or insomnia) can be especially beneficial. Helping with a specific, tangible prob-
lem can strengthen the provider-patient relationship and increase the likelihood
that other issues can be successfully addressed.
Problem solving and learning new behaviors may progress more slowly with
older adults than with young or middle-aged patients (Gallagher-Thompson
and Thompson 1996). Home visits may be needed for older patients with lim-
ited mobility. For patients with memory impairment, a simple written sum-
mary of topics covered in a session can help to support continuity from one
session to the next (see Chapter 6, “Other Dementias and Delirium”). Adjust-
ments for sensory losses (e.g., amplification for hearing-impaired patients and
large-print homework or educational materials) may be required, and as dis-
cussed in Chapter 1 (“Introduction”), current cohorts of older adults may lack
familiarity with psychotherapy or may have negative attitudes toward mental
illness that need to be addressed in initial sessions.
The best-studied psychotherapeutic interventions with older adults are be-
havior therapy, cognitive-behavioral therapy, and problem-solving therapy
(Areán and Cook 2002; Gatz et al. 1998). All share a common theoretical
framework that emphasizes the importance of learning adaptive responses.
These interventions have been examined in well-controlled studies in relatively
diverse populations by several independent investigators, and clear benefits
have been shown relative to no-intervention and wait-list control subjects. In
major depression, benefits for those who respond to such therapies have been
shown to persist for at least 1–2 years. Most studies have found little difference
in efficacy between these procedures. Cognitive-behavioral therapy has been
Mood Disorders—Treatment 129
Table 4–1. Confounds in the diagnosis and treatment of

depression in elderly patients
Concurrent nonpsychotropic medications may
Cause depression
Change blood antidepressant levels
Increase antidepressant side effects
Biochemically block antidepressant effects
Require modifying the oral dose
Concurrent medical illnesses may
Cause depression biologically
Reduce the efficacy of antidepressant medication or psychotherapy
Create disability, contributing to both chronicity and reduced treatment efficacy
Increase the need for simplified medication dosing schedules (e.g., once daily)
Concurrent nonmood psychiatric conditions may
Cause depression (e.g., early Alzheimer’s disease)
Necessitate different medications
Impair participation in psychotherapy
Reduce response to antidepressant medications (e.g., personality disorder)
Worsen prognosis of the depression (e.g., alcoholism)
Other issues are that
Slower metabolism with age often requires lower doses
Transportation difficulties may restrict access to care
Increased interview time may be needed
Fixed income may limit availability of therapy and nongeneric antidepressant
medications because of cost
Source. Adapted from Rush AJ: “Overview of Treatment Options in Depressed Elderly,” in Di-
agnosis and Treatment of Depression in Late Life. Edited by Schneider LS, Reynolds CF, Lebowitz
BD, et al. Washington, DC, American Psychiatric Press, 1994, pp. 171–180. Copyright © 1994,
American Psychiatric Press. Used with permission.
adapted for use over distance (e.g., with homebound elderly) through use of
written materials and periodic telephone contacts (Landreville 1998).
Interpersonal psychotherapy, which combines elements of psychodynamic
therapy with cognitive-behavioral approaches, also has been shown to be effec-
tive in alleviating geriatric depression, but it has been studied less often than
the learning-based therapies and typically has been assessed in combination

with medication rather than as an independent therapy. Brief dynamic therapy
has been found to be effective in a few studies, but in one investigation, it was
less effective than cognitive-behavioral therapy for older adults with major de-
pression. Reminiscence therapy (Haight and Webster 1995), based on Erik-
sonian developmental theory and developed specifically for use with older
adults, also appears to have some promise for reducing depressive symptoms,
but research on this approach has been less methodologically rigorous than for
some other psychotherapy approaches. A recent study that compared reminis-
cence therapy with a social services support control condition found improve-
ment in the level of depressive symptoms and increased life satisfaction in the
reminiscence therapy group (Serrano et al. 2004).
Although individual psychotherapy has been studied most extensively,
group and family therapies are also appropriate for many older adults. Exercis-
ing care in selecting patients for group treatment is particularly important for
older patients because cognitive impairment, sensory deficits, and physical ill-
ness may limit an individual’s capacity to tolerate and benefit from group ther-
apy and may negatively influence group process. Patients with moderate to
severe cognitive impairment, psychosis, significant involuntary movements,
severe pain, or dyspnea are relatively poor candidates for group therapy.
Major depression commonly presents a crisis for families, particularly if
diagnosis and administration of treatment are significantly delayed and sig-
nificant deterioration of function is allowed to develop. By the time adequate
medical attention is obtained, the lives of two or three generations of the fam-
ily often have been considerably disrupted. Because family members are often
required to provide details of medical and psychiatric history and are fre-
quently involved in patient management (e.g., assisting with transportation,
encouraging compliance with treatment), the family therapy format is the
preferred approach in many cases (Tisher and Dean 2000).
New Directions in Psychotherapy Research

Although studies of older adults’ preferences for mental health treatments have
shown an openness to talk therapy, depressed older persons are rarely referred
for psychotherapy, and advancements in learning how best to tailor psychother-
apy techniques to serve their needs are hampered by the paucity of new studies
(e.g., in the 5 years preceding the 2002 review by Areán and Cook, only 9 psy-
chotherapy trials had been published, compared with 700 medication trials).
Additional studies of psychotherapy and combined medication and psychoso-
cial approaches are clearly needed.
One promising line of research is examining the effectiveness of brief, struc-
tured psychotherapeutic interventions for treating depression within primary
care. The multisite IMPACT (Improving Mood: Promoting Access to Collabora-
tive Treatment) project has been providing either medication, psychotherapy, or
combined therapies to depressed older adults identified in primary care (Unützer
et al. 2003). Choice of treatment is determined jointly by the patient, the primary
care provider, a depression care manager (either a nurse or a psychologist), and a
consulting psychiatrist. Problem-Solving Treatment in Primary Care (PST-PC) is
the principal psychotherapeutic intervention being studied, and it is provided by
a nurse, generally a nurse clinical specialist or psychiatric nurse practitioner. Spe-
cific problems are identified, and a seven-stage approach to problem solving is in-
troduced and practiced for each problem. Typically, one problem is addressed per
session for a total of four to eight sessions, followed by less frequent maintenance
sessions as needed. Areán and colleagues (2001) provide a more detailed descrip-
tion of PST-PC procedures suitable for older adults, and Haverkamp et al. (2004)
present a case example of its application with a chronically depressed older person.
Individuals participating in the IMPACT intervention program have experienced
significantly lower depression for at least 12 months compared with patients in
usual care, for black and Latino elderly as well as white patients (Areán et al.
2005), and despite the presence of multiple medical comorbidities (Harpole et al.
2005). Such collaborative models for intervention offer the hope of access to ef-
fective treatments for depression to a broader range of older adults and offer op-
portunities for psychiatrists with geriatric expertise to educate about depression
and other mental health conditions within a general medical context.
Other studies have been examining methods for countering older adults’
negative attitudes toward depression and its treatment and for increasing ad-
herence to recommended therapies. Dropout rates in therapeutic studies of
antidepressant medications run as high as 33%, and in clinical practice, discon-
tinuation rates of psychoactive medications are even higher (Pampallona et al.
2002). Studies of interventions aimed at helping older people adhere to medi-
cation regimens have tended to be small scale and of poor methodological qual-
ity (Higgins and Regan 2004), but most suggest that one-time, education-only
approaches are ineffective. A recent meta-analysis that focused on adherence as

an outcome in clinical trials found no difference in dropout rates between phar-
macotherapy only and combined psychotherapy and pharmacotherapy in the
short term (less than 12 weeks), but over longer periods, combination treatment
was clearly superior in reducing dropout rates (Pampallona et al. 2004). The au-
thors speculated that it may be possible to develop briefer and less expensive
“compliance-enhancing” interventions than psychotherapy per se, but they also
noted that “psychological treatment may have a stronger effect than pharmaco-
therapy on patient satisfaction and social functioning or other dimensions of
well being” (p. 718).
Combined Psychotherapy and Pharmacotherapy

Only a few studies have compared the efficacy of psychotherapy with that of
antidepressant medication in treating depression in older adults, and out-
comes have been mixed. However, the combination of antidepressant medi-
cation with psychotherapy has shown effectiveness for treatment of major
depression. This effect has been most clearly documented for interpersonal
psychotherapy, less often examined for cognitive-behavioral therapy, and not
yet investigated for some other psychotherapeutic approaches (Areán and
Cook 2002). Thase and colleagues (1997) conducted a “mega-analysis” (a
meta-analysis of their own original data) of five studies. They administered
interpersonal therapy, cognitive-behavioral therapy, and “clinical manage-
ment” to elderly patients with major depression, in various combinations
with standard pharmacotherapy, and found that psychotherapy alone was as
effective as pharmacotherapy or the combination of psychotherapy with phar-
macotherapy in patients with “mild” depression (defined as a pretreatment
Hamilton Rating Scale for Depression [Ham-D] score of 19 or less). How-
ever, patients with “severe” depression (Ham-D score of 20 or higher) did sig-
nificantly better with combination therapy (Thase et al. 1997).
Psychopharmacotherapy for Geriatric

Depression
Taylor and Doraiswamy (2004) reviewed the randomized, placebo-controlled
trials of antidepressants in populations older than 55 and found only 18 trials
that met their criteria: 12 trials studied tricyclics, 5 studied selective serotonin
reuptake inhibitors (SSRIs), 2 studied bupropion, and 1 studied mirtazapine.
They concluded that
there is a paucity of published controlled antidepressant trials in the elderly.

Most published studies examine small sample sizes and do not include com-
mon comorbid conditions. Efficacy studies examining relapse prevention are
lacking. Large placebo response rates, lack of controlled head to head com-
parisons, and other methodological design differences make cross-trial com-
parisons difficult. (p. 2285)
With this limited “evidence base” in mind, in the following section, we

review the advantages and disadvantages of currently available antidepressants
in the treatment of nonpsychotic depression, including major depression, dys-
thymia, and minor depression. Because the presence of psychosis (hallucina-
tions, delusions, severe thought disorder, or behavioral regression) appears to
significantly reduce the rate of response to antidepressant therapy, even when
concomitant antipsychotic medications are prescribed, psychotic depression
is discussed under a separate heading later in this chapter (“Psychopharmaco-
therapy for Psychotic Depression”).
The most well-studied and widely used psychopharmacotherapy for non-
psychotic depression in the elderly is the reuptake-inhibiting antidepressants—
which include the tricyclic antidepressants (TCAs), the SSRIs, and several non-
selective reuptake-inhibiting antidepressants (trazodone, bupropion, venlafax-
ine, and mirtazapine)—all of which act, at least indirectly, by blocking central
presynaptic reuptake of norepinephrine, serotonin, or both. Some also agonize
or antagonize various presynaptic and postsynaptic receptors. The controlled-
research literature indicates that these medications are about twice as effective
as placebo in elderly depressed patients and that remission rates of 65%–75%
may be expected in nonpsychotic patients, including those age 76 and older
(Gildengers et al. 2002), given an adequate trial of medication.
Because little evidence of superior efficacy of one agent over another ex-
ists, the choice of first treatment is usually based on side-effect profiles, which
are related to each agent’s affinity for central muscarinic receptors (anticho-
linergic effects), histaminic (H1) receptors (drowsiness and appetite stimula-
tion), and noradrenergic receptors (orthostatic hypotension) (Table 4–2).
Because they have a relatively low side-effect profile, and the side effects they
Table 4–2. Cyclic antidepressant receptor affinities

Agent Daily dosage (mg) H1 affinitya α1-Adrenergic affinityb Muscarinic affinityc
Amitriptyline 75–150 +++ ++++ ++++

Imipramine 75–150 ++ +++ +++
Doxepin 75–200 ++++ +++ +++
Nortriptyline 25–100 ++ +++ ++
Desipramine 75–200 + ++ ++
Sertraline 50–150 0 + +
Fluoxetine 5–20 0 0 0
Paroxetine 10–20 0 0 ++
Citalopram 20–40 + 0 0
Bupropion 150–300 0 0 0
Trazodone 150–300 +d ++++ 0
Venlafaxine 37.5–75 0 0 0
Mirtazapine 15–45 +++ e ++(?) +
Duloxetine 40–120 0 0 0
Table 4–2. Cyclic antidepressant receptor affinities (continued)
Note. 0= no effect; += weak effect; ++= moderate effect; +++= strong effect; ++++ =very strong effect.
aApproximately correlates with potential for appetite stimulation and sedation.
bApproximately correlates with potential for orthostatic hypotension.
c
Approximately correlates with potential for anticholinergic symptoms.
dDespite relatively low H affinity, trazodone is very sedating.
1
eSedative effects predominant at low doses, tend to be overcome by noradrenergic effects at higher doses.
Source. Based on data from Richelson E: “The Pharmacology of Antidepressants at the Synapse: Focus on Newer Compounds.” Journal of Clinical Psy-
chiatry 55 (suppl A):34–39, 1994; Kent JM: “SnaRIs, NaSSAs, and NaRIs: New Agents for the Treatment of Depression.” Lancet 355:911–918, 2000;
Fawcett J, Barkin RL: “Review of the Results From Clinical Studies on the Efficacy, Safety and Tolerability of Mirtazapine for the Treatment of Patients
With Major Depression.” Journal of Affective Disorders 51:267–285, 1998; and Thase ME, Tran PV, Wiltse C, et al: “Cardiovascular Profile of Duloxetine,
a Dual Reuptake Inhibitor of Serotonin and Norepinephrine.” Journal of Clinical Psychopharmacology 25:132–140, 2005.
135
Table 4–3. Advantages and disadvantages of major categories of antidepressants

Category Advantages Disadvantages
First-line agents
SSRIs Benign side effects Sexual side effects
Once-daily dosing Interact with many medications prescribed for elderly patients
Bupropion Benign side effects Three-times-daily dosing required
Relatively unlikely to cause Contraindicated in patients with seizures, eating disorder
rapid cycling
Venlafaxine Benign side effects Sexual side effects
Mirtazapine Stimulates appetite Weight gain may be a problem in the long run.
Benign side effects
Duloxetine Benign side effects Sexual side effects
Second-line agents
Tricyclics May be more effective than Dangerous side effects:
nontricyclics in severe depression Orthostatic hypotension
Inexpensive Delayed cardiac conduction
Once-daily dosing
Trazodone Inexpensive Dangerous side effects:
Orthostatic hypotension
Can cause priapism, although rare
Table 4–3. Advantages and disadvantages of major categories of antidepressants (continued)
Category Advantages Disadvantages
Third-line agents
MAOIs Inexpensive Dietary and medication restrictions required
Effective in atypical depression Potentially fatal interaction with meperidine, sympathomimetics,
SSRIs
Lithium Inexpensive Only two-thirds as effective as above agents
Psychostimulants Immediately effective No controlled studies
(methylphenidate, Benign side effects Development of tolerance common
amphetamines)
Note. MAOIs= monoamine oxidase inhibitors; SSRIs =selective serotonin reuptake inhibitors.
137
do cause tend to be less dangerous than those caused by tricyclics, the SSRIs
(including fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and
escitalopram) and the nonselective amine inhibitors bupropion, venlafaxine,
and mirtazapine are generally preferable to the TCAs and are therefore re-
garded here as first-line agents. It must be noted that some authorities still pre-
fer TCAs in patients with severe, melancholic depression; however, even these
experts avoid the tertiary tricyclics (e.g., amitriptyline, imipramine, doxepin,
trimipramine) because of their greater sedating, anticholinergic, and cardiac
side effects and their relatively greater tendency to cause orthostatic hypo-
tension than their demethylated counterparts, the secondary tricyclics (e.g.,
desipramine, nortriptyline, protriptyline). All TCAs have type 1 antiarrhyth-
mic effects and are relatively contraindicated in patients with ischemic heart
disease or preexisting cardiac conduction disturbance (increased P-R interval,
bundle-branch block, increased QRS). Trazodone is an effective and safe an-
tidepressant in the elderly, but it is sedating enough to be difficult for many
elderly patients to tolerate in effective doses and thus is regarded along with
the tricyclics as a second-line agent in the discussion below and in the sum-
mary presented in Table 4–3.
Because the tetracyclic agent maprotiline has a relatively strong associa-
tion with seizures and has no advantages that are not matched by other less
risky agents, it is not recommended for elderly patients. Similarly, the diben-
zoxazepine amoxapine has mixed neuroleptic-antidepressant properties and
attendant risks of extrapyramidal symptoms and tardive dyskinesia and is not
recommended.
First-Line Agents—Selective Serotonin Reuptake

Inhibitors
SSRIs have been studied in elderly depressed patients and have been shown
to be effective and generally well tolerated and to have few side effects (New-
house 1996). Some side effects, such as mild anorexia, nausea, gastrointestinal
upset, jitteriness, and headache, typically diminish within the first few days
to weeks of initiation of therapy; others, such as sexual dysfunction (including
inhibited desire, delayed ejaculation, and anorgasmia) and later-onset weight
gain, may not diminish at all.
The SSRIs all competitively inhibit several cytochrome P450 (CYP)
isoenzymes that are responsible for the hepatic metabolism of several pharma-
ceutical agents (Table 4–4); the SSRIs can therefore cause clinically significant
increases in serum levels of other medications if administered concurrently. In
this regard, paroxetine is the most potent, followed by fluoxetine, sertraline,
citalopram, escitalopram, and fluvoxamine. SSRIs all have an elimination
half-life of about 1 day, except fluoxetine, which has a significantly longer
half-life (discussed in the following subsection). Fluoxetine, paroxetine, and,
to a lesser extent, fluvoxamine (but not citalopram, escitalopram, or sertra-
line) inhibit their own metabolism, producing nonlinear increases in plasma
concentrations with dosage increases. SSRIs also attenuate platelet activation
by depleting serotonin storage and have been shown in at least one study
(Sauer et al. 2003) to reduce the risk of myocardial infarction, although the
effect is modest.
Citalopram is metabolized predominantly by the CYP isoenzymes 2C19
and 3A4, and at least six polymorphisms of 2C19 that result in slowed me-
tabolism of citalopram have been identified. Patients with these phenotypes
will have higher blood levels of citalopram at any given dose than will patients
with the wild-type allele, and dosages must be adjusted accordingly. Although
there is no practical way to determine any given patient’s 2C19 phenotype,
the “slow metabolizer” variant is present in about 13%–23% of individuals of
Asian descent and in only 2%–5% of non-Asian persons (Yu et al. 2003).
All of the SSRIs can produce serious, potentially fatal interactions with
monoamine oxidase inhibitors (MAOIs) and should not be administered
within 2 weeks of discontinuation of an MAOI; similarly fatal interactions
have been reported with the antihistamines terfenadine and astemizole, both
of which have been withdrawn from the U.S. market but are still available in
other countries.
Fluoxetine
Advantages. Fluoxetine has mild psychostimulant-like effects and is very
weakly anticholinergic. As is true of the other SSRIs, the final dosage of
20 mg/day (for the vast majority of patients) is only twice the recommended
starting dosage of 10 mg/day, which vastly simplifies the process of dosage ad-
justment in the induction phase of therapy.
Disadvantages. Stimulant-like properties may interfere with sleep and appe-
tite, particularly in the first few weeks of therapy. Fluoxetine has a long elimi-
Table 4–4. Psychotropic medications that inhibit or induce cytochrome P450 (CYP)

isoenzymes
CYP isoenzyme
Psychotropic agent affected Effect
Inhibitors 2D6 May increase levels of

Antidepressants Antidepressants: Amitriptyline, imipramine, nortriptyline, desipramine, clomipramine,
Fluoxetinea venlafaxine, paroxetine
Paroxetinea Antipsychotics: Haloperidol, chlorpromazine, perphenazine, thioridazine, clozapine,
Clomipramine risperidone, fluphenazine
Sertraline ACE inhibitors: Captopril
Citalopram Antihistamines: Chlorpheniramine
Antipsychotics β-Blockers: Propranolol, metoprolol, propafenone, timolol
Haloperidol Opioids: Codeine, hydrocodone
Others: Dextromethorphan, tramadol, ondansetron, tamoxifen
Inhibitors 3A4 Inhibitors will raise, inducers will lower levels of
Antidepressants Antidepressants: Amitriptyline, imipramine, sertraline, citalopram, trazodone
Fluoxetinea Benzodiazepines: Diazepam, alprazolam, triazolam, midazolam
Fluvoxaminea Hypnotics: Zolpidem
Sertraline Antihistamines: Loratadine, astemizoleb
Inducers Calcium channel blockers: Diltiazem, felodipine, nifedipine, verapamil
Anticonvulsants Others: Amiodarone, aripiprazole, astemizole,b carbamazepine, cisapride,b
Carbamazepine erythromycin, clarithromycin, pimozide,b propafenone, terfenadine,b quinidine,
Phenobarbital lovastatin, corticosteroids, quetiapine
Table 4–4. Psychotropic medications that inhibit or induce cytochrome P450 (CYP)
isoenzymes (continued)
CYP isoenzyme
Psychotropic agent affected Effect
Inducers (continued)
Antidepressants 1A2 May lower levels of
Citalopram Antidepressants: Amitriptyline, imipramine, fluvoxamine
Fluvoxaminea Antipsychotics: Phenothiazines, haloperidol, clozapine
Others: Acetaminophen, caffeine, ciprofloxacin, estradiol, theophylline, warfarin
Antidepressants 2C9 May lower levels of
Fluoxetinea Diclofenac, ibuprofen, naproxen, phenytoin, warfarin
Fluvoxaminea
Sertraline
Antidepressants 2C19 May lower levels of
Fluoxetine Antidepressants: Amitriptyline, clomipramine
Fluvoxaminea Proton pump inhibitors: Omeprazole, lansoprazole, pantoprazole
Others: Diazepam, phenytoin, progesterone
Note. ACE =angiotensin-converting enzyme.
a
Relatively more potent inhibitor.
bAdministration of nefazodone (or other nonpsychotropic inhibitors of CYP isoenzyme 3A4) with these agents may lead to potentially fatal torsades de
pointes ventricular arrhythmia.
141
nation half-life (more than 24 hours) and has at least one active metabolite
(norfluoxetine) with a half-life of up to 15 days. Therefore, at least 5 weeks must
elapse after discontinuing fluoxetine therapy before an MAOI can be safely ad-
ministered.
Sertraline
Advantages. Sertraline has a relatively low potential for competitive inhibi-
tion of any of the CYP isoenzymes and is therefore a good choice for patients
taking complex multidrug regimens. It is also a relatively potent reuptake inhib-
itor of dopamine, at least in vitro, and may have theoretical advantages in pa-
tients with Parkinson’s disease, although several authorities recommend against
the use of SSRIs in such patients because of the risk of confusion. Sertraline has
the most linear dose–plasma level relation of the SSRIs.
Disadvantages. Possibly because of its dopaminergic properties, sertraline is
somewhat stimulating and may interfere with sleep if administered late in the
day.
Paroxetine
Advantages. Paroxetine has no active metabolites and is less activating than
either fluoxetine or sertraline and therefore may be given at bedtime.
Disadvantages. Paroxetine causes relatively potent inhibition of CYP2D6 and
therefore may pose a problem for patients taking multidrug regimens. It also has
mild anticholinergic effects, but a study conducted by Nebes and colleagues
(1999) showed that “the slight increase in serum anticholinergicity seen in some
elderly patients treated with paroxetine did not significantly impair cognitive
function, even in patients with a preexisting cognitive impairment” (p. 26).
Fluvoxamine
Advantages. Fluvoxamine is the most sedating of the SSRIs and may be ad-
ministered at bedtime.
Disadvantages. Fluvoxamine causes potentially clinically significant inhibition
of CYP1A2 and CYP2C19 (and probably a third, CYP3A3/4) and therefore may
elevate serum levels of propranolol and omeprazole, as well as citalopram and ven-
lafaxine. It has been studied relatively little in geriatric depression.
Citalopram
Advantages. Citalopram is a very weak inhibitor of all the CYP isoenzymes
and therefore is the SSRI of choice for patients with complex multidrug reg-
imens. It has mild gastrointestinal side effects associated with all of the SSRIs
(nausea, diarrhea), which appear to be less frequent in elderly than in middle-
aged patients; a weak tendency to cause bradycardia (in about 2%–3% of pa-
tients) appears to increase with age.
Disadvantages. Citalopram is contraindicated in patients receiving pimozide.
An incompletely understood interaction results in significant increases in the
QTc interval, with consequent risk of serious arrhythmia.
Escitalopram
Advantages. Escitalopram, the S-enantiomer of citalopram, is similar to ci-
talopram but more selective and may cause side effects less frequently than
does citalopram.
Disadvantages. Few studies on escitalopram have been done to date in el-
derly patients.
First-Line Agents—Non–Selective Serotonin Reuptake

Inhibitors
Bupropion
Advantages. The dopaminergic properties of bupropion may be beneficial
for patients with Parkinson’s disease. It does not cause sexual side effects or
orthostatic hypotension, and it is very safe in overdose. It does not cause
weight gain; a review (Settle et al. 1999) of three clinical trials found that the
sustained-release form of bupropion produced dose-related weight loss in all
three studies.
Disadvantages. Bupropion must be given in divided doses at least 4 hours
apart (usually three times a day), and no single dose may be greater than
150 mg; the extended-action form (Wellbutrin SR) may be given twice a day,
and the Wellbutrin extended-release version is given once daily. Bupropion is
contraindicated in patients with seizure disorder, even if only by history, or in
patients with a history or current diagnosis of anorexia or bulimia. Significant
inhibition of CYP2D6 may result in increased blood levels of certain anti-

psychotic medications, β-blockers, and type 1C antiarrhythmic agents.
Venlafaxine
Advantages. Although venlafaxine blocks reuptake of serotonin and nor-
epinephrine, its side-effect profile is generally benign and very similar to that
of the SSRIs, making it one of the preferred therapeutic agents in the elderly.
One study (Trick et al. 2004) found that venlafaxine actually increased the
“critical flicker fusion” threshold in 88 depressed patients (average age=71),
whereas the comparator medication, dothiepin (a TCA not available in the
United States), reduced the critical flicker fusion threshold. The authors con-
cluded that venlafaxine does not cause cognitive impairment in elderly pa-
tients.
Disadvantages. The advantages notwithstanding, sexual dysfunction,
weight gain, and gastrointestinal upset are seen fairly commonly. Venlafaxine
also causes supine blood pressure elevations in 3%–5% of patients, so moni-
toring is advisable in the early phases of treatment. Downward adjustment of
dosage is recommended in patients with liver or kidney disease.
Mirtazapine
Advantages. Mirtazapine is an atypical antidepressant with α 2-adrenergic
antagonist and serotonin type 2 and type 3 receptor–blocking activity. It is
well tolerated and has few side effects other than sedation, which tends to di-
minish as the dosage is increased and noradrenergic effects overcome antihis-
taminic effects. One controlled study comparing mirtazapine with paroxetine
in elderly patients found that mirtazapine produced an earlier therapeutic re-
sponse, had fewer side effects in general, and resulted in significantly more
weight gain than did paroxetine (Schatzberg et al. 2002). The latter effect is
consistent with clinical experience suggesting that mirtazapine is particularly
effective as an appetite stimulant in elderly depressed patients with poor ap-
petite and weight loss.
Disadvantages. Weight gain may be intolerable for many patients. Only
one double-blind, placebo-controlled study in elderly patients has been pub-
lished to date.
Duloxetine
Advantages. Duloxetine is an inhibitor of norepinephrine and serotonin re-
uptake and has been shown to be effective for depression, neuropathic pain,
and stress urinary incontinence in women.
Disadvantages. Data on duloxetine in elderly depressed subjects are lacking
to date.
Second-Line Agents—Tricyclic Antidepressants

TCAs produce side effects that warrant a pretreatment evaluation whenever
possible. The physical examination is specifically oriented toward detection of
signs of narrow-angle glaucoma, prostatism, and xerostomia, all of which may
be aggravated by anticholinergic effects of TCAs, and congestive heart failure,
which may predispose to the development of significant orthostatic hypoten-
sion. A 12-lead electrocardiogram is obtained to determine the presence of car-
diac conduction disturbance and ischemic heart disease. Although bundle-
branch block presents the greatest risk for development of complete heart
block, caution is also recommended in patients with first-degree block (i.e.,
prolonged P-R interval) and prolonged QRS interval. Other potentially im-
portant findings include sinus node dysfunction (sick sinus syndrome), which
precludes augmentation with lithium salts (see “Pretreatment Evaluation—
Lithium Therapy” subsection later in this chapter), and supraventricular ar-
rhythmia, which could be aggravated by anticholinergic effects of TCAs.
Roose and Glassman (1994) originally raised the possibility that because TCAs
have type 1A antiarrhythmic properties, these drugs may increase the risk of
sudden death in patients with arrhythmia of any type or who have had myo-
cardial infarction. Finally, liver function tests (e.g., bilirubin, aspartate trans-
aminase [AST], alanine transaminase [ALT], and alkaline phosphatase) also
are obtained because significant hepatic disease is a relative contraindication to
use of TCAs and may lead to very high serum levels and possible toxicity.
Nortriptyline
Advantages. Reynolds and colleagues (Reynolds et al. 1999; Thase et al.
1997) published results of a series of very-well-designed treatment studies
with elderly subjects that clearly showed the safety and efficacy of nortrip-
tyline, administered in dosages adjusted to achieve plasma levels between 80

and 120 ng/mL, for treatment of major depression.
Disadvantages. Nortriptyline has the side effects and cardiac risks described
earlier for TCAs as a group.
Desipramine
Advantages. Desipramine has a low side-effect profile, is relatively activat-
ing, and is generally well tolerated. In nonelderly adults, desipramine appears
to have a roughly linear serum level response relation (i.e., no therapeutic
window), with the likelihood of response increasing as serum level rises above
115 ng/mL (Nelson et al. 1982). Thompson et al. (2001), in the absence of
desipramine levels for all subjects, found that desipramine in dosages at or
greater than 100 mg/day (when combined with cognitive-behavioral ther-
apy), was more effective than either desipramine alone or cognitive-behav-
ioral therapy alone in subjects with an average age of approximately 67; lower
desipramine dosages did not appear to be effective. Response to desipramine
may be predicted by a methylphenidate challenge (see “Predictors of Response
to Cyclic Antidepressants” later in this chapter).
Disadvantages. Desipramine is not as well studied as nortriptyline, espe-
cially in patients with cardiac conduction disturbance and congestive heart
failure, and it may not be as safe as nortriptyline. As a purely noradrenergic
agent, desipramine may be less effective in patients whose depression re-
sponds better to a mixed noradrenergic-serotonergic agent such as nortrip-
tyline.
Second-Line Agents—Nontricyclics
Trazodone
Advantages. Trazodone has no anticholinergic effects and is extremely se-
dating, so it may have a role in the treatment of patients with significant sleep
disturbance.
Disadvantages. Trazodone may cause mild gastrointestinal upset and ortho-
static hypotension. Its sedative properties limit its usefulness in many patients.
Predictors of Response to Cyclic Antidepressants

Several clinical and demographic factors have been studied as possible predic-
tors of response to treatment of acute depression in the elderly. Age at onset
of illness has produced conflicting results. In one study, patients with early-
onset depressive disorder who received treatment with nortriptyline and in-
terpersonal therapy achieved remission of the index episode more slowly
(Reynolds et al. 1998); in another study, later age at onset was the strongest
predictor of slow recovery (Alexopoulos et al. 1996). In the latter study, age
and chronicity of episode were also significantly associated with time to re-
covery. In a study conducted by Flint and Rifat (1997), high baseline anxiety
level was associated with delayed response (median of 5 weeks vs. 4 weeks for
patients with low anxiety scores), whereas hospitalization for the index epi-
sode of depression and attempted suicide predicted shorter time to response.
Cognitive dysfunction also may affect treatment response. Kalayam and
Alexopoulos (1999) found that depressed patients who remained symptom-
atic after treatment had more abnormal initiation and perseveration scores
and longer P300 latency (elapsed time between a stimulus and the occurrence
of one voltage peak in a cortical evoked potential) compared with control sub-
jects and depressed patients who achieved remission. The researchers con-
cluded that prefrontal dysfunction was associated with poor or delayed
antidepressant response in depressed elderly patients.
Specific laboratory measures and the interaction between specific life
events and personality–cognitive characteristics (Mazure et al. 2000) have
been reported to have predictive power with respect to subsequent antidepres-
sant response. These laboratory measures include serum cortisol response to
administration of oral dexamethasone (Spar and La Rue 1983); pretreatment
measures of orthostatic hypotension (Diehl et al. 1993; Jarvik et al. 1983); re-
sponse to a test dose of methylphenidate (Spar and La Rue 1985); pretreat-
ment red blood cell counts (Mentre et al. 1998); pretreatment folate blood
levels (Alpert et al. 2003); specific polymorphisms of the norepinephrine
transporter gene (Yoshida et al. 2004); subacute reduction in prefrontal cor-
tical activity per quantitative electroencephalography (Cook and Leuchter
2001); and dopaminergic supersensitivity as measured by the apomorphine
challenge test (Healy and McKeon 2000). However, none of these laboratory
measures has yet gained widespread clinical utility.
Initiation and Dosage Adjustment of Cyclic

Antidepressant Therapy
In general, starting dosages for SSRIs and other non-TCA agents are half the
usual adult dosage and are increased, as side effects allow, to the full adult dos-
age within the first week or two of therapy. This dosage is maintained for
6 weeks before dosage increase is considered. The likelihood of obtaining im-
proved response by increasing the dosage beyond the recommended level is
generally low, but an increase is worth trying because the side effects of these
agents are so benign. Initiation of TCA therapy follows the same guidelines
but typically calls for a gradual increase of dosage, as limited by side effects,
to produce a plasma level of 80–120 ng/mL for nortriptyline, or the highest
dosage that is safely tolerated for the other TCAs. Compliance is usually en-
hanced by minimizing the number of doses administered during any 24-hour
period. In this regard, most of the antidepressants discussed in this chapter
have an elimination half-life of about 24 hours and can be administered in a
single dose, preferably in the morning for the activating agents such as flu-
oxetine or at bedtime for the sedating agents such as trazodone, paroxetine,
fluvoxamine, mirtazapine, and the TCAs. Sertraline, citalopram, and escitalo-
pram activate some patients and sedate others, so the timing of dosage is by
trial and error. Venlafaxine and bupropion must be administered in divided
doses; bedtime doses of venlafaxine are generally well tolerated, but bupro-
pion is quite activating, and the last daily dose should not be given after 4:00
or 5:00 P.M.
Management of Cyclic Antidepressant Side Effects

Most side effects caused by non-TCA agents are managed symptomatically;
for example, antacids for nausea and analgesics for headache are often effec-
tive. Sexual side effects of SSRIs, which have been reported in up to 50% of
adults, may respond to treatment with cyproheptadine, amantadine, yohim-
bine, bupropion, or central nervous system stimulants such as methylpheni-
date, but controlled studies are lacking (Ashton and Rosen 1998; Woodrum
and Brown 1998). No effective treatment, other than dosage reduction or
switching to another class of antidepressant, has been reported for SSRI-
induced weight gain.
Side effects of TCAs include anticholinergic effects (dry mouth, constipa-

tion, blurry vision, urinary hesitancy, and delirium) and orthostatic hypo-
tension. Most of the anticholinergic effects can be managed with dosage
adjustment and adjunctive agents. Dry mouth is relieved by sucking on hard,
preferably sugarless candies or by chewing gum. A 1% solution of pilocarpine
used as a mouthwash every 3 or 4 hours also has been reported to be helpful
(Bernstein 1983). Constipation can be managed with stool softeners, bulk lax-
atives, and adequate fluid intake. Blurry vision may respond to 1% pilocarpine
eyedrops, one drop every 4–6 hours as needed. In milder cases, artificial tears
usually suffice. Urinary hesitancy is often responsive to oral bethanechol, 10–
30 mg three times a day. Patients, particularly men, are instructed to be aware
of the possibility of complete urinary obstruction and to have appropriate plans
should complete obstruction occur (e.g., to report to the nearest emergency de-
partment). Delirium can be life threatening and is usually responsive to discon-
tinuation of the offending agent and supportive treatment. In the extreme case,
1–2 mg of physostigmine administered by slow intravenous push is effective.
Orthostatic hypotension is a more difficult problem. This symptom tends to
occur early in treatment and appears to be a “threshold” phenomenon that oc-
curs at a certain dosage but does not necessarily worsen if the dosage is in-
creased. Because it is worsened by dehydration and by pooling of blood in the
lower extremities, orthostatic hypotension may be ameliorated by increasing
salt in the patient’s diet or by administering small doses of salt-retaining steroids
(e.g., 0.025–0.05 mg of fluorohydrocortisone). Support hose can be helpful, as
can careful, repeated patient instruction in arising slowly and holding on to
something stable for support.
Third-Line Agents—Monoamine Oxidase Inhibitors

Third-line agents are usually reserved for patients who have not responded to
first- and second-line treatments or who have a history of good response to
agents in this class. MAOIs irreversibly inhibit monoamine oxidase (MAO), the
enzyme responsible for synaptic degradation of the monoamine neurotransmit-
ters norepinephrine, dopamine, and serotonin. MAO occurs in two forms,
called MAO A and MAO B. MAO A is found in brain only and primarily ox-
idizes dopamine, and MAO B is found in both brain and gut and oxidizes nor-
epinephrine, serotonin, and dopamine. MAOIs have not been as well studied
as cyclic antidepressants in elderly patients, but they appear to be as effective

(Georgotas et al. 1986). In the United States, phenelzine and tranylcypromine
are available for treatment of depression, and selegiline, which selectively inhib-
its MAO B, is marketed primarily for adjunctive treatment of Parkinson’s dis-
ease but also has been studied in depression. Moclobemide, one of the first
reversible inhibitors of MAO A, is available in Canada but not in the United
States at the time of this writing.
Phenelzine is administered at an initial dosage of 15 mg twice a day, gradu-
ally increasing to a maximum of 60–75 mg/day; tranylcypromine is adminis-
tered at an initial dosage of 10 mg twice a day, increasing to a maximum of
50 mg/day. Selegiline is administered at dosages of 5–15 mg/day (with levodopa)
for Parkinson’s disease; at this dosage, it is selective for MAO B and enhances
dopaminergic transmission. But at antidepressant dosages (i.e., 40 mg/day), it
loses this selectivity. Each of these agents is relatively free of sedative and anticho-
linergic effects and does not appear to affect cardiac conduction. These agents do
cause orthostatic hypotension, however, and in the presence of sympathomi-
metic drugs, dietary monoamine precursors such as tryptophan or naturally oc-
curring pressor substances such as tyramine, phenelzine, and tranylcypromine
can cause severe hypertensive reactions that can be life threatening. Because of
these properties, patients taking these MAOIs need to be on restricted diets and need
to be strongly cautioned against ingesting certain drugs. Selegiline does not interact
with dietary amines at low dosages, but it probably does interact at antidepressant
dosages. Orthostatic hypotension from MAOIs is somewhat different from that
produced by TCAs in that it tends to be dose related, occurs later in therapy, and
may gradually subside at a fixed dosage.
Phenelzine
Advantages. Phenelzine is nonstimulating and may be mildly sedating.
Disadvantages. Phenelzine causes irreversible degradation of MAO and
therefore may continue to exert effects for 2 weeks or longer after discontin-
uation of administration, as total body MAO is gradually replaced.
Tranylcypromine
Advantages. Tranylcypromine is mildly stimulating and may be preferable
for patients with psychomotor retardation. It is more reversibly bound to
MAO and therefore requires only a 1-week washout period before sympatho-
mimetic agents or diet ad libitum can be administered safely.
Disadvantages. Because of its psychostimulant effects, tranylcypromine
may have greater abuse potential than phenelzine.
Selegiline
Advantages. As mentioned, selegiline is selective for MAO B and will not
interact with dietary tyramine in low dosages. However, it is probably not, by
itself, an antidepressant at these dosages.
Disadvantages. Selegiline is poorly studied at antidepressant dosages and,
like all MAOIs, is prone to potentially dangerous interactions with other
drugs.
Moclobemide
Advantages. Moclobemide is selective for MAO A and does not require di-
etary restriction. It has been well studied as an antidepressant, including in
elderly subjects, and has been shown to be comparable to TCAs and SSRIs in
efficacy (Amrein et al. 1997). Reversibility of MAO inhibition makes it less
likely to pose a problem interacting with other agents.
Disadvantages. Like all MAOIs, moclobemide is prone to potentially dan-
gerous interactions with other drugs.
General Principles of Treatment With MAOIs
Pretreatment physical and laboratory examinations should be conducted as
described earlier for cyclic antidepressants, including determination of pre-
treatment orthostatic changes in blood pressure and, based on the medical
history and physical examination, assessment of the patient’s likelihood of re-
quiring sympathomimetic agents. Elderly patients with chronic asthma or
bronchitis who must take indirect-acting bronchodilators and patients with
Parkinson’s disease who may require treatment with levodopa are not candi-
dates for MAOI therapy. The patient’s reliability vis-à-vis dietary and medi-
cation restrictions must be assessed carefully. Specifically, patients who have
dementia and who are monitoring their own diet and medications are poor
candidates for MAOI therapy.
Initiation of MAOI Therapy and Determination of Final Dosage

Typical starting dosages are 15 mg twice a day for phenelzine, 10 mg twice a
day for tranylcypromine, and 400 mg/day for moclobemide. Antidepressant
effects of selegiline tend to appear at 60 mg/day. Although it has been shown
in nongeriatric subjects that platelet MAO inhibition must reach 80% or
more to maximize response, in clinical practice this laboratory test is rarely
available, and maximum tolerable dosage or clear clinical response remains
the end point of dosage titration. Practically speaking, most elderly patients
experience dosage-limiting orthostatic hypotension at or before 60 mg/day of
phenelzine or 40 mg/day of tranylcypromine.
Management of MAOI Side Effects
Orthostatic hypotension may be managed via the approaches described earlier
in this chapter for cyclic antidepressants. Hypertensive crisis is usually signaled
by headache, flushing, diaphoresis, and palpitations and may progress to frank
hypertensive encephalopathy and neurological dysfunction. α-Adrenergic
blocking agents such as phentolamine (2–5 mg intravenously) or chlorpro-
mazine (50–100 mg intramuscularly) followed by smaller doses titrated
against blood pressure may be lifesaving. The common practice of giving pa-
tients a 50- or 100-mg tablet of chlorpromazine to carry with them for inges-
tion in an emergency has been criticized on the grounds that after ingestion,
many older patients may be so incapacitated as to be unable to reach the near-
est emergency department or may experience life-threatening loss of alertness
while driving for help.
Special Considerations Regarding MAOIs
A particular hazard is the use of sympathomimetic drug–containing cold tab-
lets and nasal sprays (e.g., ephedrine, pseudoephedrine, phenylephrine [Neo-
Synephrine], phenylpropanolamine), which may not be regarded as “real
medicine” by older patients. Patients must be most strenuously cautioned
against taking these medications. Meperidine, for reasons that are not yet
clear, interacts with MAOIs to produce an extremely serious syndrome of hy-
perpyrexia, muscular rigidity, and coma that has been fatal in several reported
instances. Other synthetic narcotics such as dextromethorphan also have been
implicated in causing this syndrome, which apparently does not occur with
natural narcotics such as morphine or codeine. For added safety, patients may
wear MedicAlert bracelets indicating that they are taking MAOIs and speci-
fying that they should not receive meperidine. Similarly, dental procedures
should be performed with local anesthetics that do not contain epinephrine.
Third-Line Agents—Psychostimulants
Although controlled studies in elderly patients are lacking, a relatively large
body of clinical literature supports the use of psychostimulants in elderly de-
pressed patients, particularly those in whom medical illness precludes the use
of cyclic antidepressants or MAOIs (Emptage and Semla 1996). Both am-
phetamines and methylphenidate have been administered, although meth-
ylphenidate is generally preferred because of its relatively lower cardiovascular
side-effect profile. Dosages range from 5 to 20 mg administered orally twice
a day, generally immediately before breakfast and lunch so as not to interfere
with appetite or sleep. Cardiovascular side effects are typically limited to very
minor increases in blood pressure and heart rate. The most common side ef-
fect is mild jitteriness, which may be managed with small doses of benzodiaz-
epine anxiolytics, but severe dysphoria and agitation, appetite disturbance,
and insomnia requiring discontinuation of treatment may occur rarely. One
retrospective comparison of methylphenidate and nortriptyline found that
both medications produced comparable rates of remission in patients with
poststroke depression but that the time to peak response for methylphenidate
was 2.4 days compared with 27 days for nortriptyline (Lazarus et al. 1994). A
double-blind, placebo-controlled study of poststroke depression found that
3 weeks of treatment with methylphenidate (in dosages up to 15 mg twice
daily) produced statistically significant but mild improvement in mood and
was well tolerated (Grade et al. 1998). Modafinil, a more recently developed
wake-promoting agent with psychostimulant properties, has been proposed
as an adjunct to antidepressant therapy, and results from several open-label
studies in nongeriatric subjects are encouraging (DeBattista et al. 2004; Ni-
nan et al. 2004).
Strategies for Antidepressant Treatment Resistance

Depressed patients whose symptoms have not responded to an adequate trial
of a single antidepressant are candidates for one or more alternative treatment
strategies: switching, augmenting, or combining antidepressants. For pur-
poses of this section, nonresponse means that significant residual symptoms

persist despite 6 weeks of treatment at adequate dosages of medication. Of
course, the meaning of “adequate dosage” depends on the medication used.
For nortriptyline, the dosage is adequate if it produces a plasma level between
80 and 120 ng/mL; for other TCAs and MAOIs, adequate means the highest
dosage tolerated; and for trazodone, bupropion, venlafaxine, mirtazapine,
and duloxetine, it means the full recommended adult dosage. For the SSRIs,
a small percentage of patients may become responders if the adult dosage is
doubled.
Switching to Another Antidepressant

The literature suggests that the preferred strategy is to switch from a single
neurotransmitter–reuptake blocker (e.g., an SSRI) to a combined serotonin
and norepinephrine–reuptake blocker (venlafaxine, duloxetine, or a TCA)—
or if the first agent is a combined reuptake blocker, to switch to a different
class of medication (i.e., TCA, MAOI, SSRI, or other reuptake inhibitor) that
is likely to be safely tolerated given the patient’s overall medical status
(Hirschfeld et al. 2002). The switch 1) from a TCA to an MAOI or venlafax-
ine or 2) from an MAOI to a TCA or venlafaxine also has been reported to
be effective in some cases. This literature generally focuses on nonelderly
adults, but in one study by Flint and Rifat (1996), the cumulative response
rate was 85% in 101 elderly patients receiving nortriptyline, which achieved
a 61% response rate; patients who did not respond to nortriptyline were then
switched to phenelzine, which achieved a 64% response rate.
Augmenting Ongoing Antidepressant Treatment

Augmentation involves adding to an ongoing antidepressant regimen a med-
ication that in amount or kind would not be expected to have antidepressant
effects. Medications used as augmenters include lithium, thyroid hormone
(levothyroxine or triiodothyronine), pindolol, methylphenidate, buspirone,
bupropion, risperidone, and olanzapine. Although no double-blind, placebo-
controlled, random-assignment studies of any of these approaches have been
done in elderly patients, the published database for lithium augmentation of
a cyclic antidepressant or an MAOI and thyroid hormone augmentation of a
TCA is most substantial and warrants review (Nelson 2000). The following
procedure for lithium augmentation is recommended: after an adequate trial
of cyclic antidepressant or MAOI, lithium is added in low doses (e.g., 300 mg

twice daily) and titrated to at least 0.4 mEq/mL. Rapid response (i.e., within
3–5 days) is common, but some patients require up to 2 weeks of augmenta-
tion before peak response occurs. Generally, side effects are additive. Thyroid
augmentation involves the addition of 25–50 µg/day of triiodothyronine to
an ongoing regimen of a TCA.
Combining Antidepressants
Combination therapy involves the simultaneous administration of two or
more agents in dosages that would be expected to have antidepressant effects
if administered alone. Combinations that appear, on the basis of largely un-
controlled, small studies, to be safe and to provide some enhanced effective-
ness over either agent administered alone include a TCA plus an MAOI, a
TCA plus an SSRI, an SSRI plus trazodone, an SSRI plus another SSRI,
moclobemide (a reversible MAOI) plus an SSRI, bupropion plus an SSRI,
bupropion plus venlafaxine, mirtazapine plus an SSRI, venlafaxine plus an
SSRI, and reboxetine plus an SSRI (Lam et al. 2002). Combinations chosen
to produce reuptake inhibition of both serotonin and norepinephrine may be
most effective. One double-blind, random-assignment study of middle-aged
adults with nonpsychotic major depression found that desipramine (norepi-
nephrine reuptake blocker) and fluoxetine (SSRI) together were significantly
more effective than either drug alone in inducing remission after 6 weeks of
treatment. Side effects (orthostatic hypotension, tachycardia) were those typ-
ical for desipramine (Nelson et al. 2004).
Which Strategy Is Best?

Because switching antidepressants requires tapering the first agent, then a
washout period, followed by administration of the second agent (with its own
latency of onset of action), and combination therapy exposes patients to at
least additive side effects and risks of adverse reactions, augmentation would
appear to be the optimal strategy for older patients with treatment-resistant
depression. Given the increased sensitivity of older patients to side effects and
adverse reactions, combination therapy must be regarded as the least advisable
of the three approaches to treatment resistance discussed in this section.
Maintenance Treatment
It is now well established that relapse and recurrence are best prevented by
maintaining patients on the same dose of antidepressant required to induce
remission. Reynolds (1994) used this approach with nortriptyline (titrating
blood levels between 80 and 120 ng/mL) and reported that 80% of remis-
sions were sustained for a year or more.
Psychopharmacotherapy for Psychotic

Depression
The proportion of depressed patients who present with delusions and/or hallu-
cinations appears to increase with age but does not seem to be related to age at
onset of depression (Brodaty et al. 1997). Treatment entails the simultaneous
administration of high-potency, low-dose antipsychotic medications such as
haloperidol, risperidone, or olanzapine in combination with a TCA, SSRI, or
other antidepressant. The Texas Medication Algorithm Project used this com-
bination successfully to treat psychotic depression in nonelderly adults. Their al-
gorithm specified that partial responders were switched from a TCA plus an
antipsychotic to a non-TCA plus an antipsychotic or from a non-TCA plus an
antipsychotic to a TCA plus an antipsychotic; patients who still did not respond
were switched to electroconvulsive therapy (ECT), and partial responders to
ECT were treated with a previously untried antidepressant with lithium aug-
mentation (Trivedi et al. 2004). The typical pattern of response is marked by
rapid (i.e., within days) reduction of anxiety, fear, social withdrawal, insomnia,
hypervigilance, and disordered behavior related to the delusional beliefs, fol-
lowed by gradual improvement (i.e., within a few weeks) in mood, neurovege-
tative symptoms, and hallucinations (if present), followed finally (i.e., within
weeks to months) by fading of the delusional beliefs per se. Remission rates are
usually much lower than is typical for nonpsychotic depression. Flint and Rifat
(1998a) reported a 50% response rate in elderly persons with psychotic depres-
sion who received treatment for 7 weeks with nortriptyline, perphenazine, and
lithium augmentation. Maintenance treatment requires full dosages of both
categories of medication because evidence indicates that the prognosis for suc-
cessful long-term remission is relatively poor when antidepressant monotherapy
is administered (Flint and Rifat 1998b).
Psychopharmacotherapy for Bipolar Depression

For patients with bipolar depression, treatment may be initiated with mood
stabilizers alone, and both lithium and lamotrigine have been shown to be ef-
fective antidepressants (Young et al. 2004). Dosing of lithium is as per guide-
lines in the section “Psychopharmacotherapy for Bipolar Disorder” later in
this chapter, and dosing of lamotrigine follows the same guidelines as for
young and middle-aged adults. If monotherapy is ineffective, antidepressants
may be added, following the principles spelled out earlier, with an important
modification. TCAs are the third-line treatment option in bipolar depression
because TCAs may be more prone to induce a switch into mania or hypoma-
nia than either 1) the SSRIs or other first-line agents (including venlafaxine,
duloxetine, and mirtazapine) or 2) MAOIs, the second-line treatment. Al-
though switch rates for elderly patients per se have not been published, Gijs-
man et al. (2004) reviewed six clinical trials in middle-aged adults and found
a 10% switch rate for TCAs and only 3.2% for all other antidepressants com-
bined (although the difference was not statistically significant). Antidepres-
sant treatment alone may be prescribed, but the most cautious approach calls
for simultaneous treatment with a mood stabilizer; in this context, lithium,
lamotrigine, valproate, and carbamazepine are all appropriate.
Electroconvulsive Therapy
ECT remains the single most effective treatment for major depression with or
without psychosis in elderly patients. Remission rates in the range of 75%–
90% or greater can be obtained in “naïve” patients (i.e., those who have not
tried and failed other treatments), but in the more typical elderly patient who
has had an inadequate response to other treatments, response rates (defined
as a decline of 50% or more in pretreatment depression ratings) are in the
80%–90% range, even in the “old-old” (i.e., older than 75), and side effects
are usually limited to transient memory impairment (Tew et al. 1999). ECT
is about equally effective in psychotic and nonpsychotic depression; however,
because psychopharmacological therapy has relatively limited effectiveness in
psychotic depression, this condition is the strongest indication for ECT as a
first-line therapy. Other indications for ECT as the treatment of first choice
include
• Active suicidality
• Severe anorexia
• High likelihood of inability to tolerate antidepressant side effects
• High likelihood of medication noncompliance
ECT is more commonly used, however, after psychopharmacological

treatment failure. Unilateral, nondominant electrode placement minimizes
memory impairment, but suprathreshold dosages of current (2.5 times sei-
zure threshold or more) are required to match the therapeutic efficacy of bi-
lateral treatment in elderly patients (Tew et al. 1999).
One effective approach is to use brief-pulse, bilateral electrode placement
at levels just above seizure threshold (typically between 60 and 140 millicou-
lombs), administering three treatments per week. The switch to high-dose
unilateral electrode placement is made only if memory impairment threatens
to endanger the patient or causes sufficient subjective distress to threaten con-
tinued compliance with treatment. Psychopharmacological treatments—
other than low-dose benzodiazepines, haloperidol, or an atypical antipsy-
chotic medication (e.g., risperidone, olanzapine, ziprasidone, quetiapine) as
needed for control of anxiety, sleep, agitation, or psychosis—are discontinued
during the course of ECT. Theophylline has been linked to status epilepticus
during ECT and also should be discontinued if possible (Fink and Sackeim
1998). Seizure generalization and duration are monitored via the cuff-isola-
tion technique, and stimuli producing a seizure that lasts for less than 25 sec-
onds are repeated.
Treatments are administered until symptom reduction has reached a pla-
teau, defined retrospectively as “no further improvement over the past three
treatments.” This approach is more aggressive than that used by either the
typical community-based program or most clinical trials. A naturalistic study
of ECT as administered in the community found that outcomes were signif-
icantly worse (i.e., remission achieved in only 30%–47%) than those reported
in clinical trials, and the investigators concluded that the most likely explana-
tion for the unexpectedly low remission rate was that community practition-
ers often discontinued treatment before full remission was reached (Prudic et
al. 2004). Our approach produces outcomes similar to (or better than) those
achieved in clinical trials and typically requires about 9 treatments to produce
full remission (although the range can be from 6 to 20). Our approach also
seems to produce a more enduring response, at least in the first several weeks
after treatment, than that reported by most investigators. Prophylactic anti-
depressant treatment is initiated immediately after the last ECT treatment.
The associated anterograde memory impairment, which is cumulative
over the course of treatment, typically reaches the level of mild disorientation
to time and mild to moderate anterograde and retrograde memory loss. All of
these symptoms usually clear rapidly and are clinically undetectable a week or
so after the last treatment, but in some cases, they may persist for as long as 3
or 4 weeks. Retrograde memory loss, especially for events occurring during
the course of treatment, may persist much longer, and memory for some in-
trahospitalization events may be permanently lost. Given this information,
along with the recovery statistics mentioned earlier, and the extremely low
mortality rate of ECT (less than 1 death per 10,000 patients), the great ma-
jority of patients are willing to accept this degree of memory loss as part of the
cost of treatment.
Experimental Therapies
Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) uses a rapidly changing
magnetic field (produced by electrical coils placed near the scalp) to induce
electrical current in brain tissue. It has been studied as an adjunct to antide-
pressants and as a solo treatment for depressive disorders and is regarded by
some investigators as a potential alternative to ECT. Results from open stud-
ies have been mixed, and a meta-analysis by Martin et al. (2003) concluded
that “current trials are of low quality and provide insufficient evidence to sup-
port the use of rTMS in the treatment of depression” (p. 480). Studies pub-
lished since that review offer little to challenge that assessment. A double-
blind, controlled study found “a modest, clinically nonrelevant decrease in
HAM-D scores in both rTMS and sham patients over 2 weeks of treatment”
(p. 1323), but over the subsequent 12-week follow-up, the rTMS group con-
tinued to improve significantly compared with the placebo group. The au-
thors concluded that “decrease of depressive symptoms may continue after
the cessation of rTMS stimulation” (Koerselman et al. 2004, p. 1323). An
open study supported this conclusion, finding persistent antidepressant ef-

fects of rTMS over a 4-month follow-up period (Benadhira et al. 2005).
Vagus Nerve Stimulation

Brain stimulation via application of pulsed electrical current to the left cervi-
cal vagus nerve has established efficacy as adjunctive therapy in treatment-
resistant epilepsy and also has been studied in treatment-resistant depression.
The procedure requires surgical implantation of a device that applies small
doses (typically less than 1.5 mA) of electrical current to the vagus nerve mul-
tiple times per second (a typical frequency is 20 Hz) for varying periods, with
a typical schedule being 30 seconds every 5 minutes. The dose is externally
controllable and is typically set to cycle continuously, 24 hours per day. Side
effects are usually minimal and include voice alteration, neck pain, and dys-
pnea. Psychotropic medications are commonly administered concomitantly,
and even ECT has been administered to patients with an implanted stimula-
tor, although the device was turned off during ECT (Marangell et al. 2002).
Results of several small, open studies have been promising: Rush et al.
(2000) reported 40% improvement in 30 patients receiving treatment for 10
weeks, and a 1-year follow-up study of the same subjects (Marangell et al.
2002) found that the response rate was sustained and that the remission rate
actually increased (from 17% [5 of 30] to 29% [8 of 28]). On the basis of
these and other results, a large-scale, multicenter, double-blind, randomized,
parallel-group, sham-controlled study is under way at 21 academic sites in
North America. Preliminary results from a subset of 21 subjects (11 who re-
ceived active treatment for 22 weeks and 10 who received active treatment for
10 weeks and sham treatment for 12 weeks) in this study indicated no statis-
tically significant difference in outcome, as measured by Ham-D and Clinical
Global Impression Scale scores, but there was a trend toward greater reduc-
tion in Ham-D scores in the subjects who received 22 weeks of active treat-
ment (Carpenter et al. 2004). None of the studies of vagus nerve stimulation
has focused on elderly patients, and a more definitive conclusion regarding
the role of vagus nerve stimulation in geriatric depression must await the re-
sults of the larger study.
Complementary and Alternative Approaches

According to a recent national survey, 50% or more of patients who report
severe depression have used complementary and alternative therapies in an
attempt to alleviate symptoms (Kessler et al. 2001). These approaches in-
clude cognitive techniques such as relaxation and biofeedback, oral medica-
tions such as herbal medicine and homeopathy, physical treatments such as
massage and chiropractic, and other approaches such as spiritual healing and
dietary modification. Most persons using these approaches also seek treat-
ment professionally (e.g., by a psychiatrist, psychologist, or general physi-
cian), which provides an opportunity to assess for possible adverse effects of
combining alternative therapies with pharmacotherapies (e.g., mild seroto-
nin syndrome from mixing St. John’s wort and SSRIs). Clinicians need to in-
quire about the use of complementary and alternative approaches, become
familiar with current data on efficacy, and inform patients of any potential
known risks. A recent meta-analysis on adverse effects of St. John’s wort con-
cluded that it is safe and well tolerated if taken under control of a physician
(Knuppel and Linde 2004), but use of this supplement appears to have de-
clined among adults in the United States from a peak in the 1990s (Kelly et
al. 2005).
Encouraging lifestyle modifications such as regular exercise may be useful
in reducing depressive symptoms, especially in combination with other ther-
apies. Group therapy that used an eclectic approach that combined exercise
and preventive health behaviors with psychotherapies (including cognitive
and reminiscence therapies) and social skills training was effective in reducing
depressive symptoms among a large group of older women living in subsi-
dized housing; however, it was more effective among relatively young (55- to
75-year-old) white women than among minority women and individuals
older than 75 (Husaini et al. 2004).
Educational materials that explain geriatric depression and its effect on
family systems (e.g., Miller and Reynolds 2003) are a potentially beneficial
adjunct to family, group, or individual therapy. However, few controlled stud-
ies of the effectiveness of such self-help materials in treating depression have
been done. A recent meta-analytic review (Anderson et al. 2005) not limited
to studies of geriatric patients found beneficial effects compared with a de-
layed-treatment control condition for bibliotherapies that use the popular
book Feeling Good (Burns 1999); however, many other self-help depression
books on the market have not been systematically studied.
Hypomania and Mania

The treatment of signs and symptoms of elevated mood (including reduced
need for sleep, irritability, distractibility, hyperactivity, pressured speech,
flight of ideas, circumstantiality and tangentiality, grandiosity, impulsivity,
and excessive involvement in pleasurable activities that have a high potential
for painful consequences), with or without hallucinations and delusions, in
elderly patients generally follows the same principles as for young and middle-
aged adults. In hypomania or mania due to a general medical condition, the
underlying medical condition is typically treated in parallel with psychosocial
and psychopharmacological management of signs and symptoms of hypoma-
nia. Similarly, substance-induced hypomania or mania is treated by discon-
tinuing or adjusting the dosage of offending substances, when possible.
Although this discontinuation or adjustment may be adequate to bring signs
and symptoms under control, safety considerations may warrant initiating
psychosocial and psychopharmacological management of signs and symp-
toms while waiting for the substance effects to wear off and euthymia to re-
turn.
Bipolar Disorder
The site of treatment of bipolar disorder depends on the urgency of the clin-
ical situation. In the acute manic phase, inpatient treatment is indicated,
whereas outpatient management is often sufficient for hypomania or bipolar
depression without suicidality.
Psychosocial Therapy for Bipolar Disorder

Psychosocial treatment of mania and hypomania is typically aimed at opti-
mizing compliance with somatic therapies and assisting patients and families
with the often daunting task of establishing and maintaining appropriate be-
havioral boundaries. Counseling and support are also useful in the aftermath
of a hypomanic or manic episode, when patients may find themselves alien-
ated from friends, family, treating physicians, and other caregivers. Generally,
insight-oriented therapies are avoided during the acute phase of illness but
may be quite effective when the most severe symptoms are under control.
Both individual and family therapy approaches can be used, whereas group
settings may not provide enough structure to allow the elderly bipolar patient
to benefit. Psychosocial treatment of bipolar depression is similar to the treat-
ment of unipolar depression but calls for more psychoeducation of the patient
and family regarding the early signs of a switch into mania, which can occur
spontaneously or be provoked by antidepressant therapy.
Psychopharmacotherapy for Bipolar Disorder

Depending on the acuity of illness, psychopharmacological management of
hypomania or mania in elderly patients may occur in an inpatient or an out-
patient setting. Inpatients are typically more impaired and may require a two-
phase approach to treatment. In phase one, the most dangerous or crippling
symptoms are rapidly brought under control, and in phase two, remission is
sought.
Phase One—Acute Stabilization and Phase Two—Acute Treatment

A widely used approach to phase one entails administration of high-potency,
low-dose neuroleptic medications such as oral or intramuscular haloperidol,
olanzapine, or ziprasidone, or comparable oral doses of risperidone. Initial
doses are in the range of 0.5–2.0 mg for each and are gradually raised until
side effects supervene or symptoms are controlled. Typical effective dosages
are 1–2 mg/day of haloperidol, 1–4 mg/day of risperidone, 5–10 mg/day of
olanzapine, and 10–20 mg/day of ziprasidone (which is contraindicated in
patients who have a prolonged QTc interval, recent myocardial infarction, or
uncompensated congestive heart failure or who are taking other medications
that can prolong the QTc interval).
Once symptoms are controlled, phase two entails oral administration of
lithium carbonate, divalproex, or another mood-stabilizing agent. If lithium
is selected, the appropriate pretreatment evaluation is conducted (see subsec-
tion “Pretreatment Evaluation—Lithium Therapy” later in this chapter), and
then dosages are adjusted to achieve serum levels in the 0.4–0.8 mEq/mL
range. It is important to remember that elderly patients typically have reduced
glomerular filtration rates (by 30%–50%) compared with young adults, and
the elimination half-life of lithium may be increased up to 36 hours. There-
fore, elderly patients generally require smaller dosages of lithium to reach
therapeutic serum levels; a typical starting dosage may be as low as 150 mg/
day. The increased half-life allows once-a-day dosing, which is also believed
to reduce side effects compared with divided doses (Hardy et al. 1987). After
6–7 days at a steady daily dosage, serum for determination of lithium level is
drawn, and an approximately linear dose–serum level relation is assumed
within therapeutic dosage ranges.
Divalproex is an acceptable alternative to lithium in manic elderly pa-
tients, particularly in those who develop deterioration of cognitive perfor-
mance during lithium treatment (Young et al. 2004). Dosages of divalproex
range from 400 to 1,000 mg/day (in divided doses) and are adjusted to pro-
duce serum levels between 50 and 120 µg/mL. Divalproex may be of partic-
ular value in rapid-cycling patients and those with mixed mania (i.e., with
depressive symptoms and manic symptoms). Side effects are usually minimal
and include sedation, nausea, and ataxia.
Other agents that have been proposed for acute and maintenance treat-
ment of geriatric bipolar disorder include the anticonvulsants carbamazepine,
oxcarbazepine, lamotrigine, topiramate, and gabapentin, but none has been
studied in elderly bipolar patients per se. Studies in middle-aged subjects sug-
gest that carbamazepine and lamotrigine both have acute (i.e., phase two)
antimanic effects and also may be effective for prophylaxis of mania and hy-
pomania (Ichim et al. 2000; Sachs et al. 2000).
Carbamazepine may be most effective in manic patients who cycle rapidly
and who have predominantly irritable rather than euphoric mood, features that
have been reported to occur relatively commonly in elderly manic patients.
Dosages of carbamazepine (typically beginning at 200 mg orally twice a day) are
adjusted to produce blood levels in the range of 4–12 ng/mL, and antimanic
effects appear after 4–7 days. Because carbamazepine induces its own metab-
olism, dosage increase is commonly required after 4–6 weeks of therapy to
maintain therapeutic blood levels. Side effects of and adverse reactions to car-
bamazepine include sedation, dizziness, ataxia, nausea and vomiting, mild an-
ticholinergic effects, skin rash (rarely including Stevens-Johnson syndrome and
toxic epidermal necrolysis), and worsening of congestive heart failure, hyperten-
sion, and hypotension. Rare cases of aplastic anemia and agranulocytosis also
have been reported; thus, baseline blood studies and periodic reevaluations are
necessary for patients taking this drug. Carbamazepine undergoes hepatic mi-
crosomal metabolism, so the general pharmacokinetic and pharmacodynamic
considerations discussed in Chapter 2 (“Normal Aging”) apply.
Lamotrigine in nonelderly manic patients is as effective as lithium for
phase two management, and one study in elderly patients found that lamo-
trigine added to lithium or divalproex led to remission (Robillard and Conn
2002). To reduce the risk of rash, a rigid schedule of dosage increases is re-
quired: for nonelderly adults, it is 25 mg once daily for 1 week, 50 mg once
daily for the second week, and 100 mg once daily for the last 2 weeks. Elderly
patients may require even smaller dosages at each step.
Phase Three—Long-Term Management of Bipolar Disorder

Once remission of mania, hypomania, or bipolar depression is achieved, the
next goal of treatment is long-term prevention of recurrence. As is the case for
young adults, divalproex, carbamazepine, other anticonvulsants, and lithium
are the primary agents in widespread use. Plasma levels of lithium in the elderly
are generally lower than those required for reduction of acute symptoms, typ-
ically in the range of 0.3–0.8 mEq/mL. Dosages required to sustain these levels
are typically lower than those needed for middle-aged adults, and elderly pa-
tients are somewhat more prone to develop toxicity at any given plasma level
of lithium; otherwise, principles of management are essentially the same as for
younger patients. Divalproex and carbamazepine are also effective for long-
term management, and dosages are adjusted to minimize side effects while
maintaining blood levels in the therapeutic range described earlier.
Pretreatment Evaluation—Lithium Therapy

Physical and neurological examination, laboratory studies, and a 12-lead elec-
trocardiogram are recommended. The physical and neurological examination
should be specifically oriented toward detecting thyroid enlargement, evi-
dence of renal dysfunction, and tremor, all of which may be exacerbated by
lithium therapy. Evidence of congestive heart failure, which may require ini-
tiation of diuretic therapy, is particularly important because diuretics can sig-
nificantly increase lithium blood levels. In patients with musculoskeletal
disease who may require treatment with nonsteroidal anti-inflammatory
agents or patients with hypertension who may require angiotensin-converting
enzyme inhibitors, caution is necessary because both categories of medication

can cause clinically significant increases in serum lithium levels. The electro-
cardiogram is aimed at ruling out sick sinus syndrome, which is a strong rel-
ative contraindication to lithium therapy because significant bradycardia or
dysrhythmia may be precipitated. Benign nonspecific T-wave abnormalities
and U waves that reverse with cessation of treatment are common in patients
taking lithium and do not require discontinuation of treatment. The labora-
tory evaluation is oriented toward detection of renal dysfunction (i.e., serum
creatinine, serum urea nitrogen, electrolytes) and establishment of pretreat-
ment thyroid function (thyrotropin, total triiodothyronine). Because lithium
therapy can affect thyroid function, periodic (e.g., every 6 months) physical
examination of the thyroid and reevaluation of serum thyrotropin and tri-
iodothyronine levels are recommended.
Management of Lithium Side Effects
Acute side effects include nausea, diarrhea, mild polydipsia and polyuria, and
generalized fine tremor. Nausea can be minimized by administering doses af-
ter meals and by preceding doses with prophylactic antacids. Diarrhea is usu-
ally mild and intermittent and rarely requires concomitant antidiarrheal
therapy. Tremor is not usually of clinical significance and rarely requires dos-
age manipulation. Delirium, sedation, and “cognitive dulling” can occur but
are typically seen at higher serum levels (i.e., >1.0 mEq/mL). Side effects of
long-term lithium therapy may include hypothyroidism and goiter, and the
question of renal tubular damage remains controversial.
Pretreatment Evaluation—Other Mood Stabilizers

Divalproex can cause thrombocytopenia, and carbamazepine can cause neutro-
penia, hepatic toxicity, and, rarely, agranulocytosis. A complete blood count is
recommended prior to initiating treatment with either agent, and liver function
studies should be done prior to initiating carbamazepine therapy.
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5
Dementia and
Alzheimer’s Disease
Identifying the Dementia Syndrome
History
An accurate history of the current illness is particularly important in the di-
agnostic evaluation of dementia, in order to 1) establish the temporal rela-
tionship between possible etiological factors and the onset of cognitive
decline, which can help to identify the underlying pathophysiological process
causing dementia; and 2) permit the potentially important distinction be-
tween early- and late-onset Alzheimer’s disease. Accordingly, multiple sources
of information, including the patient’s medical records, should be used to
supplement information provided by the patient and the patient’s primary
caregiver, and an attempt should be made to establish detailed timelines. It is
particularly important to focus on trauma; signs or symptoms of neurological
or psychiatric illness; substance use, including alcohol and medications; past
and present exposure to potential toxins; past surgeries; and past and present
psychosocial stressors. The family history should include inquiry about
Down syndrome, dementia, and neurological or mental illness.
Mental Status Examination

A comprehensive clinical mental status examination remains the cornerstone
of the diagnosis of dementia. General categories of appearance; level of alert-
ness; degree of cooperation; mood; affect (direction and degree); form, flow,
173
and content of thought; psychomotor activity; presence or absence of hallu-

cinations, delusions, and other morbid thought content; and judgment and
insight are assessed along with cognitive function.
Clinical assessment of mental status may be supplemented by adminis-
tration of a structured examination of the type described in the next section.
Results of these procedures can provide a valuable baseline for assessing treat-
ment-related cognitive changes and also can be used to determine whether a
referral for neuropsychological assessment is desirable or feasible.
Standardized Measures for Rating Cognition

The choice of a cognitive screening tool should be based on several consider-
ations. The selected screen should tap the core cognitive processes of the dis-
orders most commonly represented in the practice setting, should have
acceptably high diagnostic accuracy, and should meet the practical needs of
the situation (e.g., available time and personnel). All cognitive screens per-
form better in practice settings where dementia is commonly observed and
less well in community-based settings or primary care, where the base rate of
serious cognitive problems is lower. As a result, it is generally not appropriate
to extrapolate from initial studies of new instruments that rely on well-char-
acterized, clinically distinct samples of dementia patients and control subjects
in estimating how the instrument will perform in a more heterogeneous prac-
tice setting. As additional validation studies accumulate for a particular in-
strument, it becomes easier to determine whether a particular screening scale
is right for a given situation.
Table 5–1 lists several cognitive mental status examinations appropriate
for geriatric patients, and the Appendix provides test forms or additional in-
formation on several of these scales. Some tests, such as Animal Naming, the
Mini-Cog, and the short form of the Orientation-Memory-Concentration
Test, are very brief and are intended only for gross screening. The Mini-Men-
tal State Examination (MMSE; Folstein et al. 1975), the Cognitive Abilities
Screening Instrument (CASI; Teng et al. 1994), and the Neurobehavioral
Cognitive Status Examination (Kiernan et al. 1987) are of intermediate
length and may be useful in a wide range of psychiatric and medical settings.
The Dementia Rating Scale (DRS; Mattis 1976), now available in an updated
form (DRS-2; Jurica et al. 2001), is the most comprehensive of the mental
status instruments developed for older adults. Items are hierarchically ar-
Table 5–1. Cognitive mental status examinations and brief screening tools
Administration Advantages and
Measure Description time (min) applications Limitations
Mini-Mental State 11-item, 30-point scale 5–10 Brief; examines several Insensitive to mild or focal
Examination (MMSE; assesses orientation, functions; wide deficit; high false-
Folstein et al. 1975) registration and delayed application; good norms positive rate with poorly
recall, language, educated patients
attention,
visuoconstruction
Cognitive Abilities 20 items from modified 10–15 100-point scoring range May not be more sensitive
Dementia and Alzheimer’s Disease

Screening Instrument form of the MMSE and may make it sensitive to to dementia than the
(CASI; Teng et al. 1994) Hasegawa Dementia mild impairment; standard MMSE for
Screening Scale, plus different versions most populations
judgment question developed in different
locales and languages
Cognistat Separate scales assess 20–30 Profile format assists in Limited data on validity of
(Neurobehavioral attention, orientation, giving feedback; screen separate scales or
Cognitive Status language, memory, and metric allow quick applicability to diverse
Examination [NCSE]; visuoconstruction, testing of intact persons samples
Kiernan et al. 1987) calculation, reasoning
175
Table 5–1. Cognitive mental status examinations and brief screening tools (continued)

Dementia Rating Scale Scales assess attention, 30–45 May detect subcortical or Take too much time to
(DRS; Mattis 1976) conceptualization, frontal brain deficit; administer in some
DRS-2 (Jurica et al. 2001) memory, initiation and sensitive to wider range of situations; limited data
perseveration, dementia than are briefer on use with diverse
visuoconstruction scales samples
Animal Naming task Naming animals as quickly 1 Extremely brief; will detect Insensitive to mild deficit
(e.g., Duff Canning et al. as possible for 60 seconds moderate to severe or conditions affecting
2004) dementia; may be useful nonlanguage skills;
as an initial screen when cutoff scores likely to
time is very limited vary by education level
and ethnicity
Clock Drawing Test Drawing the face of a clock 2–5 Very brief; well accepted by Insensitive to mild deficit;
(e.g., Shulman 2000) and setting hands to a patients; sensitive to no generally accepted
specified time parietal function and method of
some aspects of frontal or administration and
executive function; will scoring; does not assess
detect moderate to severe memory processes most
dementia directly affected by
Alzheimer’s disease
Table 5–1. Cognitive mental status examinations and brief screening tools (continued)
Mini-Cog Three-word learning and 2–4 Very brief; will detect Insensitive to mild deficit;
(Borson et al. 2000) recall task plus clock moderate to severe relatively new test, and
drawing dementia; developed for independent validation
use with ethnically and studies are needed
linguistically diverse
populations
Orientation-Memory- Six items assess temporal 3–5 Very brief; will detect Insensitive to mild deficit

Concentration Test orientation, recall of an moderate to severe and visuospatial
(OMCT; Katzman et address, mental control dementia impairment
al. 1983)
Memory Impairment Free and cued recall of four 3–5 Very brief; designed to tap Limited data available on
Screen (MIS; Buschke et words memory processes most applicability to diverse
al. 1999) impaired in early samples; assesses only
dementia one cognitive domain
177
ranged within sections, so that the first item serves as a screen for intact ability
in each domain. This scale provides more extensive assessment of language,
memory, and praxis than do most mental status examinations and includes
items that may be sensitive to frontal-lobe impairment (initiation and perse-
veration sections). The DRS is recommended for use in patients who have
mild impairment when a detailed assessment of abilities is desired and when
time permits complete administration.
A Closer Look at the MMSE
Table 5–2 presents sample items from the popular MMSE. The widespread use
of this test with diverse populations is likely to ensure its continued popularity,
despite some recognized limitations. The MMSE, initially validated with el-
derly psychiatric groups and nonpsychiatric community control subjects, has
been translated into several languages, and a modified form suitable for hearing-
impaired patients is also available. The MMSE has high interrater reliability
and adequate retest reliability in stable conditions. Folstein and colleagues
(1975) have emphasized that the MMSE does not establish a diagnosis of de-
mentia; instead, as with all screening instruments, it identifies individuals with
possible cognitive impairment that may warrant further assessment.
Initially, a score of 23 or fewer correct items was recommended as a cutoff
to screen for cognitive impairment. However, subsequent studies have shown
that this cutoff score is likely to overidentify poorly educated persons as im-
paired and fail to detect true decline in well-educated individuals. Table 5–3
presents median values and scores at the twenty-fifth percentile for several age
and educational groups, based on an epidemiological survey of more than
18,000 persons from several areas within the United States. Scores at the
twenty-fifth percentile are above typical cutoffs for impairment, but if the his-
tory or other observations raise a question of decline, a score at this level may
warrant further assessment or monitoring. It is obvious from the values shown
in the table that both age and education influence MMSE scores and that a
specific score for a particular individual must be interpreted in light of these
characteristics and other historical and medical information.
Although the MMSE was not specifically designed to screen for Alzheimer’s
disease, certain items—most notably, delayed recall and copying of penta-
gons—are likely to be failed by patients with Alzheimer’s disease. Recalling of
only two of three words, or even one word, may fall within normal limits for
Dementia and Alzheimer’s Disease 179
Table 5–2. Sample items from the Mini-Mental State Examination

(MMSE)
Cognitive skill Task(s) Score
Orientation for timea “What is the date?” 0–1

Registration “Listen carefully, I am going to say three words. 0–3
You say them back after I stop. Ready? Here they
are… HOUSE (pause), CAR (pause), LAKE
(pause). Now repeat those words back to me.”
(Repeat up to five times, but score only the first
trial.)
Naming “What is this?” (Point to a pencil or pen.) 0–1
Written command “Please read this and do what it says.” (Show 0–1
examinee the words on the stimulus form:
CLOSE YOUR EYES.)
aComponent
of the MMSE that is particularly sensitive to mild Alzheimer’s disease (Galasko et
al. 1990; Teng et al. 1987).
Source. Reproduced by special permission of the Publisher, Psychological Assessment Re-
sources, Inc., 16204 North Florida Avenue, Lutz, FL 33549, from the Mini Mental State Exam-
ination, by Marshal Folstein and Susan Folstein, Copyright 1975, 1998 by Mini Mental LLC,
Inc. Published 2001 by Psychological Assessment Resources, Inc. Further reproduction is pro-
hibited without permission of PAR, Inc. The MMSE can be purchased from PAR, Inc., by call-
ing (813) 968–3003.
some older persons, but inability to recall any words, particularly when prompts
are provided, strongly suggests a problem with retention characteristic of
Alzheimer’s disease or other disorders producing amnesia. Many patients with
Alzheimer’s disease will have forgotten that they were asked to remember some
words when delayed recall is requested. Other items on the MMSE that are sen-
sitive to early or mild Alzheimer’s disease are design copying and temporal ori-
entation. This scale is not sensitive to executive or psychomotor changes, and as
a result, it is less useful in screening for frontotemporal dementia or subcortical
dementia (see Chapter 6, “Other Dementias and Delirium”).
Despite careful attempts at translation, research suggests that some
MMSE items may be biased for use with populations whose primary lan-
guage is not English or whose cultural identification differs from that of
normative samples, which are largely white and middle class. Several items
showed significant ethnicity or language differences in a comparison of white
Table 5–3. Mini-Mental State Examination scores by age and educational level

Age (years)
Education 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
0–4 years
Median 22 22 22 22 21 21 19 20
25th percentile 20 20 19 19 19 18 16 15
5–8 years
Median 27 27 27 27 26 26 25 24
25th percentile 25 25 24 24 24 22 22 21
9–12 years
Median 29 29 28 28 28 27 26 26
25th percentile 27 27 27 27 26 25 23 23
Some college or higher
Median 30 29 29 29 29 28 28 28
25th percentile 28 28 28 28 27 27 26 25
Source. Adapted from Crum RM, Anthony JC, Bassett SS, et al.: “Population-Based Norms for the Mini-Mental State Examination by Age and Ed-
ucational Level.” Journal of the American Medical Association 269:2386–2391, 1993. Copyright © 1993, American Medical Association. All rights re-
served.
and Hispanic adults, and another study found that the MMSE misclassified
more nonimpaired Hispanic elderly persons as cognitively impaired than did
a memory test based on learning and recall of 10 common objects (Loewen-
stein et al. 1995). However, some of the items most sensitive to Alzheimer’s
disease (delayed recall and design copying) are minimally affected by ethnicity
and educational differences. The CASI (Teng et al. 1994) (see Table 5–1) in-
cludes items from the MMSE and the Hasegawa Dementia Scale (Tsai and
Gao 1989) that have been modified to accommodate translation problems
and differential difficulty across various countries as suggested by pilot test-
ing. Developed initially for patients in Japan and the United States, this test
has now been used in several large-scale studies that provide normative refer-
ence points (e.g., McCurry et al. 1999). Performance on the CASI, like the
MMSE, is influenced by age and education in older adults without dementia.
Abbreviated Cognitive Screens
There has been an emphasis in recent research on the development and vali-
dation of very brief cognitive assessment tools that might be suitable for de-
mentia screening in primary care settings or other situations when time is very
limited (Lorentz et al. 2002).
Category fluency measures, especially Animal Naming, have long been
included in neuropsychological testing batteries to evaluate retrieval from se-
mantic memory, and recent studies examining the diagnostic accuracy of such
tasks suggest that they could play a role as brief, initial screens for dementia
of several types. In two independent cohorts of older adults being followed up
for dementia, a 60-second Animal Naming task performed as well in detect-
ing Alzheimer’s disease as did the MMSE, and when the Animal Naming task
was combined with recall of a five-item name and address (“John Brown 42
Market Street Chicago”), sensitivity and specificity surpassed those of the
MMSE (Kilada et al. 2005). Another study (Duff Canning et al. 2004) that
examined well-diagnosed cases of Alzheimer’s disease and vascular dementia
found the Animal Naming task to be the best of several verbal fluency tasks
in differentiating patient groups from control subjects; sensitivity to dementia
was high, even among persons with MMSE scores greater than 24. In that
study, which mainly included well-educated older adults, a cutoff score of less
than 14 animals in 60 seconds was highly effective in detecting dementia.
However, optimal verbal fluency cutoff scores are likely to vary by education
level and, possibly, ethnic and linguistic background, and care must be taken
to use appropriate normative reference points. Animal Naming is not recom-
mended as a stand-alone cognitive screen, but it may be useful as part of a
multistep screening procedure in which persons with low fluency scores are
then given additional screens or tests.
Clock drawing tests also have been widely used for very brief cognitive
screening. Attempting to re-create such a familiar item is generally acceptable
to patients, and the visual outcomes can be useful in showing undetected cog-
nitive problems to patients or their family members. Administration time varies
depending on the version used and the patient’s psychomotor skills, but many
patients can complete the task in 1 or 2 minutes. A recent review of clock draw-
ing procedures for dementia screening (Shulman 2000) found fairly high sensi-
tivities and specificities (about 85%), and outcomes usually were not affected
by linguistic background. However, very old persons, or those with little or no
education, are likely to perform less well. A practical drawback to clock drawing
is the lack of standard procedures for administration and scoring. Some meth-
ods require the patient to draw the circle for the clock face, whereas others
present a predrawn circle. Scoring ranges from a simple pass-or-fail method to
relatively elaborate systems of 20 or more points (see Appendix for references to
scoring systems). Another limitation is that clock drawing does not directly test
for impaired memory, which is the core early deficit in Alzheimer’s disease and
certain other dementias. Because of these drawbacks, the Clock Drawing Test
is generally not used as a stand-alone screening measure.
The Mini-Cog (Borson et al. 2000) is composed of a three-item word
learning and recall task and a simple clock drawing task. By combining the
most sensitive item used in the MMSE and CASI (i.e., word-list recall) with
a visual task that can detect parietal dysfunction and some aspects of frontal
and executive deficits, the Mini-Cog has been shown to perform as well as or
slightly better than the full MMSE in identifying probable Alzheimer’s disease
and some other dementias. Administration time runs from 2 to 4 minutes,
and scoring is relatively simple and straightforward. An additional advantage
is that this test was designed for and has been validated with multiethnic el-
derly populations (black, Asian American, and Hispanic) and appears less
likely to be biased by low education and literacy than is the full MMSE (Bor-
son et al. 2005). A recent review of the performance of cognitive screening
tests in diverse groups (Parker and Philp 2004) concluded that, in general,
short tests yield more consistent data across varying cultures and education
levels and may be better accepted by patients compared with lengthier and
more demanding measures.
The Orientation-Memory-Concentration Test (OMCT), a six-item ver-
sion of the Blessed Information Memory Concentration Test (Katzman et al.
1983), takes approximately 5 minutes to administer. It taps several skills often
affected in dementias of various types, including temporal orientation, men-
tal control (counting backward and reciting months backward), and memory
for verbal narrative (a spoken phrase). The OMCT correlates highly with the
MMSE, but in at least one study, it was found to be more sensitive to mild or
subclinical dementia (Brooke and Bullock 1999). Advanced age and very low
education adversely affect scores.
The Memory Impairment Screen (Buschke et al. 1999) looks in a brief but
well-designed way at a single skill: the ability to learn and retrieve new informa-
tion. The patient is shown four large-print words on a page and is asked to read
each word and then point to and name each word again in response to a cate-
gory cue (e.g., the cue word for “apple” would be “fruit”). After a delay of about
2 minutes filled with an unrelated task (counting forward and backward from
1 to 20), both free and cued recall are assessed. Administration time is about
4 minutes, and the total score combines both free and cued recall. For popula-
tions with different base rates of disease, the authors provide recommended cut-
off scores for use in screening for dementia and for Alzheimer’s disease.
Preliminary data from a small number of patients suggested that the Memory
Impairment Screen may be more sensitive to mild dementia than are most other
screens. The Memory Impairment Screen is more effective in identifying
Alzheimer’s disease than is the three-word recall task from the MMSE (Kuslan-
sky et al. 2002), has been adapted for telephone screening, and has been trans-
lated into Spanish. Although the Memory Impairment Screen is a promising
screening tool, it has not been used widely yet, and the relative lack of indepen-
dent validation data is a limitation.
Rating Functional Skills

Although testing of cognitive function is useful in the detection and diagnosis
of dementia, most treatment and management decisions revolve around the pa-
tient’s functional abilities. Ability to perform everyday activities in an indepen-
dent fashion is only modestly correlated with outcomes of mental status
examinations or neuropsychological tests, and thus it is important to assess

these skills in addition to testing mental status when dementia or other cogni-
tive impairments are suspected. Also, because persons with little or no educa-
tion often perform poorly on mental status examinations, a very brief mental
status examination, combined with functional assessment, may be preferable to
more extensive cognitive assessment for screening or diagnosing dementia
(Wilder et al. 1995). Several brief rating scales have been developed for use with
family members or other caregivers to identify problems in everyday function-
ing. A widely used functional scale is the Instrumental Activities of Daily Living
measure developed by Lawton and Brody (1969) (see Appendix), which con-
sists of eight items assessing areas of function considered crucial for maintaining
independent living in the community (e.g., using the telephone, shopping, be-
ing responsible for medications). The Direct Assessment of Functioning Scale
(Loewenstein et al. 1989) presents tasks to the patient—such as making change,
addressing an envelope, or telling time—instead of relying on informants’ re-
ports of everyday function. Developed for use with elderly persons with mild to
moderate dementia, this scale yields generally comparable outcomes for both
English- and Spanish-speaking patients.
Other Rating Measures

Other observer-rated scales have been developed to aid in screening for de-
mentia or to identify specific psychiatric symptoms that can accompany de-
mentia. Examples of such scales include the Informant Questionnaire on
Cognitive Decline in the Elderly (IQCODE; Jorm et al. 1991) and the Neu-
ropsychiatric Inventory (NPI; Cummings 1997). The IQCODE relies on
observations of caregivers or others familiar with everyday behaviors and
abilities of the patient. The scale measures a single general factor of cogni-
tion, has high reliability, and performs as well as brief cognitive screening
tests in detection of dementia (Jorm 2004). Unlike scores on many cognitive
screening tests, scores on the IQCODE are relatively unaffected by educa-
tion, premorbid ability levels, or language proficiency. The NPI (Cummings
et al. 1994) is rated by physicians or trained professionals on the basis of ob-
servation of the patient and input from caregivers. The NPI provides fre-
quency and severity ratings for 12 psychiatric and behavior problems
commonly observed in dementia, including agitation, delusions and hallu-
cinations, and apathy and indifference (see Appendix for NPI items). It has
been translated into several languages for use in cross-cultural investigations

and has acceptable validity and reliability (Cummings 1997). A modified
version for use in nursing homes is also available.
Laboratory Evaluation
Laboratory evaluation is aimed at identifying illnesses known to cause de-
mentia and generally begins with a selected standardized battery of tests with
relatively high sensitivity and low specificity. The screening battery presented
in Table 5–4 was recommended by Reichman (1994).
Table 5–4. Laboratory evaluation of dementia

Routine workup
Complete blood count
Electrolyte panel
Screening metabolic panel
Thyroid function tests
Vitamin B12 and folate levels
Tests for syphilis
Tests for human immunodeficiency virus antibodies, as indicated by history
Urinalysis
Electrocardiogram
Chest X ray
Additional studies to rule out specific conditions
Computed tomography (CT) of head—to rule out mass lesion, normal-pressure
hydrocephalus, recent bleed
Magnetic resonance imaging of head—same indications as for CT; is more
sensitive for ischemia or infarction, subcortical or brain-stem pathology
Electroencephalogram—to evaluate ictal or episodic features of history or
mental status examination
Lumbar puncture—to rule out central nervous system infection suggested by
physical examination
Positron emission tomography and single photon emission computed
tomography—to differentiate Alzheimer’s disease from other dementing
illnesses
Neuropsychological Tests
Neuropsychological tests are often performed to corroborate an impression of
dementia and to identify specific cognitive strengths and weaknesses that may
affect treatment or placement. Table 5–5 summarizes some of the tests that we
have found useful in diagnostic assessment for possible dementia. Each of these
tests has been developed for measures applicable to geriatric populations or has
been studied extensively with older patients. Other measures may be useful as
well, but any battery for dementia evaluation should tap a full range of cognitive
abilities, including general intelligence, attention, language, learning and mem-
ory, visuospatial performance, and reasoning or problem solving. If coexisting
psychiatric disturbance is suspected, psychodiagnostic measures also should be
included (see Chapter 3, “Mood Disorders—Diagnosis”).
Neuropsychological testing alone is generally not sufficient to establish a
particular etiology of dementia. However, the pattern of performance on
these tests can either strengthen or weaken the case for certain types of de-
mentia. For example, on tests of learning and memory, a very shallow learning
curve, sharply reduced delayed recall, and impaired recognition are com-
monly observed in dementia of the Alzheimer’s type but are less often noted
in subcortical dementia (e.g., Huntington’s chorea or Parkinson’s disease), in
frontotemporal dementia, or in major depression.
Common Etiologies of Dementia

Dementia may result from a diverse set of disorders and conditions; some dis-
orders invariably produce a dementia (e.g., Alzheimer’s disease), whereas others
result in dementia only in some cases. For some etiologies, dementia is chronic,
progressive, and irreversible by currently available approaches, whereas for other
causes of dementia, symptoms may be arrested or reversed to varying degrees
with specific treatments. Table 5–6 lists general medical conditions and medi-
cations that can produce symptoms of dementia. In general, the list of factors
capable of causing dementia increases with the age of the patient, as declining
functional brain reserve reduces the individual’s ability to tolerate physiological
derangement. The remainder of this chapter and the next chapter are devoted
to the differential diagnosis of dementia, beginning with the most common
cause of dementia—Alzheimer’s disease.
Table 5–5. Examples of neuropsychological assessment instruments
Test Description Functions assessed Interpretation Comment
Wechsler Adult General adult Verbal and nonverbal IQ scores lower than Influenced by education
Intelligence Scale— intelligence battery skills, including estimated baseline or
Third Edition with 14 subtests; vocabulary, attention, low age-scaled subtest
(WAIS-III) normed to age 89 reasoning, perceptual scores may indicate
organization, and impairment
processing speed
Wechsler Memory Battery of verbal and Orientation; mental Low scores on immediate Sensitive to mild
Scale—Third Edition nonverbal memory control; memory span; or delayed memory amnesia, dementia

(WMS-III) tests; normed to age 89 immediate and delayed indices may indicate
recall of stories, word impairment
pairs, faces, scenes, and
abstract designs
California Verbal Memorization of a 16- Short-term and Slow rate of learning or Sensitive to mild cortical
Learning Test (CVLT) item shopping list; secondary (recent) impaired delayed recall and subcortical
normed to age 80 memory; strategy use, suggests amnestic dementia
benefits of cues, deficit; forgetfulness
recognition; effect of suggested by better
interference cued than free recall,
good recognition
memory
187
Table 5–5. Examples of neuropsychological assessment instruments (continued)

Consortium to Establish Memorization of a list of Verbal learning and Slow rate of learning or Sensitive to mild
a Registry for 10 words; developed delayed recall impaired delayed recall dementia of the
Alzheimer’s Disease and normed for older suggests amnestic Alzheimer’s type; easier
(CERAD) Word List adults deficit than CVLT
Learning
Object Memory Memorization of 10 Storage and retrieval Delayed recall <50% or Good test of secondary
Evaluation common objects; from secondary very low rate of learning memory for patients
normed for ages 70–90 memory, delayed recall suggests amnestic with low education level
and recognition deficit
Boston Naming Test Naming of drawings of Confrontation naming, Cutoff scores vary with More sensitive to mild
(BNT) objects; normed to age access to semantic age and education anomic aphasia than is
90+ memory mental status
examination
Controlled Oral Word Naming of words Verbal fluency, access to Cutoff scores vary with Intrusions may be noted
Association Test beginning with semantic memory, age and education in early Alzheimer’s
(COWAT) specified letters; ability to organize rapid disease, perseverations
normed to age 90+ retrieval or loss of set in
subcortical dementias
Table 5–5. Examples of neuropsychological assessment instruments (continued)
Trail Making Test (TMT) Lines drawn to connect Composite index of Cutoff scores vary with Failure on alternating
number and letter visual scanning speed, age and education sequence noted in mild
sequences; normed to sequencing, mental brain impairment of
age 80+ flexibility, visuomotor various types; slowing
integration in subcortical dementia
Wisconsin Card Sorting Sorting of Inferring concepts, Cutoff scores vary with May be more sensitive
Test (WCST) multidimensional cognitive flexibility age and education than memory tests to
patterns into frontotemporal and

categories; normed to subcortical dementias
age 80
Note. For references to tests and further discussion, see La Rue A: “Geriatric Neuropsychology: Principles of Assessment,” in Handbook of Assessment in
Clinical Gerontology. Edited by Lichtenberg PA. New York, Wiley, 1999, pp. 381–416; Spreen O, Strauss E (eds): A Compendium of Neuropsychological
Tests, 2nd Edition. New York, Oxford University Press, 1998; and Lezak M, Howieson D, Loring D: Neuropsychological Assessment, 4th Edition. New
York, Oxford University Press, 2004.
189
Table 5–6. General medical conditions and substances that can

produce symptoms of dementia
General medical conditions
Dementia syndrome of depression
Endocrine disorders
Thyroid diseasea
Parathyroid disease
Adrenal disease
Pituitary disease
Infections
Acquired immunodeficiency syndromea
Creutzfeldt-Jakob disease and other viral and prion encephalitides
Cryptococcosis
Encephalitis
Leptomeningitis
Neurosyphilis
Progressive multifocal leukoencephalopathy
Neurological disorders
Alzheimer’s diseasea
Amyotrophic lateral sclerosisb
Cerebellar and spinocerebellar degeneration
Huntington’s chorea
Dementia with Lewy bodiesa
Multiple system atrophy
Normal-pressure hydrocephalus
Olivopontocerebellar degeneration
Parkinsonism-dementia complex of Guam
Parkinson’s diseasea
Pick’s diseaseb
Progressive subcortical gliosisb
Progressive supranuclear palsy
Nutritional disorders
Folate deficiency
Pellagra
Table 5–6. General medical conditions and substances that can

produce symptoms of dementia (continued)
Nutritional disorders (continued)
Pernicious anemia
Thiamine deficiencya
Space-occupying lesions
Brain tumor, primary and metastatica
Chronic subdural hematoma
Obstructive hydrocephalus
Systemic disorders
Anemia
Paraneoplastic dementia
Pulmonary disease with hypoxia or hypercarbia
Vascular disorders
Atherosclerosis, arteriosclerosisa
Hypertensiona
Repeated episodes of cerebral ischemia or hypoxiaa
Vasculitis
Substances
Medications
Antihypertensives
Corticosteroids
Digitalis
Opiates and synthetic narcoticsa
Psychoactive agents with anticholinergic propertiesa
Other chemicals
Carbon disulfide
Carbon monoxide
Lead
Manganese
Mercury
Most drugs of abuse
a
Common offender.
bPatient
may present as having “frontotemporal dementia.”
Alzheimer’s disease, including both early-onset (age 65 or younger, account-
ing for about 1% of all Alzheimer’s disease cases) and late-onset (older than
65) subtypes, accounts for about 50% of all cases of primary dementia and
may combine with other conditions, primarily vascular dementia, in another
10%–20% (Langa et al. 2004). Because the definitive diagnosis of Alzhei-
mer’s disease requires direct visualization of characteristic neuropathology
(i.e., amyloid β-peptide–containing senile plaques, neurofibrillary tangles
[NFTs] consisting of hyperphosphorylated tau protein, neuritic degeneration
and loss) in brain tissue of affected patients and brain biopsy is prohibitively
risky, Alzheimer’s disease is at best a probable diagnosis in the living patient.
Epidemiology—Risk Factors and Protective Factors

Age is the major risk factor for Alzheimer’s disease, which is rare before age 50
and uncommon in early old age, but prevalence climbs steeply after age 65. Es-
timates of prevalence vary depending on the extent of diagnostic workup per-
formed and whether mild (i.e., possible) cases are included in the survey (see
Figure 5–1). Conservative estimates suggest that 1 in 20 persons age 65 and
older, 1 in 4 persons age 80 and older, and half of persons age 95 and older have
Alzheimer’s disease. The risk of “sporadic” (as opposed to “familial”; see subsec-
tion “Genetics of Alzheimer’s Disease” later in this chapter) disease is increased
in persons with a history of head injury and is very high in individuals with
Down syndrome who survive to middle age. Diabetes, hypertension, hypercho-
lesterolemia, atherosclerotic cerebrovascular disease, obesity, and other factors
also have been associated with increased risk of Alzheimer’s disease. Rates of di-
agnosis of Alzheimer’s disease in women are higher than in men, and persons
with minimal education are at increased risk (Katzman 1993).
The other well-established risk factor for Alzheimer’s disease is the apoli-
poprotein ε4 allele (APOE4). There are three alleles— ε2, ε3, and ε4—of the
gene on chromosome 19, which codes for the production of apolipoprotein,
a substance involved in cholesterol metabolism and probably in neuronal pro-
tection and repair. Presence of one ε4 allele is associated with about 2.5 times
the risk of developing Alzheimer’s disease (compared with those homozygous
for the ε3 allele), and presence of two ε4 alleles is associated with a 12- to 15-
fold risk of developing Alzheimer’s disease. This effect of APOE4 is mediated
Prevalence of Alzheimer’s disease (%)
Age (years)
Figure 5–1. Prevalence of Alzheimer’s disease in the Framingham Study

and the East Boston Study.
Source. Data from Bachman et al. 1992 and Evans et al. 1989.
in part by earlier onset of Alzheimer’s disease in those who are APOE4 posi-
tive, and it is attenuated in black and Hispanic individuals (Harwood et al.
2004). APOE4 is also associated with the presence of concomitant Lewy bod-
ies in autopsy studies of patients with Alzheimer’s disease (Tsuang et al. 2005),
decreased longevity, increased plasma cholesterol levels, and prevalence of car-
diovascular disease and tends to worsen response to head trauma, age-related
cognitive decline, and several other disorders (Smith 2000).
In a meta-analysis of 11 retrospective and prospective studies, Szekely et al.
(2004) concluded that long-term exposure to nonsteroidal anti-inflammatory
drugs (NSAIDS) is associated with a reduced risk for developing Alzheimer’s
disease. The literature reviewed did not allow any conclusions regarding which
NSAIDs are best, and the most effective duration of treatment or dosage of
medication is unknown. Hormone replacement therapy (estrogen with or with-
out progestins) in postmenopausal women was reported to reduce the risk of
developing Alzheimer’s disease (LeBlanc et al. 2001). This observational report
was contradicted by the Women’s Health Initiative Memory Study, a random-
ized, double-blind, placebo-controlled primary prevention trial in women age
65 years or older, which found that estrogen with or without progestin increased
the risk of developing both Alzheimer’s disease and mild cognitive impairment
(Shumaker et al. 2004). A possible explanation for these discrepant findings was
reported by Henderson et al. (2005), who found that hormone replacement
therapy was protective against the development of Alzheimer’s disease, but only
in women ages 50–63; older subjects did not sustain the same benefit.
The risk of developing Alzheimer’s disease also appears to be reduced in
people who ingest adequate amounts of the antioxidants vitamin E and vita-
min C, in food or supplement form, according to several investigators. Engel-
hart et al. (2002) reported findings from the Rotterdam study and concluded
that “high intake of vitamin C and vitamin E from food may be associated
with a lower incidence of Alzheimer disease after a mean follow-up period of
6 years” (p. 3228, emphasis added). In this study, vitamin E and C supple-
ments did not reduce the risk of Alzheimer’s disease. However, Zandi et al.
(2004) did find a significantly lower incidence and prevalence of Alzheimer’s
disease in individuals who ingested the combination of supplemental vitamin
E (400 IU/day or more) and vitamin C (at least 500 mg/day of ascorbic acid),
but not either vitamin alone, over a 3-year follow-up period.
Morris and colleagues (2005) reported data that may partially resolve the dis-
agreement between the two studies discussed in the prior paragraph. They fol-
lowed up 1,041 subjects age 65 or older for a median of 3.9 years and found that
dietary α-, γ-, and δ-tocopherols were significantly and inversely associated with
incident Alzheimer’s disease, with reductions in risk of 34% per 5-mg/day in-
crease in α-tocopherol, 40% per 5-mg/day increase in γ-tocopherol, and 25% per
1-mg/day increase in δ-tocopherol. There was no evidence of an association be-
tween intake of β-tocopherol and Alzheimer’s disease risk. The authors concluded
that “various tocopherol forms rather than α-tocopherol alone may be important
in the vitamin E protective association with Alzheimer disease” (p. 508).
Several cross-sectional observational studies raised the possibility that
statins, which reduce cholesterol, might reduce the risk of Alzheimer’s disease.
To examine this relation, Zandi et al. (2005) followed up with 4,895 partici-
pants in the Cache County Study, an investigation of the genetic and envi-
ronmental antecedents of dementia among the elderly population of Cache
County, Utah, which began in 1995 with the enrollment of 5,092 individuals
age 65 or older. Statin use was less frequent in subjects with prevalent dementia,
but the authors found no association between statin use and subsequent onset
of dementia or Alzheimer’s disease. This finding is surprising given the known
relation between atherosclerosis and cerebrovascular disease. The authors ac-
knowledged several methodological and statistical factors that may have ob-
scured a real association, among them the short duration (about 3 years) of
exposure to statins, the small number of subjects who reported taking statins,
and the small number who developed Alzheimer’s disease. The role of statins in
the prevention of dementia and Alzheimer’s disease remains to be determined.
Diagnostic Criteria
In DSM-IV-TR (American Psychiatric Association 2000), the term dementia
of the Alzheimer’s type is applied to patients whose condition meets clinical and
laboratory criteria for probable Alzheimer’s disease; dementias associated with
other neurological diseases (e.g., Pick’s disease or Creutzfeldt-Jakob disease)
are coded separately. General criteria for dementia must be met, and a history
of insidious onset and gradual progression must be present; if all other causes
of dementia are ruled out by the history, physical examination, and laboratory
tests, dementia of the Alzheimer’s type is diagnosed (Table 5–7).
NINCDS Criteria
The National Institute of Neurological and Communicative Disorders and
Stroke (NINCDS) published a set of diagnostic criteria for research purposes
that are somewhat more narrow than the DSM-IV-TR criteria (McKhann et
al. 1984). Separate standards are listed for the clinical diagnosis of probable
and possible Alzheimer’s disease (Table 5–8).
Neuropathological Criteria
At present, at least three pathological criteria for Alzheimer’s disease are inter-
nationally acceptable: 1) Braak’s criteria (Braak and Braak 1991); 2) Consor-
tium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria (Mirra
et al. 1991) and their combination; and 3) National Institute on Aging and
Table 5–7. Summary of DSM-IV-TR diagnostic criteria for

dementia of the Alzheimer’s type
A. The development of multiple cognitive deficits manifested by both
(1) memory impairment
(2) one (or more) of the following cognitive disturbances:
(a) aphasia
(b) apraxia
(c) agnosia
(d) disturbance in executive functioning
B. These deficits cause significant impairment in social or occupational functioning
and represent a significant decline from a previous level of functioning.
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits are not due to any of the following:
(1) other central nervous system conditions that cause progressive deficits in
memory and cognition
(2) systemic conditions known to cause dementia
(3) substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.
F. The disturbance is not better accounted for by another Axis I disorder.
Ronald and Nancy Reagan Institute of the Alzheimer’s Association criteria

(National Institute on Aging and Reagan Institute Working Group on Diag-
nostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease
1997). Braak’s criteria are based on the distribution of NFTs (described in the
subsection “Neuropathology of Alzheimer’s Disease” later in this chapter) as
Alzheimer’s disease progresses: NFTs first appear in the transentorhinal area
(stage I), spread to the entorhinal region (stage II), extend to the hippocam-
pus proper (stage III), increase in number there (stage IV), and then involve
the association neocortex (stage V) and finally the primary cortex (stage VI).
The CERAD pathological criteria are based on the density of neuritic
plaques (also discussed in the subsection “Neuropathology of Alzheimer’s
Disease” later in this chapter) in three areas: 1) the second frontal gyrus at the
level of the caudate-putamen complex, 2) the first temporal gyrus at the level
of the amygdala, and 3) the supramarginal gyrus with parieto-occipital sulcus.
Density is rated as follows: stage A =less than 2, stage B =approximately 6, and
stage C = more than 30 neuritic plaques per 100× light microscopic field.
Alzheimer’s disease is diagnosed when stage A is identified in patients younger
than 50 years, when stage B is seen in patients between 50 and 75 years, and
when stage C occurs in patients older than 75 years, along with a definite clin-
ical history of dementia (Murayama and Saito 2004).
As is true for all dementing illnesses, the clinical presentation of Alzheimer’s
disease depends on the stage of illness and may be obscured or complicated
by symptoms related to concomitant physical and psychiatric illness, in-
cluding depressive or anxiety disorders, psychosis, and delirium. Table 5–9
summarizes the clinical and laboratory findings typically observed in uncom-
plicated cases as the disease progresses (Group for the Advancement of Psy-
chiatry 1988). Functional symptoms nearly indistinguishable from those of
concomitant psychiatric illness are part of the presentation of Alzheimer’s dis-
ease, even in the early stages, and patients may present to general psychiatric
clinical settings. Gormley and Rizwan (1998) reported that one-third of
Alzheimer’s disease patients had delusions, and 11% had hallucinations
within the month before evaluation, and this prevalence was not affected by
severity of dementia or of depressive symptoms. Farber and colleagues (2000)
found that 63% of patients with Alzheimer’s disease had psychosis at some
point in the course of illness and that those with psychosis had 2.3 times the
density of neocortical NFTs than did those without psychosis. In some pa-
tients with Alzheimer’s disease, the psychosis is clinically prominent enough
to obscure the underlying cognitive impairment and delay accurate diagnosis.
Delusions are usually persecutory in nature and are typically fragmented
and inconsistent, unlike those seen in the common functional disorders (e.g.,
schizophrenia, delusional disorder, or mood disorder with psychosis). Com-
mon delusional content includes the belief that one is being threatened,
deprived, or abused by caregivers or that possessions are being stolen; hypo-
chondriacal delusions and Capgras’ syndrome are also common (Migliorelli
et al. 1995). Delusions in Alzheimer’s disease typically do not have the elab-
orate “connectedness” seen in functional delusions (i.e., the myriad ways in
Table 5–8. Criteria for clinical diagnosis of Alzheimer’s disease

from the NINCDS-ADRDA Work Group
Probable Alzheimer’s disease
Dementia: established by clinical examination; documented by Mini-Mental

State Examination, Blessed Dementia Scale, or similar examination;
confirmed by neuropsychological tests
Deficits in two or more areas of cognition
Progressive loss of memory and cognitive functions
No disturbance of consciousness
Onset between ages 40 and 90
Absence of systemic disorders or other brain diseases that in and of themselves
could account for deficits
Diagnosis of probable Alzheimer’s disease supported by

Progressive loss of specific cognitive functions (e.g., language, motor skills,
perception)
Impaired activities of daily living and altered behavior patterns
Family history of similar disorders, especially if neuropathologically
confirmed
Laboratory results of normal lumbar puncture; normal or nonspecific
changes on electroencephalogram
Computed tomography—cerebral atrophy with progression documented by
serial observation
Other features consistent with probable Alzheimer’s disease

Plateaus in course of progression of illness
Associated symptoms (e.g., depression, incontinence, weight loss)
Seizures in advanced disease
Computed tomography normal for age
Probable Alzheimer’s disease uncertain if

Sudden onset; focal neurological findings; seizures or gait disturbance early
in course of illness
Table 5–8. Criteria for clinical diagnosis of Alzheimer’s disease

from the NINCDS-ADRDA Work Group (continued)
Possible Alzheimer’s disease
Dementia syndrome in absence of other causes and in presence of variations in

onset, presentation, or clinical course
A second systemic or brain disorder sufficient to produce dementia but not
considered the cause
Single, gradually progressive, severe cognitive deficit
Definite Alzheimer’s disease
Clinical criteria for probable Alzheimer’s disease with neuropathological

confirmation
Subtypes
Familial
Onset before age 65
Presence of trisomy 21
Other relevant disorders (e.g., parkinsonism)
Note. ADRDA =Alzheimer’s Disease and Related Disorders Association; NINCDS= National
Institute of Neurological and Communicative Disorders and Stroke.
Source. Adapted from McKhann et al. 1984.
which the patient is able to tie the delusional belief to all aspects of his or her
experience), and hallucinations—usually auditory but sometimes visual, ol-
factory, or tactile—are intermittent and of varying and usually trivial content,
lacking the ordered, meaningful quality typical of functional hallucinations.
Depressive symptoms and apathy occur in about 20%–25% of Alzhei-
mer’s disease patients at any given time (Lyketsos et al. 2000b), but full de-
pressive syndromes (e.g., major depression) are relatively rare.
History
The history of Alzheimer’s disease is typically one of insidious onset and
gradual progression of cognitive and functional impairment, with few of the
Table 5–9. Natural history of Alzheimer’s disease: clinical and laboratory findings

Function/test Early cognitive decline Moderate cognitive decline Severe cognitive decline
Orientation Fully oriented Frequent mistakes, but usually Severe disorientation

knows date, familiar persons
Concentration Mild deficits; some errors in Moderate deficits; usually has Can barely count to 10
serial calculation difficulty counting backward
Recent memory Misplaces items; forgets names, Poor knowledge of current and Unaware of almost all recent
recent events recent events experiences
Remote memory Some deficits in recall of remote Many deficits in recall of remote Almost no recall of any past events
events events
Language and speech Word-finding problems, poor Limited vocabulary and sentence Fluent aphasia with unintelligible
word-list generation, mild structure, repetitive speech
anomia
Praxis Normal to minimal deficit Ideomotor apraxia; difficulty Cannot feed or toilet self
with finances, hobbies,
marketing
Visuospatial skills May get lost in unfamiliar Poor constructions and spatial Agraphia; may have neurological
settings; poor construction disorientation; can travel to signs
on tests familiar places
Self-care Normal May require assistance choosing Requires assistance in multiple
clothing; may need coaxing to spheres; occasional or persistent
bathe problems with bladder or bowel
incontinence
Table 5–9. Natural history of Alzheimer’s disease: clinical and laboratory findings (continued)
Function/test Early cognitive decline Moderate cognitive decline Severe cognitive decline
Complex or new tasks Decreased performance Decreased performance; may Cannot perform
withdraw from challenging
situations
Personality Possible apathy, depression, Denial common; apathy and Agitation or anxiety, psychosis,
or irritability indifference abulia, obsessiveness
CT scan Normal Normal to atrophic cortices and Cortical atrophy and ventricular
dilated ventricles enlargement
EEG Normal Background slowing Diffuse slowing

PET and SPECT Bilateral temporoparietal Bilateral temporoparietal Bilateral temporoparietal and frontal
hypoperfusion hypoperfusion hypoperfusion
Note. CT=computed tomography; EEG= electroencephalogram; PET=positron emission tomography; SPECT= single photon emission computed to-
mography.
Source. Copyright 1988 from The Psychiatric Treatment of Alzheimer’s Disease by Group for the Advancement of Psychiatry. Reproduced by permission
of Routledge/Taylor & Francis Group, L.L.C.
201
sharp downward steps in function typical of vascular dementia or the more

abrupt onset and rapid progression of the dementia syndrome of depression.
Unlike frontotemporal dementia, memory impairment (especially the ability
to recall new information after a short delay [Welsh et al. 1991]) is invariably
present and is often the presenting symptom. Later, marked impairments in
expressive and receptive language, ability to plan and organize activities, and
virtually all other aspects of cognition are affected. The rate of progression
of cognitive impairment varies among individuals, but a decline of 2–3
points per year on the Folstein MMSE is typical. Some studies find nonlin-
ear progression, with less rapid decline in the early and late stages and rela-
tively more rapid decline in midcourse. Functional decline generally parallels
cognitive decline, but basic activities of daily living tend to be preserved until
cognitive function has reached the “moderately impaired” stage, whereas in-
strumental activities of daily living are affected earlier. Perhaps because of
this slow progression, in the early stages, cognitive deficits often can be con-
cealed or compensated for, and friends and family who have only superficial
interactions with patients may be unaware of relatively major deficits. Some-
times close family members who have observed declining cognition attempt
to rationalize away the significance of their observations. Because of these
possibilities, multiple sources of historical data may be necessary to establish
a reliable history.

Some of the major mental status findings typical of each stage of Alzheimer’s
disease are included in Table 5–9. Although relatively synchronous decline in
cognitive capacities is the general rule, in some patients, language disturbance
may be severe enough to prevent accurate evaluation of memory and higher
cognitive functions; similarly, suspiciousness or social withdrawal may lead to
an exaggerated estimate of the degree of cognitive decline in a relatively intact
individual.
In probable Alzheimer’s disease, multiple neuropsychological impairments
are seen, including anomic or mixed aphasia, apraxia, deficits in reasoning,
and prominent learning and memory impairment. Patients with Alzheimer’s
disease rapidly forget new information and often do not benefit from cueing
or memory reminders, implying deficits in encoding or learning as well as

problems with retrieval. Early in the course of illness, neuropsychological def-
icits may be restricted to one or two areas—most often, learning and memory.
Brief versions of tests like those described in Table 5–5 have been combined
by CERAD to form a screening battery that may be useful in detecting and
staging Alzheimer’s disease (Welsh et al. 1994).
List-learning tasks are among the most sensitive for detecting the mem-
ory deficits of early Alzheimer’s disease and for differentiating such deficits
from the milder memory changes of age-associated memory impairment.
Table 5–5 describes three such tasks, including Word List Learning from the
CERAD battery. No single cutoff score can be used to classify impairment
on learning tasks; rather, results for individuals must be interpreted relative
to normative tables for age and education level.
Laboratory evaluation of Alzheimer’s disease is the same as that described ear-
lier in this chapter for dementia (Table 5–4). Despite the promise of the ex-
perimental diagnostic procedures discussed in the following subsection, the
laboratory evaluation of patients with possible Alzheimer’s disease is primarily
aimed at ruling out other causes of dementia. If this evaluation does not iden-
tify another cause of dementia, and either DSM-IV-TR or NINCDS–Alzhei-
mer’s Disease and Related Disorders Association clinical criteria are applied,
the diagnosis of “probable Alzheimer’s disease” has reasonable sensitivity (ap-
proximately 80%) and specificity (approximately 70%), as confirmed by sub-
sequent neuropathological diagnosis (Knopman et al. 2001).
Advanced and Experimental Diagnostics

Research studies that used single photon emission computed tomography
(SPECT), positron emission tomography (PET) measuring glucose metabo-
lism or amyloid burden, magnetic resonance spectroscopy, magnetic reso-
nance imaging (MRI), functional magnetic resonance imaging (fMRI) with
activation, measurement of cerebrospinal fluid antigens, and analysis of apo-
lipoprotein alleles all have produced promising results.
Dougall et al. (2004) reviewed the diagnostic accuracy of SPECT in
Alzheimer’s disease and concluded that “diagnostic accuracy can be improved
with SPECT in dementia patients who present with possible comorbid
symptoms of vascular disease or who do not entirely conform to clinical

criteria …especially in ruling in AD [Alzheimer’s disease] as a cause when the
SPECT result is positive and vice versa” (p. 562). Patwardhan and colleagues
(2004) used rigorous inclusion criteria to conduct a meta-analysis of nine
studies in which the operating characteristics of PET were assessed in the di-
agnosis of Alzheimer’s disease. Although specificity and sensitivity were both
estimated at 86%, the authors found several methodological problems in the
studies that they believed limited the validity and therefore the utility of their
results. Kulasingam et al. (2003) analyzed the available PET data in light of
the risk-benefit ratio of available treatments for Alzheimer’s disease and con-
cluded that cholinesterase inhibitors (discussed in the subsection “Cholines-
terase Inhibitors” later in this chapter) should be prescribed on the basis of the
history, physical examination, neuropsychiatric evaluation, and structural
neuroimaging to rule out other causes of dementia, without recourse to PET
or SPECT imaging and examination. If treatments entailing more serious risk
are developed, the addition of PET to the diagnostic battery would be war-
ranted. Despite their limitations, both SPECT and PET appear to have a role
in the evaluation of some cases of suspected Alzheimer’s disease, although spe-
cific indications have yet to be published.
Klunk and associates (2004) used PET to study the distribution of labeled
Pittsburgh Compound-B (PIB), a benzothiazole, thioflavin-T derivative that
crosses the blood-brain barrier and binds to amyloid β-peptide. They found
PIB to be a reliable marker of amyloid in vivo and proposed a possible future
role for the PET-PIB procedure in the diagnosis and staging of Alzheimer’s
disease, as well as for assessment of anti-amyloid treatment response. de Leon
and colleagues (2004) conducted a series of studies in which MRI and cere-
brospinal fluid biomarkers were used to diagnose Alzheimer’s disease, and re-
sults were promising but not yet applicable to the clinical setting. Dickerson
and associates (2004) studied memory-associated activation of the medial
temporal lobe regions with fMRI in subjects with mild cognitive impairment
and found that greater activation was associated with better memory perfor-
mance. However, the subjects who recruited the largest area of the parahip-
pocampal gyrus were the most impaired at baseline; more important, the
44% who deteriorated over the ensuing 2.5 years (more than 25% of whom
developed probable Alzheimer’s disease) activated significantly larger areas of
the parahippocampal gyrus despite similar memory performance. These in-
vestigators concluded that greater activation of the parahippocampal gyrus

may be compensating for greater Alzheimer’s disease pathology and could be
a diagnostic sign of impending Alzheimer’s disease. Finally, Mayeux and col-
leagues (1998) studied the diagnostic value of the presence of APOE4 in a
sample of 2,188 patients with dementia who underwent autopsy. The clinical
diagnosis of Alzheimer’s disease had 93% sensitivity and 55% specificity,
compared with 65% and 68%, respectively, for APOE4 alone. However, add-
ing APOE4 data to the clinical diagnosis increased the specificity to 84% but
lowered the sensitivity. To date, these and other experimental approaches have
not reached the stage of widespread acceptability in the diagnosis of Alzhei-
mer’s disease.
Differential Diagnosis of Alzheimer’s Disease

Functional Disorders
Certain functional conditions can mimic Alzheimer’s disease. They include de-
pressive pseudodementia (see Chapter 3, “Mood Disorders—Diagnosis”), mania,
hypomania, personality disorder, Ganser syndrome, hysteria, and malingering. In
most patients, the signs and symptoms of functional illness are clear, cognitive im-
pairment is readily identified as secondary, and diagnostic error is easily avoided.
Nevertheless, some cases of depression can be particularly misleading, and several
authorities have recommended antidepressant treatment trials in selected patients
(see related discussion in Chapter 4, “Mood Disorders—Treatment”).
Other Dementias
Alzheimer’s disease must be distinguished from the other degenerative dementias
such as frontotemporal dementia and dementia with Lewy bodies, vascular de-
mentia, and the dementias due to general medical conditions and substances.
These are all discussed in detail in Chapter 6 (“Other Dementias and Delirium”).
Amnestic Disorders
Amnestic disorders can be misdiagnosed as dementia, even though in amnes-
tic disorder, intellectual functions other than memory are spared. The most
common amnestic disorder in elderly patients is Korsakoff ’s psychosis, which
is caused by prolonged thiamine deficiency usually associated with long-term,
high-dose ingestion of alcohol. In addition to sparing of intellect, confabula-
tion is often a prominent feature of this syndrome.
Delirium
Alzheimer’s disease is usually easily differentiated from delirium, which has a
much more acute onset and progression and entails more severe impairment
of attention and concentration and more disorganization of thought. How-
ever, delirium superimposed on Alzheimer’s disease may be more difficult to
diagnose, often requiring reevaluation after potential causes of delirium have
been eliminated and the underlying dementia has been allowed to emerge.
Neuropathology of Alzheimer’s Disease

The gross neuropathology of Alzheimer’s disease consists of cortical atrophy,
particularly involving anterior frontal and temporoparietal areas. Microscopic
findings include NFTs, senile plaques, and granulovacuolar degeneration.
Neurofibrillary tangles are densely packed microfibrils found in the cyto-
plasm of dead neurons. Under an electron microscope, these microfibrils have
been shown to consist of paired helical filaments, composed primarily of an ab-
normally phosphorylated tau protein, that are 100 Å wide and twist every 800 Å.
Senile plaques are extracellular deposits of the 42–amino acid amyloid β-
peptide that is derived from the amyloid precursor protein (APP). They are
5–150 µm in diameter and appear in three major forms: 1) diffuse plaques,
which consist of formed filamentous and nonstructured amyloid β-peptide
without attached abnormal neurites; 2) neuritic plaques, which are composed
of dense bundles of amyloid fibrils and dystrophic neurites (usually contain-
ing paired helical filaments); and 3) “burned out” plaques, in which a dense
amyloid core is surrounded by reactive astrocytes but no abnormal neurites.
A “primitive” form of neuritic plaque lacking the amyloid component of the
core also has been described (Terry et al. 1994). APP is a transmembrane pro-
tein that is present in almost all tissues. It undergoes proteolytic cleavage by
α-, β-, and γ-secretase enzymes to generate either nonamyloidogenic or amy-
loidogenic peptides. When full-length APP is cut by α-secretase and then by
γ-secretase, it generates a harmless peptide, but when APP is cut by β-secre-
tase and then by γ-secretase, it generates peptides of 39–43 amino acids, of
which amyloid β-peptide 1–40 is the most common and considered harmless,
whereas amyloid β-peptide 1–42, which accounts for about 10% of amyloid
β-peptide, is neurotoxic and involved in the formation of senile plaques in
Alzheimer’s disease brains (Kamboh 2004).
Granulovacuolar degeneration primarily affects hippocampal pyramidal

neurons and consists of groups of intracytoplasmic vacuoles about 5 µm in
diameter, each containing a small granule.
Other histopathological findings in Alzheimer’s disease include congo-
philic angiopathy, consisting of amyloid deposits in the walls of small arteries
of the frontal and parietal cortex, and generalized loss of neuronal dendrites
in affected cortical areas. Loss of cholinergic neurons of the nucleus basalis of
Meynert, loss of noradrenergic neurons of the locus coeruleus, and loss of se-
rotonergic neurons of the dorsal raphe nucleus also have been described. The
first two changes have been correlated with reduced cortical tissue levels of
choline acetyltransferase and norepinephrine and its metabolites, respectively
(discussed in the next section below, “Neurobiochemistry of Alzheimer’s Dis-
ease”); reduced cortical concentrations of serotonin have been less consis-
tently reported. Other investigators have identified synaptic loss, neuronal
loss, and volume reduction in the hippocampus that is detectable with MRI
(de Leon et al. 2004).
Neurobiochemistry of Alzheimer’s Disease

The first and most thoroughly confirmed neurobiochemical abnormality
found in brain tissue affected by Alzheimer’s disease neuropathology was re-
duced temporoparietal and hippocampal cortical activity of choline acetyl-
transferase, an enzyme found only in cholinergic cells, which catalyzes the
synthesis of acetylcholine. Biopsy studies have detected significant losses of
this enzyme as early as the first symptomatic year, and autopsy studies have
reported a strong correlation (r=0.8) between the degree of choline acetyl-
transferase loss and premortem measurements of cognitive and functional
decline. Concentrations of acetylcholinesterase and acetylcholine, both of
which are less specific indicators of cholinergic cell activity than is choline
acetyltransferase, also have been found to be reduced in affected brain tissue.
Altogether, these findings support a working analogy between Alzheimer’s
disease and Parkinson’s disease, in which a single neurotransmitter (dopa-
mine) is also deficient. This analogy ultimately led to the development of
tacrine, donepezil, and other acetylcholinesterase inhibitors (see subsection
“Cholinesterase Inhibitors” later in this chapter), which are modestly effective
treatments for Alzheimer’s disease. However, less profound abnormalities in
other neurotransmitter systems have been documented (American Psychiatric

Association 2000), and at least one noncholinesterase inhibitor—meman-
tine—has been shown to be at least modestly effective in Alzheimer’s disease.
Genetics of Alzheimer’s Disease

Alzheimer’s disease is transmitted as an autosomal dominant trait in about
2% of all cases. In these familial cases, which typically have early onset, several
genes are responsible: one (presenilin 1), found in about half of Alzheimer’s
disease families, is on chromosome 14; two others—presenilin 2, on chromo-
some 1, and the gene that encodes for APP, on chromosome 21—are present
in far fewer Alzheimer’s disease families. Each of these genes in its pathologi-
cal variant results in abnormal β-APP processing with resultant overproduc-
tion of the amyloid β-peptide 42 (St George-Hyslop 2000). The other 98%
of individuals with Alzheimer’s disease have sporadic disease, which appears
to result from an interaction between a genetic vulnerability and environmen-
tal factors. Gatz et al. (1997) found a concordance rate for prevalence of
Alzheimer’s disease among monozygotic twin pairs of 67%, whereas the cor-
responding figure for dizygotic pairs was 22%. Pedersen et al. (2004) exam-
ined incident Alzheimer’s disease in a cohort of 662 twin pairs followed up
for 5 years and found a concordance rate of about 32% for monozygotic twins
and about 9% for dizygotic twins, regardless of whether onset was before or
after age 80. Studies of incidence are likely to find a lower concordance rate
than are studies of prevalence, because affected twins are not included in the
baseline sample.
Psychosocial Therapy for Persons With

Psychosocial therapies developed for persons with Alzheimer’s disease and
other dementias have attempted to minimize disruptive behaviors or increase
positive behaviors, support mood and a sense of well-being, or improve or
support memory. In early studies with a single dementia patient or a small
number of patients, behavior modification approaches using techniques such
as time-outs, activity diversion, and selective reinforcement were shown to be
effective in reducing urinary incontinence or reinstating important self-care
activities such as bathing or walking (Gatz et al. 1998). More recent work ad-
dressing behavior problems has used cued recall procedures adapted from the
cognitive rehabilitation literature; Bird and colleagues (1995) provide good
examples of successes and failures of this approach.
Reminiscence therapy, which involves the discussion of past activities,
events, and experiences, usually with the aid of tangible prompts such as pho-
tographs or music, has become an increasingly popular intervention. It can be
used by staff at activity centers and long-term-care facilities and lends itself to
involvement of family members. A recent review of the literature on reminis-
cence therapy in dementia found four controlled trials, all of which reported
beneficial effects on cognition or mood in comparison with no-treatment or
social-contact control subjects. However, studies were small in size, and all
used different types of reminiscence procedures (Woods et al. 2005).
Early studies of memory training for patients with dementia used tech-
niques developed for normal older adults (e.g., group or individual practice
of mnemonics such as visual imagery), and results showed either no benefit
or very circumscribed benefit. Recently, more promising results have been
demonstrated with the use of specialized training techniques (e.g., spaced re-
trieval) that have proven effective in work with memory-impaired brain-
injured populations. These interventions typically involve a relatively intense
initial encoding phase in which the person with dementia is asked to say or
do a to-be-remembered action repeatedly, with the interval between the cue
and the desired response gradually lengthened from immediately to over an
hour or more. In an interesting case study, Clare and colleagues (2001) de-
scribed how a 74-year-old man with mild but progressive dementia (MMSE
score decreased from 26 to 22 across the study period) was able to learn
name–face associations for 11 members of his social club, sustain recall of
nearly all these names with daily self-practice over 9 months, and still retain
7 or 8 names over the next 2 years with only weekly club visits to rehearse the
associations. Individualization of the training and selecting objectives that
meet a real-life need are thought to be important by many contemporary
researchers studying the limits and benefits of a cognitive rehabilitation
approach for dementia patients. However, there are also ongoing new inves-
tigations of the effects of predetermined training regimens for persons with
early Alzheimer’s disease, especially as an adjunct to cholinesterase inhibitor
therapies (e.g., Loewenstein et al. 2004).
The potential benefits of psychotherapy for persons with Alzheimer’s dis-

ease and other dementias are also undergoing a reexamination, with clinicians
beginning to more systematically combine techniques drawn from the reha-
bilitation literature with general psychotherapy procedures. The role of indi-
vidual psychotherapy in the overall medical management of Alzheimer’s
disease depends on the stage of illness, the patient’s premorbid pattern of ego
strengths and vulnerabilities, and the presence or absence of concomitant
functional complications. In general, supportive therapy is most useful in the
early stages of illness and is aimed at ameliorating the anxiety and loss of self-
esteem accompanying awareness and anticipation of lost cognitive capabili-
ties. Many patients at this stage of illness use primitive defenses, resulting in
characteristic symptom complexes such as accusations that family members
are stealing from them (denial and projection), hypercritical and hostile be-
havior directed toward family members (denial and displacement), and,
sometimes, multiple bizarre somatic complaints (somatization). For some of
these patients, the capacity for insight is preserved, and gentle interpretation
may lead to adaptive behavior change, particularly if accompanied by practi-
cal advice and encouragement. Later in the course of illness, individual psy-
chotherapy has more limited goals, often limited to provision of a constant,
caring, healing authority figure whose attention can have significant, if non-
specific, anxiety-relieving and mood-elevating effects (Group for the Ad-
vancement of Psychiatry 1988). Throughout the course of therapy, it may be
beneficial to view the coping with illness as a partnership between the patient
and family members and other key social support persons, with the degree of
responsibility for independent behavior gradually shifting from the individual
to these supportive others (Judd 1999). Adapting the process of therapy to
take diminished memory into account (e.g., spending the first minutes of
each session reviewing what was last discussed, sending home for review a
short outline of what was covered in each session, and writing out specific
suggestions for activities or coping approaches to practice at home) may also
increase the effectiveness of psychotherapy.
Psychosocial Therapy for Dementia Caregivers

Caring for a family member with Alzheimer’s disease or other dementia is
challenging at best and overwhelmingly stressful at worst. Increased levels of
depression and anxiety, higher use of psychotropic medications, poorer physi-

cal health, and increased mortality have all been documented for family care-
givers. Recognition of caregiver burden has led to numerous psychosocial in-
terventions aimed at alleviating stress and adverse health consequences. Early
forms of interventions such as peer support groups and education were found
to have only very small benefits when subjected to careful study. A second gen-
eration of caregiver interventions has included individual and family counsel-
ing, case management, skills training, and combinations of these approaches.
In general, multicomponent approaches that offer options to fit individual car-
egivers’ needs and relatively intensive as opposed to brief interventions have
been found to be most beneficial (Schulz et al. 2002). In the most ambitious
study of caregiver interventions to date in the United States, the multisite Re-
sources for Enhancing Alzheimer’s Caregiver Health (REACH) investigation
included a sample of over 1,200 caregivers. The meta-analysis of 6-month out-
comes found a significant decrease in caregiver burden for a diverse group of
active treatments (e.g., skills training, family-based in-home intervention, tele-
phone-linked computer consultation, coping-with-caregiving classes, and pro-
fessional-enhanced support groups) compared to usual care control (e.g.,
information packets and referrals), and caregivers consistently rated the inter-
ventions as helpful (Gitlin et al. 2003). Another encouraging result was that
African American and Hispanic caregivers benefited as much as white care-
givers in terms of reduced burden. However, the effect size associated with in-
terventions was modest (0.15 standard deviation), and some subgroups of
caregivers (e.g., men and well-educated persons) did not experience a signifi-
cant reduction in burden.
Researchers studying caregiver interventions have underscored the diver-
sity of caregiver backgrounds and needs and the persistent, yet changing,
stresses associated with the role, and they caution against one-size-fits-all ap-
proaches. Other recent research has shown that the distress experienced by
many caregivers may not be automatically alleviated when help is hired in the
home (Pot et al. 2005) or when the family member with dementia enters a
nursing home (Schulz et al. 2004). Spouses may have an especially difficult
time adjusting to the nursing home placement of a husband or wife (Schulz
et al. 2004).
Psychiatrists and other mental health professionals can offer the option of
family therapy for caregivers who are experiencing depression, anxiety, or
other clinically significant mental health symptoms. Family intervention can

be useful at all stages of Alzheimer’s disease (Jarvik and Winograd 1988).
Initially, key elements of family therapy include dissemination of practical
advice, provision of information and education, referral to appropriate com-
munity resources, and opportunities to express emotions and fears related to
the diagnosis. Later, family therapy may be more focused on amelioration of
caregiver anxiety, demoralization, and depression. In the final stages of illness,
consultation and support vis-à-vis the often painful decision to institutional-
ize and providing assistance with the process of grieving a lost loved one may
become the foci of family therapy. Being able to continue a supportive psy-
chotherapeutic relationship with the family over the long haul of caregiving
is ideal but often difficult to achieve. Being available by telephone for brief
follow-up contacts as the patient’s illness proceeds to advanced stages can help
to sustain a sense of support.
Systematically assessing the behavioral deficits in the patient and deter-
mining which deficits cause the most distress to the caregiver can be helpful
in the initial evaluation and in monitoring response to treatment. Brief struc-
tured questionnaires such as the Memory and Behavior Problems Checklist
and the NPI (see subsection “Other Rating Measures” earlier in this chapter,
and Appendix) can be completed by the caregiver or by a professional on the
basis of caregiver input. Memory loss per se is generally less distressing to care-
givers than are emotional and behavior problems such as depression, delu-
sions, belligerence, and agitation. Treatment of these associated symptoms
often can be the difference between continuation of home care and institu-
tionalization for a patient with dementia.
In therapeutic work with family caregivers, it is important to keep in
mind that the caregiving role, despite its demands, can be a source of gratifi-
cation and increased self-efficacy. Caregivers may derive satisfaction from re-
paying older relatives for their own past care or may feel relief from knowing
that their loved one is receiving the best possible care (Scharlach 1994). In
caring for older relatives who are frail or who have dementia, African Ameri-
can and Hispanic families rely more heavily on relatives and friends than do
white families and are less likely to place their older family members in nurs-
ing homes. In the REACH study, Hispanic women who were dementia care-
givers reported lower levels of caregiving stress, greater perceived benefits of
caregiving, and a greater use of religious coping than did their white counter-
parts (Coon et al. 2004). It is unclear whether such findings reflect cultural
differences in filial roles and obligations or limited knowledge of or access to
alternative means of care (Aranda and Knight 1997). In any family that has a
relative with dementia, the therapist must assess the possibility of caregiver
distress and provide information about in-home, community, and institu-
tional resources.
Organizations such as the Alzheimer’s Association offer information and
help-line support for dementia caregivers, and many self-help books and Web
sites are available. Examples of resources that can be helpful to caregivers, es-
pecially when used in conjunction with family therapy or other interventions,
are included at the end of this chapter, following the references.
Psychopharmacotherapy for Cognitive Decline in

Cholinesterase Inhibitors
Several cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galan-
tamine) are available for treatment of the cognitive deficits of mild to mod-
erate Alzheimer’s disease. All of these agents increase central cholinergic
neurotransmission by inhibiting breakdown of acetylcholine by acetylcho-
linesterase. Of these, tacrine is not recommended because of its hepatotoxic-
ity, and the other three are about equally effective and equally tolerable;
10 mg/day of donepezil, 6–12 mg/day of rivastigmine, and 16–18 mg/day of
galantamine can be expected to produce, on average, about a three-point im-
provement on the cognitive subscale of the Alzheimer’s Disease Assessment
Scale (Ritchie et al. 2004). Continuation treatment with cholinesterase inhib-
itors slows the progression of Alzheimer’s disease and reduces the likelihood
of nursing home placement. One 36-month follow-up study found that al-
most 80% fewer cholinesterase inhibitor–treated subjects were admitted to
nursing homes compared with untreated subjects (Lopez et al. 2005).
Memantine
Memantine is the first noncholinesterase inhibitor that has been shown, in ran-
domized controlled clinical trials, to be effective in reversing or slowing cogni-
tive and functional decline in Alzheimer’s disease (Areosa et al. 2005). The drug
is an antagonist of the N-methyl-D-aspartate (NMDA)–type glutamate recep-
tor and appears to exert its effects at the cellular level by reducing glutamate-
mediated excitotoxicity, which leads to neuronal injury or death. Unlike the
cholinesterase inhibitors, memantine is effective in patients with moderate to
severe Alzheimer’s disease and seems to exert at least additive effects when com-
bined with cholinesterase inhibitors (Tariot et al. 2004). Improvement in agita-
tion and mood has been observed in several clinical trials, but cognitive and
functional decline in Alzheimer’s disease remains the main indication. The ini-
tial dose is 5 mg/day, which is increased in 5-mg/day increments over 4 weeks
to the final dose of 10 mg twice per day. Side effects are minimal, with dizziness,
confusion, headache, and constipation being most often reported. Memantine
undergoes little metabolism, and adverse drug-drug interactions have not been
reported and are unlikely. Table 5–10 shows the clinical pharmacology of the
cholinesterase inhibitors and memantine.
Other Agents
NSAIDS, hormones, statins, and ginkgo biloba have been studied in patients
with Alzheimer’s disease, and some positive results have been reported, but to
date definitive evidence of the efficacy of any of these agents remains unpub-
lished. Sano et al. (1997) reported that patients with Alzheimer’s disease who
were taking 2,000 IU of vitamin E showed no improvement in cognitive
function but did take significantly longer to require institutionalization than
did those receiving either placebo or 10 mg/day of selegiline. Although this
finding has not been replicated, it has stimulated some clinicians to add high-
dose vitamin E to the treatment regimen of patients with Alzheimer’s disease.
Psychopharmacotherapy for Noncognitive Symptoms of

Agitation
Perhaps the most common and most debilitating symptom complex seen in
patients with Alzheimer’s disease is agitation, a syndrome that occurs in al-
most all patients with Alzheimer’s disease as they progress into the middle and
late stages of illness. Agitation typically presents as restlessness, pacing, irrita-
bility, anger, anxiety and fearfulness, and refusal to accept care, often accom-
panied by persecutory beliefs that may reach delusional severity and verbal or
physical aggressiveness. Agitation is often accompanied by impaired attention
and concentration, elevated heart rate and blood pressure, and tachypnea.
Table 5–10. Clinical pharmacology of agents useful for reducing the signs of dementia
Characteristic Donepezil Rivastigmine Galantamine Memantine
Time to maximal serum 3–5 0.5–2 0.5–1 3–7

concentration (hr)
Absorption affected by food? No Yes Yes No
Serum half-life (hr) 70–80 2a 5–7 60–80
Protein binding (%) 96 40 0–20 45
Metabolism (CYP enzyme) 2D6, 3A4 Nonhepatic 2D6, 3A4 Nonhepatic
Dose (initial/maximal) 5–10 mg/day 1.5–6 mg twice daily 4–12 mg twice daily 5–10 mg twice daily

Mechanism of action Cholinesterase Cholinesterase Cholinesterase NMDA receptor
inhibitor inhibitor inhibitor antagonist
Note. CYP= cytochrome P450; NMDA=N-methyl-D-aspartate.

a
Rivastigmine is a pseudoirreversible acetylcholinesterase inhibitor that has an 8-hour half-life for the inhibition of acetylcholinesterase in the brain.
Source. Adapted from Cummings JL: “Alzheimer’s Disease.” New England Journal of Medicine 351:56–67, 2004. Copyright © 2004 Massachusetts
Medical Society. All rights reserved.
215
Verbalizations range from perseverative expressions of apprehension and fear

to pressured incoherence, screaming, and cursing. Episodes of agitation often
occur during the late afternoon or early evening (“sundowning”).
Before medications are prescribed for agitation, it is important to examine
the patient and his or her physical and social environment to determine what,
if any, unmet needs are contributing to the agitation. Interventions may in-
clude providing optimal levels of sensory stimulation, engaging activities, and
social contact; timely toileting; better communication; and adequate treat-
ment of pain. Behavioral interventions based on an operant conditioning
model and interventions to reduce overstimulation and stress also have been
reported to be effective, but specific guidelines for which intervention is best
for which patient remain to be determined (Cohen-Mansfield 2001).
When nonpharmacological measures have been applied and symptoms
remain, conventional and atypical neuroleptics, benzodiazepines, trazodone,
anticonvulsants (including carbamazepine, valproic acid, and gabapentin), or
lithium may be prescribed. All of these medications have been reported to be
effective, but conventional (Devanand et al. 1998) and atypical (Fujikawa et
al. 2004; Rabinowitz et al. 2004) neuroleptic medications have been the best-
studied and most commonly used agents for agitation, at least until April
2005. At that time, the U.S. Food and Drug Administration (FDA) issued a
public health advisory, citing 17 placebo-controlled trials of olanzapine, ari-
piprazole, risperidone, and quetiapine in elderly patients with dementia who
also had behavior disorders. In 15 of those trials, which included more than
5,106 patients, a 1.6- to 1.7-fold increase in mortality was seen, mainly from
“heart-related events,” including heart failure and sudden death, or infec-
tions, mostly pneumonia. The atypical antipsychotics fall into three drug
classes based on their chemical structure, but because the increase in mortality
was seen with medications in all three chemical classes, the FDA concluded
that the increased mortality was probably related to the common pharmaco-
logical effects of all atypical antipsychotic medications, including those that
had not been systematically studied in the dementia population. Accordingly,
the FDA requested manufacturers of all atypical antipsychotic medications to
add a boxed warning to their drug labeling that describes this risk and that
notes that these drugs are not approved for the treatment of behavior disor-
ders in elderly patients with dementia. The FDA is also considering adding a
warning to the labeling of older antipsychotic medications because limited
data also suggested a similar increase in mortality for these agents. Accord-
ingly, clinicians should consider this risk before recommending antipsychotic
medications for agitation in elderly individuals with dementia. (The FDA ad-
visory is available at http://www.fda.gov/cder/drug/infopage/antipsychotics/
default.htm.)
Typical dosage ranges of neuroleptic medications are 0.5–3 mg/day of
haloperidol, 1–3 mg/day of risperidone, 5–10 mg/day of olanzapine, and 25–
200 mg/day of quetiapine, administered in two or three doses orally or, with
conventional agents, by intramuscular injection. Low-potency, high-dose
conventional agents such as thioridazine are generally avoided because of their
greater anticholinergic potency, which can increase confusion in patients with
Alzheimer’s disease, and their propensity to cause other side effects such as
orthostatic hypotension. High-potency agents are also effective when agita-
tion is accompanied by hallucinations, delusions, belligerent and hostile be-
havior, or physical aggressiveness. In one unreplicated double-blind, random-
assignment study, Sultzer and associates (1997) found that trazodone (50–
250 mg/day) was as effective as haloperidol (1–5 mg/day) for agitation and
somewhat more effective in the subgroup of patients with repetitive, verbally
aggressive, and oppositional behaviors. Street and associates (2000) found
that olanzapine (in dosages of 5 and 10 mg/day) was superior to placebo for
control of agitation or aggression and psychosis in nursing home residents
with Alzheimer’s disease; side effects were limited to somnolence and gait dis-
turbance, and no extrapyramidal or anticholinergic symptoms were seen.
If symptoms of agitation do not respond to neuroleptic therapy at dosages
low enough to avoid significant side effects, switching to trazodone or aug-
menting with lorazepam, 0.5–1 mg administered orally or by intramuscular
injection, may be effective. A typical daily regimen would include a standing
order for 2 mg of haloperidol or risperidone orally at bedtime and either
1) 0.5 mg of lorazepam orally every 4–6 hours as a standing order or as
needed or 2) 25–50 mg of trazodone orally every 4–6 hours as a standing or-
der or as needed. Refractory symptoms may require treatment with neurolep-
tics and trazodone.
Several rating scales, including the Behavior Pathology in Alzheimer’s Dis-
ease Rating Scale (BEHAVE-AD; Reisberg et al. 1987), the Cohen-Mansfield
Agitation Inventory (Cohen-Mansfield et al. 1989), and the Agitated Behavior
in Dementia scale (Logsdon et al. 1999), are available to track treatment effect.
Anticonvulsants such as valproic acid also have a role in the pharmacological

management of behavioral disturbance in patients with Alzheimer’s disease
(Sival et al. 2004) and may be particularly effective in patients with a history
of mood instability or those with prominent mood instability as a feature of
their agitation.
Finally, evidence indicates that cholinesterase inhibitors such as donepezil
and rivastigmine, in addition to improving cognitive function in Alzheimer’s
disease, have salutary effects on noncognitive symptoms, including agitation,
hallucinations, delusions, disinhibition, and apathy (Aupperle et al. 2004;
Holmes et al. 2004). Table 5–11 shows the clinical pharmacology of agents
useful for the control of symptoms and signs of agitation.
Anxiety
Patients with Alzheimer’s disease are also susceptible to anxiety in various
forms and degrees of severity. Although treatment with anxiolytics is generally
guided by the same principles that apply to elderly patients without dementia
(see Chapter 7, “Anxiety Disorders and Late-Onset Psychosis”), patients with
Alzheimer’s disease may be unable to articulate subjective feelings of appre-
hension, psychomotor tension, or fear, and the clinician may be forced to rely
on more objective signs. In this regard, mild agitation as described earlier can
reflect an anxiety state and may respond to anxiolytics alone.
Depression
Although authorities disagree on the prevalence of clinical depressive disor-
ders in patients with Alzheimer’s disease, such disorders do occur and can be
quite disabling, often leading to increased cognitive impairment (a syndrome
that has been termed pseudodementia). Tricyclics and selective serotonin re-
uptake inhibitors have been studied in this regard, with mixed results (Katona
et al. 1998; Lyketsos et al. 2000a; Taragano et al. 1997). In general, the prin-
ciples that guide treatment of depression in elderly patients without dementia
apply (see Chapter 4, “Mood Disorders—Treatment”), with the following
modifications:
• Patients with Alzheimer’s disease, by virtue of cholinergic system disrup-

tion, are particularly susceptible to adverse reactions ranging from subtle
worsening of cognitive function to frank delirium while taking centrally

acting anticholinergic agents. Accordingly, tricyclic antidepressants and
other anticholinergic agents should be avoided when possible, in favor of
selective serotonin reuptake inhibitors and the other nontricyclic antide-
pressants.
• Because patients with Alzheimer’s disease may have impaired ability to
articulate subjective feelings of sadness, hopelessness, helplessness, or
worthlessness, the clinician often must rely more on neurovegetative signs
and nonverbal expression of mood as target symptoms for treatment. The
latter may include refusal to eat, crying spells, facial expressions of sadness
or pain, unexplained episodes of agitation or hostility, and increased con-
fusion.
• Patients with Alzheimer’s disease also may not be able to describe subjec-
tive side effects of medications, such as postural light-headedness or diz-
ziness, so routine measurements of orthostatic blood pressure and careful
assessment of gait and balance may be more necessary than in the elderly
patient without dementia.
Mood Instability, Insomnia, Apathy

Lithium, valproic acid, and other mood-stabilizing agents may be prescribed for
patients with Alzheimer’s disease who have concomitant bipolar disorder or its
variants, following the considerations listed above. Similarly, benzodiazepine
and nonbenzodiazepine hypnotic agents are prescribed for patients with Alzhei-
mer’s disease, as for elderly persons without dementia. The common practice of
prescribing diphenhydramine or other antihistamines as hypnotics is particu-
larly inadvisable for patients with Alzheimer’s disease because these agents have
significant anticholinergic potency and can cause increased cognitive impair-
ment. Psychostimulants such as methylphenidate and modafinil have a minor
role in treatment of Alzheimer’s disease. Although it has been repeatedly docu-
mented that these agents do not improve cognitive function, they can be effec-
tive for apathy and social withdrawal and are occasionally useful to reverse
sedative side effects of other agents.
Table 5–11. Clinical pharmacology of medications for agitation with and without psychosis

Dosage Side effects and
Medication Indications (mg/day) adverse reactions Special considerationsa
Haloperidol Agitation, psychosis 0.5–2.0 EPS, tardive dyskinesia, akathisia,

drowsiness
Risperidone Agitation, psychosis 0.5–2.0 EPS, tardive dyskinesia, akathisia, May increase risk of stroke in
drowsiness, metabolic syndrome patients with cerebrovascular
disease
Olanzapine Agitation, psychosis 2.5–10 Drowsiness, weight gain, metabolic May increase risk of stroke in
syndrome patients with cerebrovascular
disease
Quetiapine Agitation, psychosis 25–200 Drowsiness, weight gain, metabolic
syndrome
Aripiprazole Agitation, psychosis 5–30 Drowsiness, weight gain, metabolic
syndrome
Trazodone Agitation 25–200 Drowsiness, orthostatic hypotension
Valproate Agitation, mood lability 250–1,500 Drowsiness, ataxia
Note. EPS=extrapyramidal side effects.

a
All (except trazodone and valproate) may increase risk of death from multiple causes.
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Resources for Dementia Caregivers

Alzheimer’s Association: (800) 272-3900, http://www.alz.org
American Association of Retired Persons (AARP): http://www.aarp.org (information
about the Family and Medical Leave Act)
Kaplan M, Hoffman S (eds): Behaviors in Dementia: Best Practices for Successful
Management. Baltimore, MD, Health Professions Press, 1998
Mace NL, Rabins PV (eds): The 36-Hour Day, 3rd Edition. Baltimore, MD, Johns
Hopkins University Press, 1999
National Institutes of Health Clinical Trials: http://www.clinicaltrials.gov (clinical trials
that are recruiting patients with Alzheimer’s disease)
U.S. Department of Health and Human Services, Administration on Aging: (800)
677-1116, http://www.aoa.gov (click on “Elders and Families” for help with
locating services and resources for older adults)
6
Other Dementias and Delirium
Frontotemporal Dementia
Frontotemporal dementia is a term used to describe a group of disorders that
share a common pattern of relatively focal degeneration of the frontal and
temporal lobes of the brain. Classic Pick’s disease, primary progressive apha-
sia, and several other histopathologically distinct conditions are the main con-
tributors to this category.
Epidemiology
Because of the histopathological heterogeneity of this syndrome (see “Pathol-
ogy” below), and the overlap of its clinical features with those of Alzheimer’s
disease and vascular dementia, it is difficult to estimate its prevalence. One
Swedish study (Andreasen et al. 1999) found a prevalence of 3.2% in a clini-
cally diagnosed sample of 619 patients referred for diagnostic evaluation
(compared with 36.9% with Alzheimer’s disease), whereas Gustafson and col-
leagues (1992) estimated the prevalence as close to 10%. Ratnavalli and col-
leagues (2002) analyzed records from a university hospital in Cambridge,
England, and found that frontotemporal dementia and Alzheimer’s disease
had the same prevalence (15 per 100,000) in patients ages 45–64; the average
age at onset of the frontotemporal dementia was 52.2 years.
Diagnostic Criteria
Consensus criteria for diagnosing frontotemporal dementia were published in
1998 (Neary et al. 1998) and are presented in Table 6–1.
229
Table 6–1. Clinical diagnostic features of frontotemporal

dementia
Core diagnostic features
Insidious onset and gradual progression
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight
Supportive diagnostic features
Behavior disorder
Decline in personal hygiene and grooming
Mental rigidity and inflexibility
Distractibility and impersistence
Hyperorality and dietary changes
Perseverative and stereotyped behavior
Utilization behavior
Speech and language
Altered speech output
Aspontaneity and economy of speech
Press of speech
Stereotypy of speech
Echolalia
Perseveration
Mutism
Physical signs
Primitive reflexes (e.g., grasp, snout, glabellar)
Incontinence
Akinesia, rigidity, and tremor
Low and labile blood pressure
Investigations
Neuropsychology: significant impairment on frontal lobe tests in the
absence of severe amnesia, aphasia, or perceptuospatial disorder
Electroencephalography: conventional electroencephalogram findings
are normal despite clinically evident dementia
Other Dementias and Delirium 231
Table 6–1. Clinical diagnostic features of frontotemporal

dementia (continued)
Supportive diagnostic features (continued)
Investigations (continued)
Brain imaging (structural and/or functional): predominant frontal and/or
anterior temporal abnormality
Source. Adapted from Neary et al. 1998.
History, Clinical Presentation, and Mental Status

Examination
The typical age at onset of frontotemporal dementia is in the 50s and 60s, and
a family history of dementia is present in about half of cases, with a dominant
pattern of inheritance found in the majority (Chow et al. 1999). Some au-
thorities subdivide frontotemporal dementia into three clinical subsyndromes
based on its initial presentation: 1) frontal variant frontotemporal dementia
(often called dementia of frontal type), 2) semantic dementia, and 3) progres-
sive nonfluent aphasia. In the frontal variant, the main presenting feature is
progressive personality change, with disinhibition, loss of empathy, change in
eating patterns, ritualized or stereotypical behavior, and apathy (Bozeat et al.
2000). Semantic dementia is characterized by progressive loss of knowledge
of people, objects, facts, and word meanings and is associated with primarily
temporal lobe pathology. Progressive nonfluent aphasia is associated with pri-
marily frontal (perisylvian) pathology, presents with deficits in the phonolog-
ical and syntactic components of language (Grossman 2002), and may
progress to corticobasilar degeneration (Gorno-Tempini et al. 2004). A recent
longitudinal study (Seeley et al. 2005) found that after an average of 3 years,
patients who initially presented with the semantic (left temporal) variant of
frontotemporal dementia also developed the symptoms of right frontotempo-
ral deficit (especially emotional flatness, irritability, and disruption of physi-
ological drives such as sleep and appetite), and those with initially prominent
behavioral symptoms developed semantic language deficits. Disinhibition,
compulsions, altered food preferences, and weight gain emerged in both
groups later in the disease, about 5–7 years after onset.
Screening Instruments and Rating Scales

Most brief mental status examinations do not assess frontal executive func-
tions, and as a result, individuals with frontotemporal dementia may score in
the normal range on brief examinations in the early to middle stages of dis-
ease. Several short batteries have been developed to help clinicians test for
frontal lobe changes, including the Executive Interview (Royall et al. 1992)
and the Frontal Assessment Battery (FAB; Dubois et al. 2000). Both measures
take about 10 minutes to administer and cover several different aspects of be-
havior, cognition, or motor function affected by frontal lobe syndromes. The
FAB differentiates better between frontotemporal dementia and Alzheimer’s
disease than does the Mini-Mental State Examination (MMSE) (Slachevsky
et al. 2004), and it is now used frequently in clinical research (e.g., Mendez
et al. 2005). The Executive Interview correlates well with neuropsychological
measures of executive function and is sensitive to differences in everyday
functional level for older adults in residential care (Royall et al. 1992) and re-
tirement facilities (Royall et al. 2005). If the referral question concerns differ-
entiation between frontotemporal dementia and Alzheimer’s disease, these
brief screens are a good starting point; however, brief screening is less likely to
differentiate frontotemporal dementia from other syndromes that preferen-
tially affect frontal executive function (e.g., dementia with Lewy bodies,
schizophrenia, or major depression). In such cases, referral for neuropsycho-
logical assessment should be considered to document impairments and to
differentiate changes due to dementia from affective illness or personality dis-
order.
Informant rating scales also may help to ensure that a thorough picture of
frontal deficits in everyday settings is obtained. The Frontal Systems Behavior
Scale (Grace and Malloy 2001) provides standardized ratings of apathy, exec-
utive skills, and disinhibition and has parallel forms for the patient and infor-
mant that can be useful for assessing patients’ self-awareness of behavior
changes. The Frontal Systems Behavior Scale has been shown to discriminate
dementias with prominent frontal system neuropathology from other demen-
tias and also has been used with psychiatric patients. The standardization
sample for this measure included participants up to age 95 years, and norms
are stratified by age, education, and gender. The Frontal Behavioral Inventory
(Kertesz et al. 2000) is completed by a trained professional on the basis of a
structured caregiver interview. Items for this scale were based on behaviors de-
scribed in diagnostic consensus reports (e.g., Neary et al. 1998) for fronto-
temporal dementia. The Frontal Behavioral Inventory has good reliability
and appears effective in discriminating clearly diagnosed frontotemporal de-
mentia from Alzheimer’s disease or vascular dementia. However, norms for
clinical use are lacking. The Neuropsychiatric Inventory (NPI; see Chapter 5,
“Dementia and Alzheimer’s Disease,” and Appendix) is another behavior rat-
ing scale completed by professionals on the basis of a caregiver interview. It
taps several behaviors that are often affected in frontotemporal dementia and
has been used in clinical trials. A caregiver-completed form of the NPI has
been developed (Kaufer et al. 2000), but data are limited on the clinical use-
fulness of this version.
The symptoms of frontotemporal dementia, especially the frontal variant,
are often very distressing to family members, and education is needed to help
with understanding the avolitional nature of specific behavior changes and
with developing management strategies. A systematic survey of affected be-
haviors, whether based on direct informant ratings or interviews, can provide
a good starting point for tailoring interventions for caregivers.
Physical and Neurological Examination

As shown in Table 6–1, grasp, snout, and glabellar reflexes may be present,
and some patients will develop parkinsonian signs and symptoms or motor
neuron abnormalities in the later stages.
On neuropsychological examination, frontotemporal dementias can be dis-
tinguished in early stages from dementia due to Alzheimer’s disease by the rel-
ative salience of executive function deficits as opposed to memory disorder or
by the emergence of progressive alterations in speech (e.g., dysfluency, stereo-
typy) before notable memory deficits emerge. Neuropsychological tests sensi-
tive to frontal executive dysfunction include motor programming tasks,
cognitive speed and flexibility measures (e.g., the Trail Making Test), and rea-
soning tasks (e.g., the Similarities subtest of the Wechsler Adult Intelligence
Scale—Third Edition), as well as naming and verbal fluency tests (see Table
5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for test descriptions).
The heterogeneity that has been noted in frontotemporal dementia is also
apparent on testing, with some affected persons having striking changes in

personality and social behavior early on, but preserved communication skills,
and others showing prominent language deficits with relative preservation of
personality. The Delis-Kaplan Executive Function System (Delis et al. 2001)
provides representative norms for interpreting several commonly used execu-
tive function tests, as well as detailed information on qualitative features of
performance that may be important diagnostically.
Depending on the underlying pathology, frontal and temporal hypoperfusion
(on single photon emission computed tomography), reduced glucose metab-
olism (on positron emission tomography with fluorodeoxyglucose), and atro-
phy (on computed tomography or magnetic resonance imaging) may be seen
in frontotemporal dementia.
Differential Diagnosis
The other degenerative dementias (Alzheimer’s disease and dementia with
Lewy bodies); vascular dementia; the dementias associated with Huntington’s
disease, Parkinson’s disease, Creutzfeldt-Jakob disease, human immunodefi-
ciency virus (HIV) infection, and head trauma; and those associated with
other general medical conditions all must be ruled out before a diagnosis of
frontotemporal dementia is made. Because of the lack of differentiating phys-
ical signs, and the tendency for Alzheimer’s disease to include signs and symp-
toms of frontal lobe involvement, the most challenging distinction is between
frontotemporal dementia and Alzheimer’s disease. Table 6–2 summarizes the
main differentiating features of these two conditions. Knopman et al. (2005)
reviewed 433 cases that went to autopsy and found that frontotemporal de-
mentia was correctly identified on the basis of clinical and laboratory findings
in 29 of 34 autopsy-verified cases. This finding represents 85% sensitivity; the
authors also reported 99% specificity.
Pathology
The typical gross pathological finding is of frontal and anterotemporal atrophy.
Microscopic findings have been subdivided according to the profile of immu-
nohistochemical staining and the pattern of intracellular inclusions, as follows:
1. Tau-positive pathology, including classic argyrophilic, tau-positive, intra-

neuronal Pick bodies (Pick’s disease);
2. Tau gene mutations (FTDP17) and diffuse tau-positive neuronal and
astrocytic immunoreactivity;
3. Tau-positive astrocytic plaques and ballooned achromatic neurons (cor-
ticobasal degeneration); and
4. Tau-positive argyrophilic grain disease.
The second and third subdivisions above include cases with tau-negative,
ubiquitin-positive inclusions in the dentate gyrus and in the brain-stem mo-
tor nuclei (frontotemporal dementia with motor neuron inclusions) and de-
mentia lacking distinctive histology (Hodges et al. 2004).
Treatment
There is no specific treatment for the personality or cognitive changes seen in
the frontotemporal dementias, but several aspects of disturbed behavior have
been reported to respond to psychopharmacological treatment. Trazodone
improved symptoms of irritability, agitation, depression, and eating disorders
in one randomized, double-blind, placebo-controlled crossover study (Lebert
et al. 2004), and similar results have been observed in open-label studies with
moclobemide (Adler et al. 2003), rivastigmine (Moretti et al. 2004), and par-
oxetine (Moretti et al. 2003). However, a double-blind, placebo-controlled
crossover study with paroxetine resulted in worsening cognition and no im-
provement in behavior (Deakin et al. 2004), suggesting that open-label treat-
ment studies in frontotemporal dementia may be misleading.
Dementia With Lewy Bodies

Dementia with Lewy bodies (McKeith et al. 1996) is a progressive, degener-
ative dementing condition with clinical and pathological features that overlap
with those of Alzheimer’s disease and Parkinson’s disease. Its precise nosolog-
ical status remains controversial because some authorities regard it as a variant
of Alzheimer’s disease and others consider it a clearly distinct condition. This
debate has led to the use of various terms for this condition, including senile
dementia of the Lewy body type and diffuse Lewy body disease.
Table 6–2. Differentiation of Alzheimer’s disease from

frontotemporal dementia
Alzheimer’s disease Frontotemporal dementia
Symptom
Behavior Socially correct Early disinhibition
Affect Normal Remote, bizarre
Apathy Mild Severe
Delusions Simple Bizarre
Compulsions Mild Severe
Eating Weight loss Weight gain
Neuropsychological test performance
Drawing Impaired Spared
Memory Impaired Variable
Executive function Impaired Severely impaired
Generation Impaired Severely impaired
Anomia Lexical Semantic (often)
Neuropathology
Plaques Yes No
Tangles Yes No (except for familial
tauopathy)
Gliosis Proportional to neuronal Out of proportion to
loss neuronal loss
Abnormal genes Amyloid precursor protein,
presenilin 1 and 2;
apolipoprotein ε4;
tau mutations
Neurochemistry
Cholinergic deficit Presynaptic cholinergic Postsynaptic cholinergic;
and serotonergic presynaptic and
postsynaptic serotonergic
Positron emission Temporoparietal Frontotemporal
tomography hypometabolism hypometabolism
Source. Adapted from Miller BL, Gustavson A: “Alzheimer’s Disease and Frontotemporal De-
mentia,” in American Psychiatric Press Textbook of Geriatric Neuropsychiatry, 2nd Edition. Edited
by Coffey CE, Cummings JL. Washington, DC, American Psychiatric Press, 2000, p. 521. Copy-
right © 2000, American Psychiatric Press. Used with permission.
Epidemiology
The prevalence and incidence of dementia with Lewy bodies are not well es-
tablished, but autopsy series have found it to account for 15%–36% of cases
of dementia (Hansen et al. 1990; Holmes et al. 1999), which would make it
the second most common cause of dementia, after Alzheimer’s disease.
Diagnostic Criteria
Consensus criteria published originally by McKeith et al. (1996) and recently
revised (McKeith et al. 2005) require dementia and two of the following three
core features to make a diagnosis of probable dementia with Lewy bodies:
“fluctuating cognition with pronounced variations in attention and alertness;
recurrent visual hallucinations that are typically well formed and detailed; and
spontaneous motor features of parkinsonism” (McKeith et al. 2005, p. 1864).
If one or more of the following suggestive features are present, a diagnosis
of probable dementia with Lewy bodies can be made in the presence of only
one core feature: “REM [rapid eye movement] sleep behavior disorder [“vivid
and often frightening dreams during REM sleep, but without muscle atonia,”
McKeith et al. 2005, p. 1866]; severe neuroleptic sensitivity; and low dopa-
mine transporter uptake in basal ganglia as demonstrated by [single photon
emission computed tomography] SPECT or [positron emission tomography]
PET imaging” (McKeith et al. 2005, p. 1864).
Supportive features include “repeated falls and syncope; transient unex-
plained loss of consciousness; depression; systematized delusions; hallucina-
tions in other modalities; relative preservation of medial temporal lobe
structures on computed tomography/magnetic resonance imaging scan; gen-
eralized low uptake on SPECT/PET perfusion scan with reduced occipital ac-
tivity; abnormal (low uptake) MIBG (metaiodobenzyl guanidine—a measure
of postganglionic sympathetic cardiac innervation) myocardial scintigraphy;
and prominent slow wave activity on electroencephalogram with temporal
lobe transient sharp waves” (McKeith et al. 2005, p. 1864).
The diagnosis of dementia with Lewy bodies is less likely if “cerebrovascular
disease evident as focal neurological signs or on brain imaging is present; in the
presence of any other physical illness or brain disorder sufficient to account in
part or in total for the clinical picture; and if parkinsonism only appears for the
first time at a stage of severe dementia” (McKeith et al. 2005, p. 1864).
Although the consensus criteria have enjoyed widespread acceptance,

Serby and Samuels (2001) reexamined their usefulness via a critical analysis
of 242 published cases of dementia with Lewy bodies and found visual hallu-
cinations and fluctuating cognition to be of very limited value. The authors
suggested that these features often may be a result of treatment rather than
“core” features of the disease and concluded that “greater caution should be
used in the establishment of a set of diagnostic criteria for DLB [dementia
with Lewy bodies]. The presence of parkinsonism and, perhaps, its co-occur-
rence with dementia appear to be the most reliable indicators of the presence
of DLB” (p. 215).
History
The history of dementia with Lewy bodies is typically of a gradual, progres-
sive decline in intellectual function that is almost always eventually accompa-
nied by parkinsonism. Although marked day-to-day fluctuations in cognitive
function and well-formed, silent visual hallucinations that typically appear as
animals, objects, or people that the patient insists are real may turn out to be
accidental features of the illness, their occurrence should be considered at least
supportive, if not diagnostic. The history is likely to include repeated falls,
syncope, transient loss of consciousness, neuroleptic sensitivity, systematized
delusions, and hallucinations in other modalities, as well as extrapyramidal re-
actions to conventional neuroleptics (severe) and atypical neuroleptics (severe
in comparison to patients with other conditions), all of which are also re-
garded as supportive of the diagnosis of dementia with Lewy bodies. REM
sleep behavior disorder also may be present early in the disease (Ferman et al.
2002).
Clinical Presentation and Mental Status Examination

The clinical presentation is of a dementia with intellectual changes that gen-
erally parallel those of Alzheimer’s disease, except the early memory impair-
ment is more likely to represent a retrieval deficit than the impairment in new
learning typically seen in Alzheimer’s disease. Deficits in attentional processes
are also common in dementia with Lewy bodies, as are deficits in executive
functions.

Physical and neurological examination in dementia with Lewy bodies is likely
to detect bradykinesia and rigidity, particularly in the later stages of illness,
but parkinsonian tremor may be absent. Evidence of stroke or other physical
conditions that could account for the clinical features should be considered as
evidence against a diagnosis of dementia with Lewy bodies.
Cognitive profiles of patients with dementia with Lewy bodies overlap with
those of Alzheimer’s disease patients in that both show deficits in multiple areas,
including memory dysfunction. Compared with patients with uncomplicated
Alzheimer’s disease, however, individuals with dementia with Lewy bodies may
have disproportionate problems with attention and working memory, visuoper-
ceptual processing, and executive function. In dementia with Lewy bodies, low
scores are likely to be seen on nearly all types of attention tasks, whereas simple
attention (e.g., forward digit span) is usually preserved in Alzheimer’s disease.
Similarly, persons with dementia with Lewy bodies often have more difficulty
than do patients with Alzheimer’s disease on relatively simple visuoperceptual
tasks such as recognizing fragmented letters or extracting meaning from pic-
tures (Calderon et al. 2001). By contrast, delayed recall tends to be better pre-
served in dementia with Lewy bodies than in Alzheimer’s disease, especially if
the newly learned information is organized in a natural way (e.g., stories) (Cal-
deron et al. 2001); there may also be greater benefit from cues and recognition
testing formats. Typically, more psychomotor slowing occurs early in the course
of dementia with Lewy bodies, and patients have greater difficulty with motor
programming and executive functions such as shifting from one thought or ac-
tion to another.
A recent study comparing autopsy-verified cases of Alzheimer’s disease,
dementia with Lewy bodies, and combined Alzheimer’s disease and dementia
with Lewy bodies (Kraybill et al. 2005) provided further support that neuro-
psychological testing may help in diagnostic differentiation. Participants in
this study were tested early in the course of illness (about 1 year after the onset
of memory problems), and at that point, no significant differences were seen
between diagnostic groups on mental status examinations (either the MMSE
or the Dementia Rating Scale; see Table 5–1). However, individuals later
found to have pure Alzheimer’s disease or combined Alzheimer’s disease and

dementia with Lewy bodies performed worse on verbal memory measures
and confrontation naming than did those with pure dementia with Lewy
bodies; by contrast, patients with dementia with Lewy bodies had more im-
pairment at baseline on a measure of psychomotor speed and executive func-
tion (Trail Making Test) and on an attention test (digit span) (see Table 5–5
for descriptions of these measures). Interestingly, no differences were observed
on brief screening measures of attention and executive function (Dementia
Rating Scale subscales), suggesting that referral for detailed neuropsychologi-
cal testing may be needed to improve antemortem diagnostic accuracy for de-
mentia with Lewy bodies.
The differential diagnosis of dementia with Lewy bodies includes essentially
all of the dementing diseases, including Alzheimer’s disease, frontotemporal
dementia, vascular dementia, Parkinson’s disease and Alzheimer’s disease, and
Parkinson’s disease with dementia.
Pathology and Pathogenesis

The micropathology of dementia with Lewy bodies involves extensive cortical
neuritic plaques, as are seen in Alzheimer’s disease, with relatively few neu-
rofibrillary tangles. Lewy bodies (intracytoplasmic spherical, eosinophilic
neuronal inclusion bodies that can also be visualized via antiubiquitin immu-
nocytochemical detection techniques [McKeith et al. 1996]) are widespread
in the brain stem, subcortical nuclei, limbic cortex, and neocortex. Neuro-
chemical analysis of neocortical brain tissue indicates loss of cholinergic
markers (i.e., choline acetyltransferase and acetylcholinesterase) of a magni-
tude even greater than that reported in Alzheimer’s disease.
Treatment
Because of the relatively severe loss of cholinergic innervation found in demen-
tia with Lewy bodies, cholinesterase inhibitors such as donepezil and rivastig-
mine have been studied in this condition. A double-blind, placebo-controlled,
double-crossover study of just seven subjects found donepezil to be statistically
significantly superior to placebo, as measured by the MMSE and the Alzhei-
mer’s Disease Assessment Scale–cognitive subscale, after 4 weeks of treatment

(Beversdorf et al. 2004). In another double-blind, placebo-controlled, random-
assignment study (Wesnes et al. 2002), subjects taking rivastigmine (6–12 mg/
day) had significantly improved attention, working memory, and episodic sec-
ondary memory, as assessed by a computerized test battery, compared with
those taking placebo. Most treatment effects disappeared 3 weeks after rivastig-
mine was discontinued.
Treatment of agitation or psychosis in dementia with Lewy bodies is com-
plicated by severe extrapyramidal reactions to conventional neuroleptics, and
even the atypical agents risperidone, olanzapine, and clozapine have been re-
ported to cause significant extrapyramidal symptoms in dementia with Lewy
bodies. Until a “class effect” is established, other atypical agents such as
quetiapine, ziprasidone, and aripiprazole may therefore be preferable for
symptoms of agitation and psychosis that remain after administration of cho-
linesterase inhibitors.
Vascular Dementia
Epidemiology
The prevalence of vascular dementia is difficult to estimate because no gener-
ally accepted and validated neuropathological criteria have been established
to date, and this has impeded definitive validation of clinical diagnostic crite-
ria for vascular dementia (Jellinger 2005). Still, community-based studies
suggest that 1) the prevalence of clinical vascular dementia is age dependent,
with prevalence rates doubling every 5 years; 2) the frequency of vascular de-
mentia is higher in men; and 3) the prevalence differs substantially from na-
tion to nation. Overall, the prevalence of vascular dementia ranges from 2.2%
in 70- to 79-year-old women to 16.3% in men older than 80 (Leys et al.
1998).
Diagnostic Criteria
The nosological status of vascular dementia has been called into question by au-
topsy studies indicating that the underlying neuropathology in clinical vascular
dementia is commonly a “mixture” of vascular lesions and other degenerative
conditions, usually Alzheimer’s disease. A report by Hulette and colleagues
(1997) indicated that only 6 of nearly 2,000 brains of individuals with demen-
tia that were surveyed by pathologists had “pure” vascular pathology. If this fig-
ure is at all representative, clinical vascular dementia should be thought of as
a “vascular complication” superimposed on another dementing illness in many,
if not most, cases. This view was supported by Chui (2005), who reviewed the
status of cerebrovascular brain injury (CVBI) in relation to dementia and
stated, “An emerging database suggests that CVBI contributes significantly to
mild cognitive impairment and can precipitate the appearance of dementia in
early stages of AD [Alzheimer’s disease] pathology. However, the effects of
CVBI may become submerged once AD-pathology arrives at the isocortical
stages” (p. 51). Korczyn (2005) came to a similar conclusion, stating that
most patients diagnosed as VaD [vascular dementia] actually have evidence of

hippocampal atrophy and cortical cholinergic deficiency, both previously
regarded as markers of AD [Alzheimer’s disease]. Demented patients with
vascular brain disease frequently have some degree of amyloid deposits and
neurofibrillary changes, which, although possibly insufficient to fulfill the
arbitrary criteria set for the diagnosis of AD, may nevertheless contribute to
the cognitive changes. Like the AD changes, the vascular damage may accu-
mulate slowly and impair neuronal metabolism and function, eventually
causing neuronal death. (p. 5)
The DSM-IV-TR (American Psychiatric Association 2000) criteria for

vascular dementia are summarized in Table 6–3, but other criteria sets have
been proposed that offer different profiles of specificity and sensitivity (Wet-
terling et al. 1996). A rating scale (Rosen et al. 1980) (Table 6–4) designed to
quantify the probability of underlying infarctions in the patient with demen-
tia has been published on the basis of the clinical signs and symptoms de-
scribed in the following subsections.
History
The history of the current illness in vascular dementia is classically one of a
more abrupt, stepwise course of cognitive impairment than the more gradual
onset and decline typical of “pure” Alzheimer’s disease and other degenerative
dementias. Risk factors identified by the history in vascular dementia are
those associated with stroke—that is, arterial hypertension, atherosclerotic
disease, low education level, alcohol abuse, and heart disease.
Table 6–3. Summary of DSM-IV-TR diagnostic criteria for vascular

dementia
A. The development of multiple cognitive deficits manifested by both
(1) memory impairment
(2) one (or more) of the following cognitive disturbances:
(a) aphasia
(b) apraxia
(c) agnosia
(d) disturbance in executive functioning
B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment
in social or occupational functioning and represent a significant decline from a
previous level of functioning.
C. Focal neurological signs and symptoms or laboratory evidence indicative of
cerebrovascular disease that are judged to be etiologically related to the
disturbance.
D. The deficits do not occur exclusively during the course of a delirium.
Clinical Presentation and Mental Status Examination

Vascular dementia is clinically very similar to other dementias, although certain
features such as relative preservation of personality and insight, depressed mood,
emotional lability, somatic complaints, and “patchiness” of cognitive deficits on
mental status examination are reported to be more common in vascular demen-
tia than in other types of dementia. “Patchiness” refers to the phenomenon of rel-
atively well-preserved islands of function concurrent with relatively deteriorated
areas of function (e.g., relatively well-preserved memory with severe disturbance
of language and praxis, or relatively severe memory impairment with relative
preservation of calculating ability and capacity for abstract thought).

Patients with vascular dementia may have focal neurological signs associated
with ischemic damage to motor cortex and descending tracts, such as exagger-
ated deep tendon reflexes or focal weakness or rigidity, or signs associated with
more global cortical and subcortical damage, such as gait abnormalities,
Table 6–4. Clinical features of the Modified Ischemic Score

Feature Point value
Abrupt onset 2
Stepwise deterioration 1
Somatic complaints 1
Emotional incontinence 1
History or presence of hypertension 1
History of strokes 2
Focal neurological symptoms 2
Focal neurological signs 2
Note. A score of 4 or more is consistent with vascular dementia.
Source. Adapted from Rosen et al. 1980.
dysarthria, impaired gag reflex, extensor plantar reflex, and signs of “frontal re-
lease” such as grasp or snout reflex. Evidence of systemic atherosclerosis (e.g.,
bruits) and signs of poor peripheral circulation (e.g., diminished pulses, atro-
phic skin changes) also may increase the probability that dementia is at least
partly of vascular origin. Physical and neurological examination may show ab-
normal findings associated with Parkinson’s disease (tremor, cogwheel rigidity,
and akinesia), Huntington’s disease (choreoathetoid movements), head trauma
(motor or sensory deficits), HIV infection (tremor, ataxia, atonia and hyperre-
flexia, frontal release signs), or Creutzfeldt-Jakob disease (ataxia, myoclonus).
Neuropsychological test findings in vascular dementia vary with the nature and
severity of cerebrovascular illness. For patients who have had single or multiple
large infarcts, deficits commensurate with the location and extent of infarction
should be expected. For those whose cerebrovascular impairment is limited to
lacunar infarcts or who have extensive deep white matter disease, deficits are
more consistent with subcortical dementia, with impairments expected on tests
of psychomotor speed and dexterity, frontal executive functions (e.g., difficul-
ties with divided attention, attentional shifting, working memory, or behavioral
planning and sequencing), and motor aspects of speech (e.g., dysarthria or re-
duced verbal output may be present) (Roman et al. 1993). Subtle frontal-sub-
cortical deficits may precede clinically significant dementia in patients with
deep white matter disease (leukoaraiosis) or lacunar infarcts, and abrupt change
in mood and personality, with or without clear cognitive impairment, also may
be observed in vascular dementia. A high rate of intertest scatter is not specific
to vascular dementia and cannot be used to identify this condition or to differ-
entiate it from Alzheimer’s disease or other dementias.
Laboratory evaluation generally begins with a selected standardized battery of
tests with relatively high sensitivity and low specificity, as presented in Chapter 5
(“Dementia and Alzheimer’s Disease”; Table 5–4). As indicated in Table 6–3, to
establish a diagnosis of vascular dementia in the absence of neurological signs and
symptoms, laboratory evidence of cerebrovascular disease is required. Computed
tomographic or magnetic resonance brain imaging that shows brain infarction is
sufficient, if the number and location of infarcts are judged to account for the ob-
served cognitive deficits.
As is true of all of the dementing illnesses, the differential diagnosis of vascular
dementia includes Alzheimer’s disease; frontotemporal dementia; dementia
with Lewy bodies; the dementias associated with HIV disease, head trauma,
Parkinson’s disease, Huntington’s disease, and Creutzfeldt-Jakob disease; de-
mentia due to other medical conditions, such as brain tumor, normal-pressure
hydrocephalus, and hypothyroidism; delirium; and functional disorders (see
Table 5–6 in Chapter 5, “Dementia and Alzheimer’s Disease”). As discussed
earlier, the history, clinical presentation, mental status examination, physical
and neurological examination, and laboratory evaluation, including neuropsy-
chological tests, have been considered to be adequate to differentiate vascular
dementia from other dementing illnesses (which are discussed in detail below),
but some studies have cast doubt on this claim. Reed et al. (2004) studied 18
individuals with autopsy-defined cerebrovascular disease and found that
clinical features were quite variable; only 40% of cases with high CVD [cere-
brovascular disease] levels had elevated Hachinski Ischemia Scale scores and
neither abrupt onset nor stepwise progression was found in most high CVD
cases, even when AD [Alzheimer’s disease] changes were essentially absent.
The presence of dementia was predictably related to the level of neurofibril-
lary pathology, but was not related to the severity of CVD. (p. 63)
Nonetheless, delirium is generally distinguishable from vascular dementia

in that delirium is characterized by a much more acute onset and more rapid
progression than vascular dementia, and patients with delirium have a dis-
turbance in consciousness that is not seen in patients with uncomplicated
vascular dementia. However, the diagnostic picture can be clouded in two sit-
uations: 1) when vascular dementia and true delirium occur simultaneously
and 2) during an episode of acute agitation (e.g., “sundowning”) of the type
to which patients with vascular dementia are prone, particularly in the early
evening. Agitation, which is usually a self-limiting, transient state, may have
many of the features of delirium without the implications of deranged phys-
iology and poor prognosis characteristic of true delirium. Accurate diagnosis
of vascular dementia in both cases depends on reevaluation when signs or
symptoms of delirium or acute agitation have cleared, allowing the underly-
ing dementia to be characterized. As described earlier, several functional ill-
nesses can also mimic dementia of any type, including vascular dementia.
Generally, these illnesses are identifiable by the rapid onset and progression of
symptoms and the atypical overall clinical picture (i.e., absence of the neuro-
logical signs and symptoms and risk factors for vascular dementia) seen in the
functional disorders.
Pathogenesis
Vascular dementia is caused by varying combinations of vascular insults to the
brain, including arterial territory infarcts, distal field (watershed/borderzone)
infarcts, small and medium-sized lesions mainly in functionally important
brain areas, lacunar infarcts and scars, white matter lesions, incomplete is-
chemic injury, hippocampal lesions, and sclerosis (Jellinger 2005). Several
subtypes of vascular dementia have been described, based on either the num-
ber and distribution of lesions or the size of vessels involved (large vs. small
vessels). An emerging consensus suggests that the “subcortical” pattern of
damage is sufficiently homogeneous in terms of clinical, radiographic, and
pathophysiological features to constitute a meaningful subtype, particularly
with respect to treatment trials. Generalized arteriosclerosis secondary to hy-
pertension, cerebral atherosclerosis, and diabetes usually are cited as the most
common causes of thrombotic infarction, and cardiac disease and carotid ath-
erosclerosis as the most common causes of embolic infarction. Increasing ev-
idence suggests that the vascular lesions of vascular dementia may affect
cholinergic pathways in vascular dementia, leading to a hypocholinergic state

similar to that observed in Alzheimer’s disease (Mesulam et al. 2003). Some
investigators (e.g., Roy and Rauk 2005) have hypothesized that both Alzhei-
mer’s disease and vascular dementia are the result of a common pathophysio-
logical process initiated by soluble β-amyloid, which is toxic to both neuronal
and vascular tissue. Others support the view that ischemia due to vascular pa-
thology triggers the cascade of events leading to the development of plaques
and tangles (Casserly and Topol 2004; Honig et al. 2003).
Prevention of Vascular Dementia

Treatment aimed at controlling hypertension has been shown to reduce the
risk of dementia and cognitive impairment (Forette et al. 2002; Tzourio et al.
2003), and prevention of cardiac arrhythmia and prescription of aspirin or
other antiplatelet-aggregating agents also may be of benefit (Nelson et al.
2003). Interestingly, statin therapy has not been of benefit in trials published
to date (Shepherd et al. 2002).
Treatment of Cognitive Impairment in Vascular Dementia

Three studies have reported the efficacy of cholinesterase inhibitors in vascu-
lar dementia: two studies with donepezil (Black et al. 2003; Wilkinson et al.
2003) and one study with galantamine (Erkinjuntti et al. 2002; in this study,
only subjects with “mixed” Alzheimer’s disease and vascular dementia bene-
fited from active treatment), and it is likely that rivastigmine and yet-to-be-
developed cholinesterase inhibitors are equally effective. These results are pre-
sumably based on the cholinergic deficit that has been identified in vascular
dementia, even though such a deficit is not required for cholinesterase inhib-
itors to be effective (Yesavage et al. 2002). Dosage and treatment outcomes in
vascular dementia are comparable in magnitude to those seen in Alzheimer’s
disease but appear to be a result of improvement in cognitive function com-
pared with placebo-treated subjects rather than a reduced rate of cognitive
decline, which is the typical pattern seen with cholinesterase inhibitors in
Alzheimer’s disease. Memantine also has been shown to be effective in vascu-
lar dementia, although benefits are minimal (Orgogozo et al. 2002; Wilcock
et al. 2002). Propentofylline, a glial cell modulator that has been shown to in-
terfere with neuroinflammatory processes linked to the pathological activa-
tion of microglial cells and reactive astrocytes (Kittner et al. 2000), has been
effective in early Phase II trials and warrants watching.
Treatment of Behavioral Complications, Mood Disorder,

and Psychosis in Vascular Dementia
Psychosocial and psychopharmacological therapy for behavioral complications
of vascular dementia follow the general principles outlined in Chapter 5 (“De-
mentia and Alzheimer’s Disease”) for Alzheimer’s disease, with the following ca-
veat. In 2004, the U.S. Food and Drug Administration (FDA) concluded on
the basis of its review of four randomized trials of risperidone in almost 1,800
elderly patients with dementia that risperidone was associated with an increased
risk of ischemic stroke; a subsequent analysis of a comparably large data set led
to the same conclusion about olanzapine. These findings led the FDA to issue
advisories to physicians and led several investigators to conduct confirmatory
studies. Moretti et al. (2005) studied 346 subjects with vascular dementia and
“behavioral problems” who were randomly assigned to 12 months of treatment
with conventional neuroleptics (about half received haloperidol, and half re-
ceived promazine) or olanzapine. They found that olanzapine was equal to con-
ventional neuroleptics for control of behavior problems but produced fewer
negative effects on gait, balance, and equilibrium and was not associated with
an increased incidence of stroke, myocardial infarction, or death. Herrmann et
al. (2004) studied a Canadian database of more than 1.4 million patients age
65 or older and found no increase in the crude rate of stroke when patients tak-
ing risperidone or olanzapine were compared with those who received a typical
neuroleptic. These studies and others like them are reassuring, but patients with
vascular dementia who are taking atypical agents should be monitored closely
for evidence of vascular complications.
Mixed Dementia
In a review, Langa et al. (2004) defined mixed dementia as “cognitive decline
sufficient to impair independent functioning in daily life resulting from the
coexistence of AD [Alzheimer’s disease] and cerebrovascular pathology, docu-
mented either by clinical criteria or by neuroimaging findings” (p. 2902). As
discussed earlier, the amyloid plaques and neurofibrillary tangles of Alzhei-
mer’s disease and the large infarctions, multiple lacunar infarctions, and is-
chemic periventricular leukoencephalopathy of vascular dementia are often

found together in the brains of individuals with dementia. Depending on the
source of pathological material, from 25% to 45% of Alzheimer’s disease
brains have significant vascular pathology (Langa et al. 2004), and plaques
and tangles are nearly always present in the brains of individuals with vascular
dementia, all of which leads to the conclusion that vascular dementia is actu-
ally mixed dementia in a large percentage of cases. Treatment follows guide-
lines for Alzheimer’s disease, with preventive efforts aimed at control of blood
pressure and other risk factors for vascular dementia.
Dementia Due to General Medical Conditions

Although many other conditions can cause impairment in cognition severe
enough to meet criteria for dementia (see Chapter 5, “Dementia and Alzhei-
mer’s Disease,” Table 5–6), DSM-IV-TR specifically recognizes HIV disease,
head trauma, Parkinson’s disease, Huntington’s disease, Creutzfeldt-Jakob
disease, and Pick’s disease (a form of frontotemporal dementia, described ear-
lier in the “Pathology” subsection of “Frontotemporal Dementia”) as capable
of causing dementia via direct damage to brain structures (by infection,
trauma, or degeneration). Differentiation of each of these conditions from
Alzheimer’s disease, frontotemporal dementia, dementia with Lewy bodies,
vascular dementia, and other dementing conditions depends on identifica-
tion of the characteristic physical and laboratory abnormalities associated
with each disease entity, supported by appropriate historical information.
These characteristics are summarized in Table 6–5.
Patients with the cognitive impairment associated with acquired immu-
nodeficiency syndrome (AIDS)—the AIDS dementia complex—typically
present with forgetfulness, inability to sustain attention to complex tasks, and
generalized mental slowing; these patients progress to a frank frontotemporal-
type dementia with apathy, loss of initiative, and significant psychomotor re-
tardation. Highly active antiretroviral therapy (HAART) has been reported to
improve memory, attention, and other cognitive functions in AIDS dementia
(Robertson et al. 2004), even though HAART agents poorly penetrate the
blood-brain barrier. Despite the benefits of HAART, most AIDS dementia
patients continue to have significant cognitive impairment even when viral
counts in brain tissue have declined to relatively low levels.
Table 6–5. Differentiating the common dementias

Cognitive and Imaging and
Type History Physical findings behavioral function laboratory findings
Alzheimer’s disease Gradual onset and Typically none until Language deficits early Cortical atrophy,
progression; ± family middle to late stages (word finding, anomia, ventricular
history fluent aphasia); clues enlargement on CT,
not helpful with MRI; temporal/parietal
retrieval; visuospatial hypometabolism on
deficits early PET; hypoperfusion on
SPECT
Vascular dementia Abrupt onset, stepwise Neurological signs and Patchy impairment; Stroke; lacunae in basal
decline; history of symptoms (e.g., gait depression, relative ganglia, white matter;
hypertension, abnormalities, falls, preservation of periventricular lesions
atherosclerosis incontinence) personality common very common, required
for diagnosis if focal
neurological signs
absent
HIV dementia HIV-positive blood test; Neurological signs and Forgetfulness, apathy, Elevated CSF protein;
gradual onset of symptoms may be slowness, poor mild lymphocytosis
cognitive changes present (e.g., ataxia, concentration common may be present;
tremor, “frontal release” neuroimaging
signs) nonspecific; HIV
usually present in CSF
Table 6–5. Differentiating the common dementias (continued)
Head trauma Head injury Depends on location of Memory impairment Depends on location,
injury; dysarthria, usually present; impulse extent of injury
hemiparesis common dyscontrol, irritability,
personality change may
be seen; nonprogressive
unless head trauma
repeated (e.g., in
dementia pugilistica)
Parkinson’s disease Dementia in later stages Extrapyramidal signs Cognitive slowing, poor Subcortical atrophy on
Other Dementias and Delirium

of neurological (e.g., tremor, gait recall, frontal signs CT (e.g., increased
syndrome disturbance, rigidity, (e.g., perseveration, intercaudate distance,
bradykinesia) decreased word-list ventricular
generation, impaired enlargement) common;
behavioral global cerebral
sequencing); clues metabolism also may be
helpful with memory diminished on PET
retrieval
Huntington’s disease Autosomal dominant “Fidgeting” progressing Personality change, loss CT or MRI may show
pattern of inheritance; to choreoathetosis of judgment, irritability striatal atrophy; PET
onset generally in 30s– early; memory may show striatal
40s; offspring of impairment later; hypometabolism
251
affected parent 50% psychosis common
likely to be affected
Table 6–5. Differentiating the common dementias (continued)

Pick’s disease Onset in 50s–60s Frontal release signs (e.g., Personality change, CT or MRI may show
snout, grasp reflex) emotional blunting, frontal and temporal
common deterioration of social atrophy; PET may show
skills, language deficits frontal
early; memory hypometabolism
impairment, dyspraxia
later
Creutzfeldt-Jakob Onset in 40s–60s; 5%– Myoclonus early, seizures Nonspecific symptoms CT and MRI may be
disease 15% have family later; ataxia, visual (e.g., fatigue, normal; EEG may show
history; rapid symptoms, gait diminished sleep and sharp, triphasic
progression (i.e., 1-year disturbance variably appetite early; global synchronous discharges
course) typical; can be present cognitive deficits late) at 0.5–2 Hz
transmitted by corneal
transplant or contact
with infected brain
tissue or CSF
Note. CSF= cerebrospinal fluid; CT= computed tomography; EEG =electroencephalogram; HIV=human immunodeficiency virus; MRI=magnetic
resonance imaging; PET= positron emission tomography; SPECT= single photon emission computed tomography.
Dementia associated with head trauma has been reported to respond to

cholinesterase inhibitors, with improvement in short-term memory and sus-
tained attention reported in one random-assignment, double-blind, placebo-
controlled crossover study (Zhang et al. 2004) and similar positive results
found in several open-label studies (Masanic et al. 2001; Morey et al. 2003).
The dementias of Parkinson’s disease and Huntington’s disease, like some
forms of vascular dementia, are sometimes described as “subcortical” because
they are characterized by a cluster of clinical features (relative preservation of
language function, visuoperceptual skills, and ability to do mathematical cal-
culations, with comparatively severe deficits in frontal executive functions, in-
cluding attention, verbal fluency, response inhibition, and ability to plan and
execute multistep actions) that are relatively less common in dementing ill-
nesses with primarily cortical pathology, such as Alzheimer’s disease. In the
early stages of these illnesses, patients may have subtle changes in executive
functions (especially problems in maintaining or shifting set) but do not yet
meet criteria for dementia. As the disease progresses, impaired learning and
retrieval efficiency appears, but problems with retention of learned material
may be absent or mild, except in those who have concomitant Alzheimer’s
disease, dementia with Lewy bodies, or other neurological disorders. Neuro-
psychological profiles of patients with Parkinson’s disease and dementia with
Lewy bodies are similar, but executive dysfunction is generally less severe in
Parkinson’s disease, and attentional fluctuations may be less pronounced.
Functionally significant cognitive deficits in Parkinson’s disease are quite vari-
able. Some patients with Parkinson’s disease develop noticeable cognitive def-
icits within a year or two of the onset of motor symptoms, others remain free
of all but minor executive deficits for 5–10 years, and many never show the
level of cognitive deficit that would be detected on mental status examina-
tions. A substantial proportion of patients with Parkinson’s disease (20%–
45%, according to Rickards [2005]) have significant depressive symptoms
that can compound mild cognitive impairments. Despite the differences in
pathophysiology between Alzheimer’s disease and Parkinson’s disease, treat-
ment trials with cholinesterase inhibitors have reported efficacy in Parkinson’s
dementia comparable to that seen in Alzheimer’s disease (Aarsland et al. 2002;
Emre et al. 2004; Giladi et al. 2003). However, no effective treatment for the
dementia of Huntington’s disease has yet been developed. Family members
caring for older adults with Parkinson’s disease, Huntington’s disease, or other
progressive neurological disorders may benefit from some of the same inter-
ventions as caregivers of patients with Alzheimer’s disease (see Chapter 5,
“Dementia and Alzheimer’s Disease”), including psychotherapy for marked
caregiver strain (e.g., Secker and Brown 2005).
Dementia Due to Other General Medical Conditions

Dementia also may be caused by other diseases with primarily central nervous
system pathology, such as multiple sclerosis, amyotrophic lateral sclerosis, and
various conditions (e.g., progressive subcortical gliosis, focal lobar atrophy)
with mainly frontal lobe–type behavioral manifestations. Extracerebral pa-
thology, both intracranial (brain tumor, subdural hematoma, hydrocephalus)
and extracranial (hypothyroidism, hypercalcemia, hypoglycemia) processes,
also can cause dementia via mechanical and biochemical effects on brain
function. Accurate diagnosis usually depends on recognition of the character-
istic clinical and laboratory features of the underlying illness. The battery sug-
gested in Table 5–4 in Chapter 5 (“Dementia and Alzheimer’s Disease”) is
designed to have relatively high sensitivity for this purpose.
Substance-Induced Persisting Dementia

Certain substances with central nervous system activity can produce both in-
toxication, during which cognitive impairment severe enough to otherwise
qualify as dementia may be present, and dementia per se, which persists for
months or years after the substance use is terminated (see Table 5–6). Alcohol
is perhaps the classic example of such a substance. Some patients with a diag-
nosis of alcoholic dementia have Korsakoff ’s syndrome, which is a pure am-
nesia due to damage to the mammillary bodies, dorsomedial nucleus of the
thalamus, and periaqueductal gray matter, with varying amounts of cortical
atrophy and ventricular enlargement. The syndrome is caused by thiamine
deficiency, usually in the context of severe and prolonged alcohol intake, and
has been reported to be responsive to cholinesterase inhibitors (Cochrane et
al. 2005) in case reports but not in a placebo-controlled, single-blind study of
malnutrition-related disease (Sahin et al. 2002). Other cases of “alcoholic de-
mentia” are probably cases of concomitant Alzheimer’s disease or vascular
dementia or reflect the effects of continued intoxication (Lishman 1987).
However, evidence indicates that substantial cognitive deficits beyond “pure”

amnesia are common in people who drink heavily and that even though these
deficits tend to remit after drinking is discontinued, some deficits may persist
for years and may in fact be permanent.
On neuropsychological testing, older adults with alcohol-related dementia
have relatively prominent subcortical dementia features, including reduced
mental control and executive function impairments, and some may show learn-
ing and memory problems similar to those of patients with Alzheimer’s disease
at comparable levels of dementia severity. For patients with Korsakoff ’s syn-
drome, memory deficits dominate the profile and may include tendencies to
confabulate or intrude irrelevant but related information into recall attempts.
Oslin and colleagues (1998) reviewed the literature and proposed the fol-
lowing diagnostic criteria for probable alcohol-related dementia:
1. A clinical diagnosis of dementia at least 60 days after the last exposure to
alcohol.
2. Significant alcohol use, as defined by a minimum average of 35 standard
drinks per week for men (28 for women) for more than 5 years. The pe-
riod of significant alcohol use must occur within 3 years of the initial on-
set of dementia.
Oslin and colleagues (1998) also proposed that supportive features include
alcohol-related organ system damage (e.g., hepatic, renal, pancreatic), ataxia or
peripheral sensory polyneuropathy, stabilization or improvement of the cog-
nitive impairment, improvement of neuroimaging evidence of sulcal or ven-
tricular dilatation after 60 days of abstinence, and neuroimaging evidence of
cerebellar atrophy, especially of the vermis. The observation that cognition and
functional status may improve, or at least stabilize, for older patients with alco-
hol-related dementia if they remain abstinent (Oslin and Cary 2003) under-
scores the importance of screening for alcohol problems in primary care and
psychiatric settings.
Reversible Dementia
Some dementias (mainly those due to a general medical condition), at least in
principle, can be arrested or reversed if the underlying condition is success-
fully treated before significant brain damage occurs. Clarfield (1988) re-
viewed several studies and found that 13% of dementias were potentially
reversible, but only 11% partially and 3% fully reversed. With more con-
servative criteria (excluding the dementia syndrome of depression), only 8%
reversed at all. Clarfield found that other than the dementia syndrome of de-
pression, substance-induced persisting dementia; metabolic dementia (in-
cluding thyroid and vitamin B12 [cobalamin] deficiency); and dementia
secondary to normal-pressure hydrocephalus, subdural hematoma, or brain
tumor were reversible. Osimani and colleagues (2005) confirmed the revers-
ibility of the dementia due to vitamin B12 deficiency and suggested that neu-
ropsychological evaluation could distinguish this syndrome from Alzheimer’s
disease. They found more frequent psychosis, minimal language disturbance,
and absence of ideomotor apraxia in dementia due to vitamin B12 deficiency
as compared with Alzheimer’s disease.
In 2003, Clarfield updated his meta-analysis and found that of more than
5,000 cases reviewed, potentially reversible causes were seen in 9%, and only
0.6% of the dementia cases actually reversed (0.29% partially, 0.31% fully).
Clarfield attributed the decline to improved selection criteria and more rigor-
ous methodology, resulting in the proportion of truly reversible dementias de-
clining toward its “true” very low value. Since Clarfield’s last review, cases of
reversible dementia also have been reported involving cerebral Whipple’s dis-
ease (Rossi et al. 2005); cryptococcal meningitis (Ala et al. 2004); bromide in-
toxication (Yu et al. 2004); systemic lupus erythematosus (Lee et al. 2004);
cerebral amyloid inflammatory vasculopathy (Harkness et al. 2004); and du-
ral arteriovenous fistula of the right transverse sinus and torcula, with occlu-
sion of the right sigmoid sinus (Bernstein et al. 2003). In general, the list of
organic etiologies that can cause dementia increases with the age of the pa-
tient, as declining functional brain reserve reduces the individual’s ability to
tolerate physiological derangement.
Delirium
Epidemiology
The prevalence of delirium depends on the population at risk and the diagnostic
criteria used. Bucht and associates (1999) reviewed the literature and found that
about 15% of elderly inpatients on acute medical-surgical services have delirium
at any time, and the rate is even higher among nursing home patients. The high-
est prevalence of delirium is in intensive care units, where rates of 70%–87%

have been reported (Ely et al. 2001; McNicoll et al. 2003). Well-established risk
factors include age and cognitive impairment, but studies also have identified
visual impairment, severe illness, and dehydration as risk factors, and use of phys-
ical restraints, malnutrition, addition of more than three medications while in
the hospital, use of bladder catheter, and iatrogenic events as precipitating factors
that sequentially increase the risk of delirium (Inouye 2000).
Diagnostic Criteria
DSM-IV-TR diagnostic criteria for delirium due to a general medical condi-
tion are summarized in Table 6–6.
History and Clinical Presentation

Four specific subtypes of delirium are recognized in DSM-IV-TR: 1) delirium
due to a general medical condition, 2) delirium due to substance intoxication,
3) delirium due to substance withdrawal, and 4) delirium due to multiple eti-
ologies. Obviously, the patient’s recent history is critical in distinguishing
among these possibilities. Delirium due to a general medical condition usually
develops over hours to days, and the medical history is typically that of the pri-
mary illness, with a superimposed history of the development of disturbance in
consciousness and cognition. For obvious reasons, the patient with delirium
usually cannot give a reliable history of the current illness, which is obtained
from friends, family, hospital personnel, or the medical record. Because delir-
ium occurs as an emergent complication of several life-threatening illnesses, it
is important to complete the evaluation rapidly. A recent history of drug or al-
cohol ingestion will be present in cases of substance intoxication delirium, and
a history of abrupt discontinuation of prolonged, high-dose ingestion will be
present in cases of substance withdrawal delirium. Delirium frequently coexists
with dementia and sometimes can be mistaken for dementia. Table 6–7 reviews
the key differences between the two syndromes.

As indicated in Table 6–6, DSM-IV-TR recognizes the most prominent fea-
tures of delirium as “reduced clarity of awareness of the environment” with
“reduced ability to focus, sustain, or shift attention” (American Psychiatric
Table 6–6. Summary of DSM-IV-TR diagnostic criteria for delirium

due to a general medical condition
A. Disturbance of consciousness (i.e., reduced clarity of awareness of the
environment) with reduced ability to focus, sustain, or shift attention.
B. A change in cognition or the development of a perceptual disturbance that is
not better accounted for by a preexisting, established, or evolving dementia.
C. The disturbance develops over a short period of time (usually hours to days)
and tends to fluctuate during the course of the day.
D. There is evidence from the history, physical examination, or laboratory findings
that the disturbance is caused by the direct physiological consequences of a
general medical condition.
Association 2000, p. 143). Several authorities on delirium have further subdi-

vided the disorder into the following categories: 1) “somnolent or hypoactive”
and 2) “activated or hyperactive.” In both types, the patient has either cognitive
impairment, such as a deficit in orientation, memory, or language function, or
“perceptual disturbance that is not better accounted for by…dementia” (Amer-
ican Psychiatric Association 2000, p. 143). Ross and colleagues (1991) found
hallucinations and delusions to be far more common in patients with “acti-
vated” than with “somnolent” delirium, and our clinical experience is the same.
Unlike uncomplicated dementia, the cognitive deficits in delirium are rarely
disguised by the patient’s attempts to cover or minimize deficits but may none-
theless be overlooked by clinicians, particularly when the delirium is mild or ac-
companied by significant somnolence. More commonly, the patient with
delirium cannot participate in a thorough mental status examination, and the
syndrome is identified indirectly.
Trzepacz and colleagues (Trzepacz and Dew 1995; Trzepacz et al. 1988)
developed a 10-item Delirium Rating Scale, which can be used to quantify
delirium severity and treatment response and may help to differentiate delir-
ium from psychotic episodes or dementia; in 2000, this scale was updated to
a 16-item version that has increased flexibility and breadth of symptom cov-
erage, with comparable reliability and validity (Trzepacz et al. 2001). Another
instrument, the Confusion Assessment Method (CAM; Inouye et al. 1990)
Table 6–7. Differentiating delirium from dementia

Feature Delirium Dementia
Onset Abrupt/subacute Insidious

Course Fluctuating Slow progression
Duration Hours to weeks Months to years
Alertness Abnormally high or low Typically normal
Sleep-wake Disrupted Typically normal
Attention Impaired Relatively normal
Orientation Impaired Intact in early dementia
Working memory Impaired Intact in early dementia
Episodic memory Impaired Impaired
Thought Disorganized, delusions Impoverished
Speech Slow/rapid, incoherent Word finding difficulty
Perception Illusions and hallucinations Usually intact in early
common dementia
Behavior Withdrawn or agitated Varies, often intact early
Source. Adapted from Butler C, Zeman AZ: “Neurological Syndromes Which Can Be Mis-
taken for Psychiatric Conditions.” Journal of Neurology, Neurosurgery, and Psychiatry 76:i31–i38,
2005. Reproduced with permission from the BMJ Publishing Group.
(Table 6–8), is based on diagnostic criteria from DSM-III-R (American Psy-

chiatric Association 1987) and has very high (i.e., >90%) positive predictive
accuracy for the recognition of delirium. The relatively shorter and easier to
administer CAM and the Delirium Rating Scale (original 10-item version)
showed good to very good agreement in the classification of delirium among
older acutely ill hospital inpatients in a study of 94 subjects (Adamis et al.
2005); agreement was strongest with the more sensitive Delirium Rating
Scale cutoff point of 10. An even shorter version of the CAM, which can be
administered to intubated patients and does not require verbal responses, has
been developed and appears to have specificity and sensitivity comparable to
the “standard” version (McNicoll et al. 2005).
Proper evaluation of delirium requires comprehensive medical evaluation, in-
cluding a complete physical and neurological examination and laboratory
Table 6–8. Confusion Assessment Method (CAM) algorithm

1. Acute onset and fluctuating course
Indicated by positive responses to the following questions:
Is there evidence of an acute change in mental status from the patient’s
baseline?
AND
Did this behavior fluctuate during the past day—that is, tend to come and
go or increase and decrease in severity?
2. Inattention
Indicated by a positive response to the following question:
Does the patient have difficulty focusing attention—for example, being
easily distractible or having difficulty keeping track of what is being said?
3. Disorganized thinking
Indicated by a positive response to the following question:
Is the patient’s speech disorganized or incoherent, with rambling or
irrelevant conversation, unclear or illogical flow of ideas, or unpredictable
switching from subject to subject?
4. Altered level of consciousness
Indicated by any response other than alert (normal) to the following question:
Overall, how would you rate this patient’s level of consciousness?
Alert (normal)
Vigilant (hyperalert)
Lethargic (drowsy, easily aroused)
Stupor (difficult to arouse)
Coma (unarousable)
Note. The diagnosis of delirium requires a present or abnormal rating for criteria 1, 2, and
3 or 4.
Source. Adapted from Inouye et al. 1990.
tests as needed. Delirium is usually discovered by psychiatrists in a consulta-

tion role, after nonpsychiatric personnel have done the physical examination.
Similarly, laboratory evaluation may have been substantially completed be-
fore consultation was requested; the battery of tests listed in Table 6–9 is
rather broad and usually can be narrowed in the actual clinical situation, de-
pending on the differential diagnosis of the primary illness.
Table 6–9. Laboratory evaluation of delirium

Screening studies
Blood studies
Complete blood count (hematocrit, white blood cell count and
differential, mean corpuscular volume, sedimentation rate)
Electrolytes, serum urea nitrogen, glucose, calcium, albumin, ammonia
(NH4), liver function tests
Drug levels (toxic screen, medication levels)
Arterial blood gases
Urinalysis, including acetone and glucose
Chest X ray
Electrocardiogram
Additional studies based on clinical judgment, in light of above studies
Blood studies
Heavy metals
Thiamine and folate levels
Thyroid function tests
Lupus erythematosus preparation
Antinuclear antibodies
Urinary porphobilinogen
Lumbar puncture
Computed tomography or magnetic resonance imaging of the head
Electroencephalogram
Source. Adapted from Wise MG, Trzepacz PT: “Delirium (Confusional States),” in The Amer-
ican Psychiatric Press Textbook of Consultation-Liaison Psychiatry. Edited by Rundell JR, Wise MG.
Washington, DC, American Psychiatric Press, 1996, p. 267. Copyright © 1996, American Psy-
chiatric Press. Used with permission.
In addition to identifying the primary illness underlying delirium, the clini-
cian must rule out other psychiatric illnesses that have signs and symptoms
similar to those of true delirium. As mentioned earlier, dementia can mimic
delirium, particularly when agitation, psychosis, or anxiety is superimposed. In
these circumstances, the clinical picture of a disorganized, aroused, confused
patient with poor attention and concentration is virtually indistinguishable
from that of delirium, and even when the clinician knows that the patient has
dementia, he or she is often obliged to conduct a rapid “mini-evaluation” in
which potential causes of delirium, particularly medications with central
anticholinergic effects and infection, are ruled out. This “pseudodelirium” is
usually self-limited and of very brief duration (minutes to hours), is not ac-
companied by alterations in the level of consciousness, and may be rapidly re-
sponsive to simple reassurance or other behavioral interventions. Functional
disorders, including mania, hypomania, depression, hysteria, and schizophre-
nia, particularly in the severe manifestations known as manic delirium and
catatonic excitement, also can present with a clinical state that can be difficult
to distinguish from delirium caused by a general medical condition or a psy-
choactive substance.
Pathogenesis
The precise mechanism underlying the clinical picture of delirium is not

known, although a final common pathway involving a disturbed balance be-
tween central cholinergic and dopaminergic neurons that mediate attention
and arousal has been postulated (Trzepacz 2000). Indirect evidence for this
hypothesis includes the fact that cholinergic neurons appear to be the most
sensitive to cerebral ischemia and hypoxia, which are fairly potent clinical
causes of delirium, and the observation that centrally acting anticholinergic
drugs can produce a delirium in otherwise intact individuals that can be re-
versed by cholinergic-enhancing agents (Kobayashi et al. 2004; Noyan et al.
2003). Because aging is accompanied by reduced central cholinergic tone and
many elderly patients have compromised cardiovascular and pulmonary func-
tions, rendering them susceptible to ischemia and hypoxia, it is not surprising
that age is a major risk factor for the development of delirium. Cognitive im-
pairment is also a major risk factor for the development of delirium, probably
because of the reduced central cholinergic tone common to Alzheimer’s dis-
ease, vascular dementia, and other common dementing illnesses (Korevaar et
al. 2005). However, other mechanisms also have been proposed; in the delir-
ium of hepatic encephalopathy, the role of an endogenous benzodiazepine-
like substance is evident, the pathogenic activity of which may be partially
blocked by benzodiazepine antagonists such as flumazenil.
Treatment
The first priority is to identify emergent, life-threatening causes of delirium and

correct them if possible. The most hazardous of these causes are acute cerebral
ischemia or hypoxia; infection of the central nervous system (meningitis, en-
cephalitis, abscess); intracranial hemorrhage or infarction; acute intoxication
with central nervous system depressants, stimulants, or anticholinergic agents,
or combinations thereof; acute withdrawal of alcohol or other central nervous
system depressants; hypoglycemia and hyperglycemia with or without ketoaci-
dosis; acid–base or electrolyte imbalance; acute hyperthyroidism (i.e., “thyroid
storm”); and hypertensive encephalopathy. However, treatment of delirium is
important even if the underlying causes are not immediately life threatening be-
cause evidence shows that the presence of delirium per se (i.e., even when cor-
rected for severity of underlying illness) at the time of admission adversely
affects rates of posthospitalization mortality, functional decline, and nursing
home placement (Inouye et al. 1998).
Specific Psychopharmacotherapy
Two subtypes of delirium call for specific pharmacological therapy. First, with-
drawal of alcohol, benzodiazepines, or barbiturates can produce a charac-
teristic delirium (delirium tremens, in its most severe form) that is rapidly
responsive to replacement therapy with any of the three agents. Practically,
benzodiazepines are the treatment of choice and are usually administered
parenterally until symptoms are under control, at which time oral administra-
tion can be initiated. Lorazepam, a benzodiazepine with the most reliable ab-
sorption after intramuscular injection, has the additional advantages in elderly
patients of having no active metabolites and undergoing one-step hepatic me-
tabolism (i.e., conjugation) that is relatively insensitive to the presence of liver
disease. Lorazepam may be administered in doses of 0.5 mg every hour until
symptoms are under control; in more acute situations, intravenous administra-
tion provides more rapid onset of action. The second type of delirium respon-
sive to specific psychopharmacotherapy is that caused by centrally acting
anticholinergic agents. When withdrawal of the offending agent and support-
ive therapy are ineffective, further amelioration of symptoms can be attained
with oral administration of cholinesterase inhibitors such as donepezil or
parenteral administration of physostigmine, a more rapidly acting cholines-
terase inhibitor. The typical dose of donepezil is 5–10 mg/day administered

orally; the dosage of physostigmine is 2 mg administered intramuscularly or by
slow intravenous push. Because physostigmine has a duration of action of only
about 60 minutes, whereas most anticholinergic agents are somewhat longer
acting, a switch to oral agents may be warranted after acute reversal of symp-
toms with physostigmine; alternatively, additional doses of physostigmine may
be administered until the situation has stabilized.
Nonspecific Psychopharmacotherapy
In most other situations in which rapid control of symptoms of delirium is
desired, a growing body of case reports suggests that empirical administration
of oral cholinesterase inhibitors (donepezil, rivastigmine, galantamine)
should be followed by administration of a high-potency neuroleptic agent
such as haloperidol, risperidone, or olanzapine as necessary. Although neuro-
leptics may not correct the pathophysiology underlying delirium, they can
control agitation and thereby reduce the danger of self-inflicted injury, ex-
haustion, or disconnection from vital extracorporeal supports and render the
patient more cooperative with appropriate diagnostic and therapeutic inter-
ventions. Dosages and routes of administration vary depending on the sever-
ity of the clinical situation. Intravenous or intramuscular administration of
0.5–2.0 mg of haloperidol or intramuscular administration of 2.5–5.0 mg of
olanzapine is appropriate when rapid control of symptoms is required. In a
less acute situation, 0.5–1.0 mg of haloperidol or risperidone administered
orally is effective (Han and Kim 2004). When symptoms are refractory, aug-
mentation with 0.5 mg of lorazepam is usually very effective.
Prognosis
One-quarter or more of elderly patients who develop delirium during acute

hospitalization continue to have symptoms such as inattention, reduced
awareness of the environment, and temporal disorientation for up to 6
months after discharge (Levkoff et al. 1994). The long-term prognosis of de-
lirium is primarily determined by the underlying illnesses, and most of the lit-
erature in this area is disease specific; however, most studies agree that
delirium per se increases the risk of functional decline and death.
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7
Anxiety Disorders and
Late-Onset Psychosis
Anxiety Disorders
Epidemiology
The Epidemiologic Catchment Area survey found anxiety disorders to be the
most common mental illnesses, with a 1-month prevalence of 7.3% in adults
of all ages (Regier et al. 1988). However, a lower prevalence of 5.5% was
found in adults older than 65; within this group, phobic disorders (4.8%),
obsessive-compulsive disorder (OCD; 0.8%), and panic disorder (0.1%) were
the most prevalent specific disorders. Generalized anxiety disorder (GAD)
was not surveyed in the first wave of this study, but the second wave found a
6-month prevalence of GAD of 1.9% in adults age 65 or older, in whom only
3% of the cases began after age 65 (Blazer et al. 1991). Subsequent studies
converge on higher prevalence rates than those reported by Regier and col-
leagues. Krasucki et al. (1998) and Ritchie et al. (2004) reported an overall
prevalence of anxiety disorders of between 12% and 20%, depending mainly
on how agoraphobia was defined.
Accurate diagnosis of anxiety disorders in elderly patients can be particu-
larly difficult because of the great overlap between symptoms of anxiety dis-
orders and anxiety symptoms seen in other Axis I conditions, particularly
depression, dementia, and late-onset psychosis. A Dutch study of 3,056 indi-
viduals ages 55–85 found that 47.5% of those with major depressive disorder
also met criteria for anxiety disorders, whereas 26.1% of those with anxiety
273
disorders also met criteria for major depressive disorder (Beekman et al.
2000). In some cases, it can also be difficult to distinguish anxiety symptoms
from symptoms of physical illnesses such as cardiac and pulmonary condi-
tions (e.g., palpitations, shortness of breath, chest pain) that are common in
elderly persons.
Whether anxiety occurs in reaction to a transient situation, in reaction to a per-
manent or semipermanent life change, or as part of an anxiety disorder or
other Axis I disorder, patients with anxiety present with a subjective state of
dysphoric apprehension or expectation, accompanied by various combinations
of the signs and symptoms listed in Table 7–1 (which includes features listed
in DSM-IV-TR [American Psychiatric Association 2000] criteria for panic at-
tack and for GAD). Because the current generations of elderly individuals are
especially disinclined to complain of mental distress, anxious elderly patients
often focus on these physical features rather than on the subjective state of ap-
prehension or dysphoria per se. Unfortunately, their complaints often mislead
the general practitioner or internist into an extensive medical evaluation before
the correct diagnosis is established.
Recognition and treatment of anxiety disorders is important because of
the effect these disorders have on quality of life and because they are associ-
ated with a significantly increased risk of suicide attempts and completed sui-
cide, even in the absence of other mental disorders (Khan et al. 2002).
Geriatric depression is often slower to remit when the clinical picture is com-
plicated by comorbid general anxiety symptoms, panic disorder, or posttrau-
matic stress disorder (Hegel et al. 2005; Steffens and McQuoid 2005).
Anxiety also may be a predictor of cognitive decline, especially when accom-
panied by complaints of loss of memory (Sinoff and Werner 2003).
Anxiety Rating Scales

Both observer-rated measures, such as the Hamilton Anxiety Rating Scale
(Hamilton 1959), and self-rated instruments, such the Spielberger State-Trait
Anxiety Inventory (Spielberger et al. 1970) and the Worry Scale (Wisocki et
al. 1986), assess severity and type of anxiety symptoms. The Hamilton scale,
which consists of 14 items to assess 89 symptoms, has been the most widely
used test in psychiatric research, and a few studies support its utility with el-
Anxiety Disorders and Late-Onset Psychosis 275
Table 7–1. Autonomic and psychomotor features of anxiety

Generalized anxiety disorder
Restlessness or feeling keyed up or on edge
Being easily fatigued
Difficulty concentrating or mind going blank
Irritability
Muscle tension
Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
Panic attacka
Palpitations, pounding heart, or accelerated heart rate
Sweating
Trembling or shaking
Sensations of shortness of breath or smothering
Feeling of choking
Chest pain or discomfort
Nausea or abdominal distress
Feeling dizzy, unsteady, light-headed, or faint
Derealization (feelings of unreality) or depersonalization (being detached from
oneself )
Fear of losing control or going crazy
Fear of dying
Paresthesias (numbness or tingling sensations)
Chills or hot flushes
aPanicattack is diagnosed if four or more of these symptoms develop abruptly and reach a peak
within 10 minutes.
derly patients (J.G. Beck et al. 1996). The Spielberger scale includes items
that assess both current (“state”) and habitual (“trait”) anxiety symptoms. It
has proved useful as an outcome measure in studies of psychological interven-
tions to reduce anxiety in both young adult and elderly subjects but has been
less widely applied in pharmacological research. The Worry Scale was specif-
ically developed for use with older adults; the 35 items reflect severity of
worry about financial, health, and social concerns. It is useful in assessing se-
verity of anxiety symptoms in both the general population of older adults and
those with GAD (J.G. Beck et al. 1996). Other self-rated anxiety scales that
have been used in clinical geriatric research include the Beck Anxiety Inven-
tory (A.T. Beck et al. 1988) and the Penn State Worry Questionnaire (Hopko
et al. 2003). Additional information on anxiety assessment procedures appro-
priate for older adults can be found in Carmin et al. (1999).
Laboratory evaluation of the elderly patient with anxiety is aimed at ruling
out physical, chemical, and iatrogenic factors that can cause or exacerbate
anxiety and related symptoms. When laboratory evaluation results in a diag-
nosis of a physical illness (e.g., hyperthyroidism) that can explain the anxiety
symptoms, anxiety disorder due to a general medical condition is the correct
diagnosis. If a medication or other chemical (e.g., aminophylline) is identified
as the cause, substance-induced anxiety disorder is diagnosed. A functional
anxiety disorder may be exacerbated, but not caused, by medical illness or
substance use; thus, clinical judgment regarding the relative contribution of
the medical illness or medication is required to determine the correct diagno-
sis. Table 7–2 lists common medical conditions, chemicals, and medications
that can cause anxiety.
Situational Anxiety
Common situations in which elderly patients experience anxiety are very sim-
ilar to those that affect adults of all ages. These situations include those con-
ventionally acknowledged to provoke anxiety, such as a visit to the dentist or
doctor or an airplane flight, as well as those that may seem more idiosyncratic,
such as being asked simple mental status examination questions, conducting
a transaction with an accountant or a bank teller, or being asked to drive an
unfamiliar car. Unlike specific phobia, situational anxiety may not signifi-
cantly interfere with the person’s normal routine and, in that sense, may be
considered nonpathological; in fact, it does not appear in DSM-IV-TR. It is
mentioned here as a “subsyndromal” complaint for which medications may
be requested and may be effective.
Adjustment Anxiety
In elderly persons, adjustment reactions with anxiety may occur during or af-
ter periods of obvious personal crisis and in relation to crises that may not
seem particularly stressful to evaluating professionals. For example, a simple
Table 7–2. General medical conditions and medications that can

produce symptoms of anxiety
General medical conditions
Hyperadrenocorticism
Hyperthyroidisma
Hypoadrenocorticism
Hypoglycemia (any cause)
Insulinoma with hypoglycemia
Pheochromocytoma
Medications
Anticholinergics—atropine, scopolamine
Antidepressants—fluoxetine,a tranylcypromine
Caffeinea
Psychostimulants—amphetamine, cocaine, methylphenidate
Sympathomimetics
Decongestants—phenylephrine, phenylpropanolamine, pseudoephedrine,
ephedrine
Bronchodilators—albuterol, epinephrine, isoproterenol, metaproterenol
Xanthine derivatives—theophylline,a aminophyllinea
Medication withdrawal—alcohol,a benzodiazepines (especially short-acting
agents),a other central nervous system depressantsa
aRelatively
common offenders in the authors’ experience.
move from one apartment to another, even within the same neighborhood,
or from one room in a retirement hotel or nursing home to another may pre-
cipitate significant anxiety. Similarly, development of a new physical illness,
even one that is not life threatening or particularly disabling, may precipitate
significant anxiety. Other events that commonly elicit adjustment anxiety in-
clude divorce or illness in the family, business or financial reversals, marital
strife, or even a long-awaited retirement.
Generalized Anxiety Disorder
GAD is the second most common anxiety disorder in the elderly (after phobic
disorders) and the one most commonly comorbid with depressive illness.
DSM-IV-TR diagnostic criteria for GAD are summarized in Table 7–3. As it
is for phobic disorders, the female-to-male ratio for GAD is about 2:1. Lenze
and colleagues (2000) found that 27% of 182 elderly patients with depressive
disorder also met criteria for GAD and that symptoms of GAD were associ-
ated with a higher level of suicidality. In a follow-up study, Lenze and col-
leagues (2005a) found that the average age at onset of GAD in 103 elderly
subjects was 48.8. Although 47% had onset “later in life,” few differences
were found between early- and late-onset cases. GAD tended to be a single,
chronic episode, whereas subjects with comorbid major depressive disorder
tended to have recurrent depressive episodes. The most common lifetime pat-
tern of comorbidity was GAD preceding major depressive disorder, and Lenze
et al. (2005a) found that GAD tends to persist, with spontaneous remission
(without treatment) unlikely even if comorbid major depressive disorder re-
mits. The authors interpreted this finding as enhancing the rationale for long-
term treatment of GAD. In another recent study (Le Roux et al. 2005), older
adults with onset of GAD before age 50 years were found to have a higher rate
of psychiatric comorbidity, greater psychotropic use, and more severe worry
compared with GAD patients with later ages at onset, whereas late-onset pa-
tients reported more functional limitations resulting from physical problems.
An earlier report based on the same sample compared frequency of DSM-IV
(American Psychiatric Association 1994) anxiety symptoms for older adults
with GAD, subsyndromal anxiety, or no mental disorder (Wetherell et al.
2003b). Frequency and uncontrollability of worry, degree of distress or im-
pairment associated with worry, muscle tension, and sleep disturbance were
the symptoms most likely to distinguish GAD from the other conditions.
Worrying about family members was common in all groups (endorsed by
69% of control subjects with no mental disorder, 91% with subsyndromal
anxiety, and 90% with GAD), whereas worries about oneself were elevated in
the GAD group, with health concerns, worries about minor matters, and fi-
nancial concerns predominating. About one-third of older individuals in each
group reported worries about community or world affairs.
Phobias
Phobias include the DSM-IV-TR categories of specific phobia, social phobia,
and agoraphobia without history of panic disorder. Taken together, phobias
constitute the most common anxiety disorder among elderly individuals, with
a reported prevalence between 0.7% and 12%, with results of most studies fall-
ing in the 3%–12% range, depending on inclusion criteria and the period of

generalized anxiety disorder
A. Excessive anxiety and worry (apprehensive expectation) occurring more days
than not for at least 6 months, about a number of events or activities (such as
work or school performance).
B. The person finds it difficult to control the worry.
C. The anxiety and worry are associated with three (or more) of the six symptoms
listed under generalized anxiety disorder in Table 7–1, with at least some
symptoms present for more days than not for the past 6 months.
D. The focus of the anxiety and worry is not confined to features of an Axis I
disorder (e.g., the anxiety and worry are not about having a panic attack, being
embarrassed in public, or being contaminated), and the anxiety and worry do
not occur exclusively during posttraumatic stress disorder.
E. The anxiety, worry, or physical symptoms cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
F. The disturbance is not due to the direct physiological effects of a substance or
a general medical condition and does not occur exclusively during a mood
disorder or a psychotic disorder.
prevalence (i.e., 1–6 months) studied. Most of the variability in prevalence

seems to stem from different ways to define agoraphobia, because rates of spe-
cific phobia and social phobia are more consistently reported at about 2%–6%
and 0.6%–1.2%, respectively, with the prevalence in elderly females about
twice that in elderly males (Krasucki et al. 1998; Ritchie et al. 2004). DSM-
IV-TR criteria for specific phobia are summarized in Table 7–4.
New onset of phobic symptoms in elderly patients requires thorough clin-
ical investigation because in some cases, the fear actually may not be so un-
reasonable. For example, older patients may become reluctant to join friends
for a game of bridge because they fear being unable to follow the action or
having an episode of incontinence, and subsequent investigation by the clini-
cian may detect for the first time that such mishaps have actually occurred.
Obsessive-Compulsive Disorder
Late onset of OCD appears to be quite rare, with most epidemiological stud-
ies reporting rates in the 1% range, with a predominance of females that is
Table 7–4. Summary of DSM-IV-TR diagnostic criteria for specific

phobia
A. Marked and persistent fear that is excessive or unreasonable, cued by the presence
or anticipation of a specific object or situation.
B. Exposure to the phobic stimulus almost invariably provokes an immediate
anxiety response, which may take the form of a situationally bound or
situationally predisposed panic attack.
C. The person recognizes that the fear is excessive or unreasonable.
D. The phobic situation is avoided or else is endured with intense anxiety or distress.
E. The avoidance, anxious anticipation, or distress in the feared situation interferes
significantly with the person’s normal routine, occupational functioning, or
social activities or relationships, or there is marked distress about having the
phobia.
F. In individuals under age 18 years, the duration is at least 6 months.
G. The anxiety, panic attacks, or phobic avoidance associated with the specific
object or situation is not better accounted for by another mental disorder, such
as obsessive-compulsive disorder or posttraumatic stress disorder.
significantly less pronounced than in other anxiety disorders. The pattern of

symptoms is similar to that seen in younger patients, with a few minor differ-
ences: elderly patients have fewer concerns about symmetry, need to know,
and counting rituals, whereas hand washing and fear of having sinned are
more common in elderly patients (Kohn et al. 1997). Several reports sug-
gested that late-onset OCD is frequently associated with organic brain dis-
ease, including stroke, transient ischemic attack, and organophosphate
poisoning (Carmin et al. 2002; Philpot and Banerjee 1998; Weiss and Jenike
2000). Some older patients with chronic OCD seek medical attention only
when supervening age-related changes or superimposed mood disorder or de-
mentia forces them into treatment. In this situation, the likelihood that com-
pulsive rituals have become ego-syntonic and are no longer seen as irrational
is increased, and the clinician may need to explore the early history of the dis-
order to obtain a less misleading picture. Transient outbreaks of obsessive
thoughts and compulsive rituals are not uncommon among elderly patients
with major depression with or without psychosis. DSM-IV-TR allows a diag-
nosis of OCD in this circumstance if the content of the obsessions or com-

pulsions is not mood congruent (Table 7–5).
Panic Disorder
Elderly patients with panic disorder (with or without agoraphobia) report less
severe and fewer panic symptoms, less anxiety and arousal, lower levels of de-
pression, and higher levels of functioning than do middle-aged patients with
panic disorder, and older patients with late-onset panic disorder report less
distress related to panic symptoms than do elderly patients with early-onset
panic disorder (Sheikh et al. 2004b). Many older patients with panic disorder,
particularly of late onset, present first to their family physician or internist,
who is likely to initiate an evaluation for possible myocardial infarction, tran-
sient ischemic attack, or other episodic, life-threatening physical illness. It
may require several panic attacks accompanied by negative laboratory test re-
sults before the primary care physician identifies the correct diagnosis and
seeks psychiatric consultation. Patients and family members are often reluc-
tant to accept that something as terrifying as a panic attack can be “mental,”
and patients may avoid evaluation by the mental health professional because
they fear that they are “losing their minds” or “going crazy.” As defined by
DSM-IV-TR (Table 7–6), the diagnosis of panic disorder requires the occur-
rence of panic attacks and significant anticipatory anxiety, and successful
pharmacological amelioration of panic attacks is only part of the therapeutic
challenge. Anticipatory anxiety itself, without panic attacks, can be quite dis-
abling, and evidence is accumulating that combining pharmacotherapy with
cognitive-behavioral, behavioral, or supportive psychotherapy results in more
complete relief of symptoms.
Posttraumatic Stress Disorder
The literature on posttraumatic stress disorder (PTSD) in elderly individuals
presents conflicting views. Some researchers believe that elderly people are
more vulnerable to traumatic events than are younger people (Lyons and Mc-
Clendon 1990). The “differential vulnerability hypothesis” suggests that
adaptive capacities, coping resources, and external resources diminish with
age, whereas exposure to traumatic events or illnesses increases. On the other
hand, the “inoculation hypothesis” proposed by Eysenck (1983) maintains
that exposure to stress or a previous crisis could increase resistance to subse-

obsessive-compulsive disorder
A. Either obsessions or compulsions:
Obsessions as defined by (1), (2), (3), and (4):
(1) recurrent and persistent thoughts, impulses, or images that are experienced,
at some time during the disturbance, as intrusive and inappropriate and
that cause marked anxiety or distress
(2) the thoughts, impulses, or images are not simply excessive worries about
real-life problems
(3) the person attempts to ignore or suppress such thoughts, impulses, or
images or to neutralize them with some other thought or action
(4) the person recognizes that the obsessional thoughts, impulses, or images
are a product of his or her own mind (not imposed from without as in
thought insertion)
Compulsions as defined by (1) and (2):
(1) repetitive behaviors or mental acts (e.g., praying, counting, repeating words
silently) that the person feels driven to perform in response to an obsession,
or according to rules that must be applied rigidly
(2) the behaviors or mental acts are aimed at preventing or reducing distress
or preventing some dreaded event or situation; however, these behaviors
or mental acts either are not connected in a realistic way with what they
are designed to neutralize or prevent or are clearly excessive
B. At some point during the course of the disorder, the person has recognized that
the obsessions or compulsions are excessive or unreasonable.
C. The obsessions or compulsions cause marked distress, are time-consuming (take
more than 1 hour a day), or significantly interfere with the person’s normal
routine, occupational functioning, or usual social activities or relationships.
D. If another Axis I disorder is present, the content of the obsessions or compulsions
is not restricted to it.
E. The disturbance is not due to the direct physiological effects of a substance or
quent stress and enable elderly people to develop the coping strategies to
adapt successfully to traumatic events. However, data from a more recent
study of 148 survivors of two traumatic events, an airplane crash and a train
crash (Chung et al. 2004), suggest that neither the vulnerability hypothesis
Table 7–6. Summary of DSM-IV-TR diagnostic criteria for panic

disorder with or without agoraphobia
A. Both (1) and (2):
(1) recurrent unexpected panic attacks
(2) at least one of the attacks has been followed by 1 month (or more) of one
(or more) of the following:
(a) persistent concern about having additional attacks
(b) worry about the implications of the attack or its consequences
(c) a significant change in behavior related to the attacks
B. Presence or absence of agoraphobia.
C. The panic attacks are not due to the direct physiological effects of a substance
or a general medical condition.
D. The panic attacks are not better accounted for by another mental disorder, such
as social phobia or specific phobia.
nor the inoculation hypothesis applied to this cohort of community residents.

Instead, the investigators found that levels of intrusive thoughts, avoidance
behavior, coping strategies used, and subsequent general health problems
were similar across age groups. Diagnostic criteria for PTSD are summarized
in Table 7–7.
Mood Disorder With Anxiety
Anxiety symptoms are often a prominent part of major depression, dys-
thymia, bipolar disorder, and cyclothymia, and as described earlier, co-occur-
rence of full mood and anxiety syndromes is common. One large-scale study
of elderly primary care patients with major depression or dysthymia found
that patients with comorbid panic disorder or PTSD had substantially greater
psychiatric and medical illness than did those without comorbid anxiety. Pa-
tients with comorbid panic disorder or PTSD were more likely to report sui-
cidal thoughts at baseline and had a higher prevalence of chronic medical
illnesses, greater functional impairment, and a lower quality of life (Hegel et
al. 2005). Differentiation of dysphoric states into depressed mood or anxiety
may be particularly difficult with the current generations of elderly individu-

posttraumatic stress disorder
A. The person has been exposed to a traumatic event in which both of the following
were present:
(1) The person experienced, witnessed, or was confronted with an event or
events that involved actual or threatened death or serious injury, or a threat
to the physical integrity of self or others.
(2) The person’s response involved intense fear, helplessness,
or horror.
B. The traumatic event is persistently reexperienced in one (or more) of the
following ways:
(1) recurrent and intrusive distressing recollections of the event, including
images, thoughts, or perceptions
(2) recurrent distressing dreams of the event
(3) acting or feeling as if the traumatic event were recurring (includes a sense
of reliving the experience, illusions, hallucinations, and dissociative
flashback episodes, including those that occur on awakening or when
intoxicated)
(4) intense psychological distress at exposure to internal or external cues that
symbolize or resemble an aspect of the traumatic event
(5) physiological reactivity on exposure to internal or external cues that
symbolize or resemble an aspect of the traumatic event
C. Persistent avoidance of stimuli associated with the trauma and numbing of
general responsiveness (not present before the trauma), as indicated by three (or
more) of the following:
(1) efforts to avoid thoughts, feelings, or conversations associated with
the trauma
(2) efforts to avoid activities, places, or people that arouse recollections of
the trauma
(3) inability to recall an important aspect of the trauma
(4) markedly diminished interest or participation in significant
activities
(5) feeling of detachment or estrangement from others
(6) restricted range of affect (e.g., unable to have loving feelings)
(7) sense of a foreshortened future (e.g., does not expect to have a normal
life span)

posttraumatic stress disorder (continued)
D. Persistent symptoms of increased arousal (not present before the trauma), as
indicated by two (or more) of the following:
(1) difficulty falling or staying asleep
(2) irritability or outbursts of anger
(3) difficulty concentrating
(4) hypervigilance
(5) exaggerated startle response
E. Duration of the disturbance (symptoms in criteria B, C, and D) is more than
1 month.
F. The disturbance causes clinically significant distress or impairment in social,
Specify if:
Acute: if duration of symptoms is less than 3 months
Chronic: if duration of symptoms is 3 months or more
With delayed onset: if onset of symptoms is at least 6 months after the stressor
als, many of whom are uncomfortable with introspection and unfamiliar with
conventional terms for subjective states. In most cases, neurovegetative signs
and symptoms of mood disorder and the autonomic and psychomotor fea-
tures of anxiety disorder facilitate accurate diagnostic classification.
Schizophrenia With Anxiety
Although the characteristic hallucinations, delusions, thought disorder, and
bizarre behavior typical of schizophrenia and delusional disorder are clearly
not a part of uncomplicated anxiety disorder, elderly patients with these con-
ditions may be quite secretive about their psychotic experiences and can ap-
pear to have anxiety alone. Extra effort to establish rapport and develop the
patient’s trust can be very important in this situation; hospitalized elderly pa-
tients often connect with a particular staff member (usually on the night shift)
whom they trust and with whom they share their inner psychic content. If
doubt persists, projective psychological tests (e.g., the Thematic Appercep-
tion Test, the Rorschach Inkblot Test; see Chapter 3, “Mood Disorders—
Diagnosis”) can help to identify suppressed psychotic thought content. An-

other diagnostic challenge is confronted in the differentiation between obses-
sive thoughts (Simpson et al. 1999) and schizophrenic delusions. DSM-IV-
TR indicates that even when obsessions become ego-syntonic, “overvalued
ideas” (in which case the specifier “with poor insight” is applied), they remain
relatively vulnerable to challenge by evidence or logic (i.e., reality testing is in-
tact), allowing the clinician to distinguish them from manifestations of psy-
chosis (American Psychiatric Association 2000, p. 461).
Pathogenesis
The general psychodynamic literature on the pathogenesis of anxiety is too
voluminous to attempt to summarize here, although relatively little consider-
ation has been given to anxiety in late life. In addition to intrapsychic conflict
between libidinal impulses and emotions, the demands of conscience, and the
limitations imposed by circumstances, which are postulated to account for
anxiety throughout the life span, elderly individuals face anxiogenic circum-
stances unique to senescence. These include the growing discrepancy between
past and present capabilities, the increasing likelihood of mental and physical
incompetence, and the encroaching reality of death. Anxiety related to these
concerns may emerge directly into consciousness, wherein it can be relatively
easily identified, or may remain unconscious and be expressed indirectly as
somatic dysfunction, memory impairment, or nonspecific illness. In support
of this hypothesis, improved emotional well-being is often associated with in-
creased conscious awareness of, and ability to come to terms with, these as-
pects of aging (Gurian and Miner 1991).
Contemporary hypotheses about neurobiological substrates of anxiety and
fear focus on several interconnected subsystems of the central nervous system.
One subsystem is composed of noradrenergic innervation arising from cell
bodies in the locus coeruleus, a bilateral nucleus of cell bodies located in the
central gray matter of the isthmus on the floor of the fourth ventricle. Axons
from these cells provide the main noradrenergic input to the ipsilateral cortex,
cingulate gyrus, hippocampus, and cerebellum. They also impinge on cells in
the hypothalamus, thalamus, septal nuclei, and other subcortical structures,
where their influence is augmented by input from noradrenergic cells in the

lateral tegmental nuclei. Anatomical and pharmacological manipulation of
this system in animal models provides convincing evidence of its role in reg-
ulating aspects of cerebral arousal. This arousal is postulated to be experi-
enced as vigilance, anxiety, fear, or panic, in order of increasing intensity.
Hypothesized pathogenic influences on this system include genetic mecha-
nisms, early experiences, and the interaction of the two. Investigators theorize
that early experiences lead to structural and functional alterations in the re-
sponsiveness of this system, which ultimately lead to pathological states of
anxiety (Redmond 1987); moreover, studies of the noradrenergic system in
elderly subjects suggest that an age-related decrease in central noradrenergic
function may increase these subjects’ susceptibility to anxiety (Sunderland et
al. 1991).
More recent animal studies have examined the role of the medial prefron-
tal cortex–amygdala circuit in the pathogenesis of anxiety disorders, focusing
on dopaminergic input to the amygdala from the ventral tegmental area
(Gelowitz and Kokkinidis 1999) and lateralized serotonergic neurotransmis-
sion within the nondominant amygdala (Andersen and Teicher 1999). Find-
ings of these studies have been partially supported by clinical evidence of the
efficacy of serotonin reuptake inhibitors and dopamine receptor blockers in
anxiety disorders.
Another major area of investigation focuses on benzodiazepine receptors
localized to central neurons. These receptors appear to be linked to a “su-
pramolecular receptor complex” that includes a receptor for γ-aminobutyric
acid (GABA) (Hommer et al. 1987) and a chloride ion channel. Binding of a
benzodiazepine molecule to this receptor facilitates the ability of the GABA-
receptor complex to open chloride channels, allowing negatively charged
chloride ions to enter the cell and produce hyperpolarization, thereby reduc-
ing the cell’s reactivity to stimulation and its likelihood of conducting an im-
pulse. Autoradiographic studies have shown benzodiazepine receptors in
brain-stem structures, including the superior colliculus, the ventral nucleus of
the lateral lemniscus, and the substantia nigra, all of which, together with the
amygdala, constitute a component of the system that mediates the startle re-
sponse. This response has been extensively studied in animal models, and
pathological influences on its function have been postulated to underlie anx-
iety disorders in humans (Hommer et al. 1987). Evidence indicates that brain
levels of GABA are reduced in older subjects, which could result in an in-
creased propensity to anxiety with age (Sunderland et al. 1991).
Finally, a key role for serotonin receptors in the development of “normal”
anxiety behavior in humans has been delineated by Gross et al. (2002). They
noted that agonists of the serotonin type 1A (5-HT1A) receptor have anxiolytic
properties in both humans and animal models and that mice lacking this re-
ceptor (5-HT1A receptor knockout) show increased anxiety-like behavior in a
variety of conflict tests. The 5-HT1A receptor is expressed in two distinct neu-
ronal populations in the brain: as an autoreceptor on serotonin-containing
neurons of the raphe nuclei and as a heteroreceptor on nonserotonin-contain-
ing neurons of the forebrain (mainly the hippocampus, septum, and cortex).
Gross and colleagues used a tissue-specific and conditional 5-HT1A receptor
rescue mouse and found that restoration of the forebrain 5-HT1A receptor
alone was sufficient to reverse the anxiety-like phenotype of the knockout mice
and argued that this particular receptor population critically modulates anxi-
ety-like behavior. They also showed that receptor expression during the early
postnatal period is needed to establish normal anxiety-like behavior in the
adult. Despite these findings, no “unified” neurobiological theory of anxiety or
anxiety disorders in the elderly is widely accepted at this time.
Treatment
Psychosocial-Behavior Therapy
Although definitive studies in geriatric patients are lacking, there is little clin-
ical basis to doubt the efficacy of traditional psychotherapeutic approaches to
anxiety in the elderly. However, cost considerations often favor use of more fo-
cused, time-limited techniques such as cognitive-behavioral therapy (CBT),
which has been shown to be effective in nonelderly patients with anxiety dis-
orders, including OCD (Simpson et al. 1999), social phobia (Cottraux et al.
2000), and panic disorder (Barlow et al. 2000). The more purely behavioral
therapies are also preferred for reasons of cost and include relaxation tech-
niques aimed at generalized reduction of muscle tension and anxiety; desensi-
tization techniques that typically pair a state of induced relaxation with a real
or imagined feared situation or object; and graded exposure approaches that
attempt to extinguish anxiety, fear responses, or compulsive rituals gradually
by increasingly prolonged and intense exposure to feared situations.
A review by Mohlman (2004) of psychosocial treatment of GAD in the

elderly concluded that “the existing body of work does not clearly indicate the
superiority of CBT over alternative interventions [e.g., supportive therapy]”
(p. 149). The author noted that the modest results in a trial of CBT may be
related to learning difficulties in older patients and suggested that “age-appro-
priate principles of learning may need to be integrated to increase potency”
(p. 161). A recent well-controlled intervention randomly assigned older
adults with GAD to short-term (12-week) CBT, an active alternative psycho-
social treatment (a discussion group addressing anxiety-evoking themes), or a
wait-list condition. Patients who received active treatment showed clear im-
provements relative to those on the waiting list, with slightly greater benefit
observed with CBT compared with the discussion group. Reduction in anxi-
ety was clinically significant for one-third of the treated patients, and by 6-
month follow-up, one-half had achieved a high state of function, albeit with
some persisting anxiety. Effect sizes associated with treatment were somewhat
smaller than those that have been reported for CBT with younger GAD pa-
tients; however, the elderly participants in this study may well have been treat-
ment resistant because they had experienced anxiety for an average of more
than 30 years and almost 90% had tried other psychological or pharmacolog-
ical therapies. The authors noted that outcomes in some CBT groups were
better than in others, perhaps reflecting different levels of commitment and
skill among therapists (Wetherell et al. 2003a).
An Australian public health investigation of randomized controlled trials
for the general adult population compared efficacy and cost of different inter-
ventions for GAD and panic disorder, including CBT and several antidepres-
sants (Heuzenroeder et al. 2004). The conclusion was that CBT had greater
total health benefits than drug interventions alone for both anxiety disorders,
but limited access and variability in treatment delivery were noted as draw-
backs to systemwide provision of this therapy.
Successful treatment of a case of late-onset OCD with exposure and re-
sponse prevention was described by Carmin et al. (2002), but large-scale stud-
ies in the elderly remain to be published. In general, results with exposure and
response prevention are best when patients can clearly describe the situations
that provoke anxiety or ritualistic behavior. For patients whose anxiety is gen-
eralized or pervasive, techniques such as hypnosis, meditation, and guided
imagery may have a role. Although few outcome studies have been done, sig-
nificant reductions in subjective anxiety have been reported for elderly pa-
tients in response to both progressive and imaginal relaxation procedures
(Scogin et al. 1992). Following specific procedures for relaxation training
(Bernstein and Borkovec 1973) is important to ensure an effective interven-
tion and to compare results for a given patient with results of clinical investi-
gations. Several rating scales have been designed to assess the effectiveness of
relaxation interventions (Crist et al. 1989). Most therapists who use behavior
techniques in the treatment of anxiety advocate the adjunctive use of anti-
anxiety agents with behavior therapy; similarly, when phobic or obsessive-
compulsive behaviors emerge as part of a depressive syndrome, pharmacolog-
ical treatment of depression should be initiated before or during the applica-
tion of behavior therapy.
Psychopharmacotherapy
Benzodiazepines remain the treatment of choice for anxiety of acute or sub-
acute duration (Table 7–8). For very short-term anxiety associated with spe-
cific situations such as airplane travel, the longer-acting agents such as
diazepam can be used safely; when treatment is required on a daily or near-
daily basis for up to 4–6 weeks, such as in adjustment disorder with anxiety
or in acute GAD, daily use of the longer-acting agents in elderly patients will
lead to accumulation of clinically significant blood levels of long-acting active
metabolites, most of which have half-lives of several days or longer. Therefore,
in these situations, the shorter-acting benzodiazepines such as lorazepam or
oxazepam, which undergo single-step conjugation in the liver and have no ac-
tive metabolites, are generally preferable. These agents have the additional ad-
vantage of being relatively well tolerated by patients with even fairly advanced
liver disease. However, some elderly patients experience acute withdrawal
symptoms between doses of short-acting benzodiazepines; these symptoms
are severe enough to render these agents intolerable. In this situation, one au-
thor of this book (J.E.S.) has had excellent results with clonazepam, which is
long-acting but does not give rise to clinically significant amounts of active
metabolite, making it the only long-acting benzodiazepine free of this disad-
vantage. Typical dosages are 0.5–1.0 mg by mouth twice daily (Calkin et al.
1997).
Chronic GAD and the other anxiety disorders generally require continu-
ous therapy beyond 4–6 weeks, at which point the effectiveness of benzo-
Table 7–8. Pharmacological properties of benzodiazepines
Therapeutic
Rate of Duration Active Elimination dosage range
Drug Trade name absorption of action metabolites half-life (hours) (mg/day)a
Chlordiazepoxide Librium Intermediate Long Yes 5–30b 10–40

Diazepam Valium Fast Long Yes 20–50b 2–20
36–200b
Anxiety Disorders and Late-Onset Psychosis

Clorazepate Tranxene Fast Long Yes 7.5–30
Alprazolam Xanax Intermediate Intermediate Yes 12–15c 0.25–4
Lorazepam Ativan Intermediate Short No 10–14 0.5–6
Oxazepam Serax Slow Short No 5–10 15–60
Temazepam Restoril Slow Short No 10–20 15–90
Clonazepam Klonopin Fast Long Nod 20–50 0.5–3
aApproximate
range; some patients may require higher or lower dosages.
b
Approximately 100% longer in elderly (i.e., use high end of range), longer in men than in women.
cApproximately 50% longer in elderly.
dDominant metabolic pathway is nitroreduction, producing inactive metabolites; a minor oxidative pathway producing potentially active metabolites
also has been identified.

Source. Adapted from American Psychiatric Association: “Treatment With Antianxiety Agents,” in Treatments of Psychiatric Disorders: A Task Force
Report of the American Psychiatric Association, Vol. 3. Washington, DC, American Psychiatric Association, 1989, pp. 2036–2052. Copyright © 1989,
American Psychiatric Association. Used with permission.
291
diazepines may diminish and more reliable results may be obtained with
heterocyclic antidepressants such as nortriptyline, sertraline, paroxetine, ci-
talopram, escitalopram, mirtazapine, or venlafaxine. Dosages are similar to
those required for treatment of depression, and peak effects on anxiety tend
to occur sooner than peak antidepressant effects; otherwise, prescription fol-
lows the guidelines for treatment of mood disorder outlined in Chapter 4
(“Mood Disorders—Treatment”). Controlled trials in the elderly are scant;
Lenze et al. (2005b) administered citalopram, 20–30 mg/day, in a double-
blind, placebo-controlled, random-assignment design to 34 subjects (average
age=69.4). In each group, 15 subjects had GAD; the remaining 4 had panic
disorder (3) and PTSD (1). In the citalopram group, 11 of 17 responded,
whereas only 4 of 17 in the placebo group did.
Buspirone is another nonbenzodiazepine that has been shown to be an ef-
fective anxiolytic agent in elderly patients (Goldberg 1994). It has several ad-
vantages over benzodiazepines: no sedative effects, no interaction with alcohol,
and no tendency to produce dependence or withdrawal symptoms; therefore,
buspirone has little or no abuse potential. A disadvantage is that it has little or
no acute efficacy, and usually several weeks of daily dosage are required before
effects are observed. Buspirone is contraindicated in patients taking mono-
amine oxidase inhibitors (presumably because of its serotonergic properties)
and is less effective in patients who have been treated with benzodiazepines. In
general, neuroleptics have a very minimal role in the treatment of uncompli-
cated GAD, but Morinigo et al. (2005) reported excellent results with low-
dose risperidone (i.e., average dosage of about 1.3 mg/day) in a small study of
15 subjects (average age=74) with mixed anxiety disorders (including 10 with
GAD) who had failed treatment with other agents.
Treatment of panic disorder and OCD is somewhat more specific. Al-
though efficacy of alprazolam in nonelderly adults with panic disorder has
been reported, in general, benzodiazepines and buspirone are both relatively
ineffective in inhibiting panic attacks. Heterocyclic antidepressants (includ-
ing selective serotonin reuptake inhibitors, serotonin-norepinephrine re-
uptake blockers, and monoamine oxidase inhibitors) have been shown to be
effective in nonelderly patients, and one small, open-label study of 10 subjects
(average age =72.5) who had panic disorder, with or without agoraphobia,
found that 25–200 mg/day of sertraline (average dosage= 92.5 mg) elimi-
nated panic attacks in 9 of 10 subjects by the end of the 12-week study
(Sheikh et al. 2004a). Similarly, the adult literature has convincingly docu-
mented the efficacy of selective serotonin reuptake inhibitors for the treat-
ment of OCD, and although they are generally well tolerated and should be
effective in the elderly, definitive studies are lacking. Generally, dosages of an-
tidepressants are similar to those used for depressive disorders, and cautions
listed in Chapter 4 (“Mood Disorders—Treatment”) for treatment of depres-
sion apply.
Late-Onset Psychosis
Epidemiology
The prevalence of late-onset psychosis is difficult to estimate because of a lack
of diagnostic consistency across investigations. DSM-IV recognized the possi-
bility of late onset in all psychotic illnesses, including schizophrenia, delu-
sional disorder, mood disorder with psychotic features, substance-induced
psychotic disorder, and psychotic disorder due to a general medical condition.
Besides these “functional” disorders, DSM-IV also allowed dementia, includ-
ing Alzheimer’s type and vascular dementia, to be coded as “with delusions.”
(DSM-IV-TR, following ICD-9-CM [World Health Organization 1978]
convention, has a codable subtype of “with delusions” for vascular dementia
only.) In the National Institute of Mental Health Epidemiologic Catchment
Area Program (Regier et al. 1988), 0.1% of individuals age 65 or older were
given a diagnosis of schizophrenia with DSM-III (American Psychiatric Asso-
ciation 1980) criteria, which did not allow onset of schizophrenia after age 45.
Leuchter and Spar (1985) reported that first onset of psychosis after age 65
was recognized in 8% of 880 patients admitted to a university hospital–based
geropsychiatric unit. The diagnostic breakdown was as follows: 3.4% had or-
ganic mental disorder (mainly primary degenerative or vascular dementia)
with psychosis, 2.8% had mood disorder with psychosis, and 1.7% had disor-
ders that would be diagnosed by DSM-III-R (American Psychiatric Associa-
tion 1987) criteria as schizophrenia (10 of 15 patients) or delusional disorder
(4 of 15 patients). A similar diagnostic distribution was found by Webster and
Grossberg (1998), who reported on 1,700 consecutive admissions to a psycho-
geriatric unit. In their group, 10% had onset of psychotic symptoms after age
65, and the most common diagnoses were dementia of the Alzheimer’s type,
followed by major depression, medical or toxic causes, delirium, bipolar dis-

order, delusional disorder, schizophrenia, and schizoaffective disorder. The In-
ternational Late-Onset Schizophrenia Group (Howard et al. 2000), based on
extensive review of the literature, concluded that onset after age 40 of psy-
chotic symptoms typical for schizophrenia should be called late-onset schizo-
phrenia-like psychosis, and onset after age 60 should be called very-late-onset
schizophrenia-like psychosis (VLOSLP).
Risk Factors
Risk factors for development of VLOSLP include age (the incidence increases
by 11% with each 5-year increase in age [van Os et al. 1995]), female gender,
and ethnic minority immigrant status. British investigators found that the in-
cidence of VLOSLP was significantly higher in African- and Caribbean-born
elders than in indigenous elders (Reeves et al. 2001). Compared with early-
onset schizophrenia patients, patients with VLOSLP are less likely to have a
family history of schizophrenia, more commonly have sensory deficits (par-
ticularly conductive hearing loss), and less commonly have negative symp-
toms. Rodriguez-Ferrera et al. (2004) and Barak et al. (2002) found that
patients with VLOSLP had higher levels of education and were more likely to
be married than were members of a comparison group of early-onset schizo-
phrenia patients. Despite the age association, VLOSLP appears to be a stable
entity and not merely the harbinger of a progressive dementing condition, as
indicated by follow-up studies conducted by Mazeh and colleagues (2005),
Palmer et al. (2003), and Rabins and Lavrisha (2003).
Diagnostic Criteria
DSM-IV-TR diagnostic criteria for schizophrenia and delusional disorder are
summarized in Tables 7–9 and 7–10, respectively.
The clinical presentation of late-onset psychosis depends in large part on the
underlying diagnosis. Mood disorder with psychosis is described in Chapter
3 (“Mood Disorders—Diagnosis”), and dementia with psychosis is discussed
in Chapter 5 (“Dementia and Alzheimer’s Disease”); the typical picture of
VLOSLP follows DSM-IV-TR diagnostic criteria for schizophrenia: there are

schizophrenia
A. Two (or more) of the following, each present for a significant portion of time
during a 1-month period (or less if successfully treated):
(1) delusions
(2) hallucinations
(3) disorganized speech
(4) grossly disorganized or catatonic behavior
(5) negative symptoms, i.e., affective flattening, alogia, or avolition
Note: Only one Criterion A symptom is required if delusions are bizarre or
hallucinations consist of a voice keeping up a running commentary on the
person’s behavior or thoughts, or two or more voices conversing with each
other.
B. For a significant portion of the time since the onset of the disturbance, one or
more major areas of functioning such as work, interpersonal relations, or self-
care are markedly below the level achieved prior to the onset.
C. Continuous signs of the disturbance persist for at least 6 months, including at
least 1 month of symptoms (or less if successfully treated) that meet Criterion
A (i.e., active-phase symptoms) and may include periods of prodromal or
residual symptoms. During these prodromal or residual periods, the signs of
the disturbance may be manifested by only negative symptoms or two or more
symptoms listed in Criterion A present in an attenuated form.
D. Schizoaffective disorder and mood disorder with psychotic features have been
ruled out because either (1) no major depressive, manic, or mixed episodes
have occurred concurrently with the active-phase symptoms; or (2) if mood
episodes have occurred during active-phase symptoms, their total duration has
been brief relative to the duration of the active and residual periods.
F. If there is a history of autistic disorder or another pervasive developmental
disorder, the additional diagnosis of schizophrenia is made only if prominent
delusions or hallucinations are also present for at least a month (or less if
successfully treated).

delusional disorder
A. Nonbizarre delusions of at least 1 month’s duration.
B. Criterion A for schizophrenia has never been met.
C. Apart from the impact of the delusion(s) or its ramifications, functioning is
not markedly impaired and behavior is not obviously odd or bizarre.
D. If mood episodes have occurred concurrently with delusions, their total
duration has been brief relative to the duration of the delusional periods.
delusions that may be bizarre, hallucinations (which are more likely to be

visual than in early- or late-onset cases), and a relative absence of formal
thought disorder and affective blunting. The presentation of delusional
disorder similarly follows DSM-IV-TR, although hallucinations are non-
bizarre and functioning is relatively intact. However, the distinction between
VLOSLP and delusional disorder has been called into question by several in-
vestigators, most notably Riecher-Rossler et al. (2003), who studied hospital
case registers of more than 1,100 patients with schizophrenia or paranoid psy-
chosis, 352 of whom had onset after age 40. They concluded that “the validity
of the distinction between late-onset schizophrenia and other paranoid psy-
choses of old age would thus seem to be lacking at the descriptive as well as
the predictive and construct levels. Rather, there would appear to be a broad
overlap between the two diagnostic categories” (p. 602). Researchers in geri-
atric psychiatry seem to have agreed with this assessment, because published
articles on late-onset psychosis in recent years are essentially all focused on
VLOSLP, and the remainder of this chapter follows suit.
Most patients with schizophrenia spectrum disorders have neuropsychological
deficits, with severity ranging from mild frontal executive deficits to clinical de-
mentia. In a study of community-residing outpatients with schizophrenia
(Heaton et al. 2001), the average global neuropsychological score was 1.62 stan-
dard deviations (SDs) lower for patients compared with control subjects, and
about 30% of the patients had “very impaired” cognitive scores (>3 SDs below
the level of nonschizophrenic control subjects). Deficits of this magnitude con-
tribute in significant ways to the functional and social limitations associated with
schizophrenia-like conditions. However, in contrast to neurodegenerative disor-
ders such as Alzheimer’s disease and dementia with Lewy bodies, most studies
have found schizophrenia-related cognitive deficits to be stable over time. In the
Heaton et al. study, for example, mean changes over time and test-retest reliabil-
ities were the same for schizophrenic patients and control subjects across a wide
range of cognitive measures. Both older and younger patients had this stable pat-
tern. A related study compared performance on cognitive mental status exami-
nations (the Mini-Mental State Examination and Dementia Rating Scale; see
Chapter 5, “Dementia and Alzheimer’s Disease”) for older early-onset schizo-
phrenia spectrum patients, late-onset schizophrenia-like psychosis patients (on-
set after age 45 years), patients with Alzheimer’s disease, and control subjects
without mental disorders across retest intervals of 1–2 years. In this study, retest
scores also remained stable or even slightly improved for both early- and later-
onset schizophrenic-like disorder groups, whereas significant decline was noted
for patients with Alzheimer’s disease, with and without psychotic symptoms.
Longitudinal neuropsychological data for VLOSLP patients (e.g., age 75
and older) are scant, however, and more research is needed. Also, although
most cross-sectional studies have not shown excess rates of dementia among
patients with schizophrenia spectrum disorders when appropriate control
comparisons have been made, a few studies, mainly with older institutional-
ized samples, have found higher dementia rates. For example, in a retrospec-
tive chart review study (Dwork et al. 1998) that examined brain autopsy
findings for patients who had been institutionalized for severe mental disor-
der or dementia, a higher proportion of schizophrenic patients than those
with severe depression were rated as having significant cognitive impairment
prior to death (68% vs. 19%). The cognitively impaired schizophrenic pa-
tients had higher rates of Alzheimer-type brain changes (especially neocortical
neuritic plaques) than did those without cognitive deficit, but the extent of
these changes generally fell short of pathological criteria for Alzheimer’s dis-
ease. The investigators speculated that individuals with schizophrenia may
have lowered cognitive reserve, which predisposes them to clinically signifi-
cant cognitive changes at lesser levels of Alzheimer’s disease pathology.
The major diagnostic entities to be ruled out before diagnosing VLOSLP in-
clude mood disorder with psychosis and dementia with psychosis. Delirium,
particularly if induced by medications, also should be considered. In psy-
chotic mood disorder, sadness, dysphoria, anhedonia, and irritability are usu-
ally apparent enough to lead diagnostic efforts in the right direction; when
these features are obscured by psychotic manifestations, the diagnosis may
rest on identification of the characteristic neurovegetative signs and symp-
toms of depression and careful determination of a sequence of onset of symp-
toms in which mood and neurovegetative changes occur before delusions and
hallucinations. Late-onset hypomania and mania can present a clinical
picture very similar to that of VLOSLP (Spar et al. 1979). Again, correct di-
agnosis may require a detailed history obtained from multiple sources, in-
cluding medical records, along with inpatient observation. Dementia with
psychosis may be identified by mental status examination supplemented with
neuropsychological tests (see Chapter 5, “Dementia and Alzheimer’s Dis-
ease”). It is important to remember that performance on neuropsychological
tests may be impaired in the absence of organic brain disease if attention, con-
centration, and motivation are negatively affected by functional illness (i.e.,
pseudodementia). Accordingly, retesting after these symptoms are at least
partly controlled may avoid false-positive findings suggestive of degenerative
or vascular disease. Finally, delirium is rarely mistaken for VLOSLP, but med-
ications or combinations of medications that produce psychomotor slowing
and toxic hallucinations (e.g., low-potency neuroleptic medications with po-
tent central anticholinergic effects) can lead to this potentially hazardous
misdiagnosis.
Pathogenesis
Several plausible psychodynamic theories have been proposed to explain the
development of delusions in mental illness, although none has focused on
late-onset disorders. These hypotheses assume that delusions are “secondary,”
functioning to help maintain psychic equilibrium threatened by peculiar or
frightening experiences. For instance, the common delusion expressed by pa-
tients with dementia that people are stealing things from them becomes an
“explanation” for the disappearance and reappearance of items that are actu-
ally moved around by the patient, who has no recall of the events. The delu-
sion enables the individual to avoid the awareness of severely impaired
memory function. Similarly, mood-congruent delusions of bodily malfunc-
tion (“I can’t eat because the food doesn’t go into my stomach anymore”) and
delusional guilt (“The president has lost his veto power, and the Communists
are going to take over because of me”), commonly seen in psychotic major de-
pression, help the individual to explain and understand his or her pervasive
sense of dysphoria, degradation, and helplessness. In late-onset schizophrenia
and delusional disorder, in which intellectual deficits and mood disturbance
are absent, both internal and external stimuli for the development of persecu-
tory delusions have been described. Schwartz (1963) proposed that an inner
sense of meaninglessness or insignificance results in a self-aggrandizing delu-
sion of “centrality” (e.g., “The ill-intended actions of many other people are
oriented around me, so I must be a powerful and important person”). Arnold
(1999) proposed that in schizophrenia, a dysfunction in a “phylogenetically
old apparatus of a memory of situations” results in familiar perceptions being
experienced as novel, uncertain, vague, and alien. Psychic equilibrium is sus-
tained by explaining these changes as the results of the covert hostile actions
of others. Similarly, delusional beliefs often seem designed to explain halluci-
natory experiences; for example, “The neighbors are pumping poison gas into
my apartment” is a belief that might accompany olfactory hallucinations. Psy-
chodynamic explanations of hallucinations, catatonic behavior, and flat af-
fect, each of which is a feature of DSM-IV-TR schizophrenia, are generally
inadequately articulated in the literature.
Neurobiological explanations of delusions and hallucinations are partly based
on analogy with well-known drug-induced mental changes. The psychoses as-
sociated with long-term ingestion of dopaminergic agents such as amphet-
amine or cocaine have led to the hypothesis that “endogenous” dopaminergic
hyperactivity causes functional psychosis, whereas psychotic symptoms asso-
ciated with ingestion of serotonergic hallucinogens such as lysergic acid
diethylamide (LSD) have implicated serotonergic dysfunction. More recent
attention has been paid to the role of glutamate.
Hirsch and colleagues (1997) proposed that “schizophrenia and phen-

cyclidine psychosis are similar, and phencyclidine is known to block the
N-methyl-D-aspartate (NMDA) subtypes of glutamate (receptor). Moreover,
studies of messenger RNA [mRNA] suggest that glutamate receptor deficien-
cies occur in schizophrenia and are regionally and specifically distributed”
(p. 797). Hirsch and colleagues reported findings of 1) a marked decrease in
pyramidal cell dendritic spines in layer III of the frontal and temporal cortex
and 2) a correlation greater than 0.90 between decrease in mRNA for the
NMDA glutamate receptor and cognitive deterioration in elderly patients
with schizophrenia.
These findings support the hypothesis proposed by Glenthøj and Hem-
mingsen (1997), who observed that most abnormalities postulated to under-
lie schizophrenia “involve the cortico-striato-thalamo-cortical circuits, which
are central for attention and information processing” (p. 24). The authors
noted that
clinical and experimental studies point to a primary/early cortical defect

involving the glutamatergic system, and to a later developed intermittent
hyperactivity of the dopaminergic system superimposed on a basal hy-
podopaminergic state.. .. A changed neuroplastic response to environmental
stimulation due to dopaminergic sensitization can explain how an episodic,
subcortical hyperactivity can act on a basic glutamatergic and dopaminergic
hypofunction to produce psychotic symptoms. (p. 24)
Glenthøj and Hemmingsen present a hypothesis for spontaneous me-

solimbic dopaminergic sensitization and progressive evolution of psychosis
on the basis of their own clinical and experimental findings and those of oth-
ers—the “filter” hypothesis for schizophrenia and the state dependence of
schizophrenic symptoms. Other theorists have focused on structural abnor-
malities observed in the brains of schizophrenic patients (Harrison 1999), but
to date no widely accepted neurobiological theory of “functional” psychosis
has yet been articulated.
Treatment
Psychosocial-Behavior Therapy
Tarrier (2005) reviewed 20 controlled studies of CBT in schizophrenic patients
and found an overall effect size of 0.37 (SD=0.39), which is modest at best. He
concluded, “There is consistent evidence that CBT reduces persistent positive

symptoms in chronic patients and may have modest effects in speeding recovery
in acutely ill patients” (p. 131). Other reviewers (e.g., Turkington et al. 2004)
have emphasized the value of CBT as an adjunct to antipsychotic medications
and socially based remedial approaches such as social skills training. Although
none of the controlled trials in these reviews focused on elderly patients per se,
there is little reason to expect that CBT would be significantly less effective in
older patients, as long as cognitive impairment were not present. A randomized
controlled trial of cognitive-behavioral social skills training for middle-aged and
older outpatients (average age=approximately 54) with chronic schizophrenia
conducted by Granholm et al. (2005) found that
patients receiving combined treatment performed social functioning activi-

ties significantly more frequently than the patients in treatment as usual, al-
though general skill at social functioning activities did not differ significantly.
Patients receiving cognitive behavioral social skills training achieved signifi-
cantly greater cognitive insight…and demonstrated greater skill mastery. The
overall group effect was not significant for symptoms, but the greater increase
in cognitive insight with combined treatment was significantly correlated
with greater reduction in positive symptoms. (p. 520)
Rector and Beck (2002) described in detail how cognitive therapists con-
ceptualize and treat positive and negative symptoms of schizophrenia. The
Beck Cognitive Insight Scale (Beck et al. 2004), which measures the ability to
observe and question one’s own cognitive processes, provides a method for
tracking the cognitive effect of CBT or other therapies that has been validated
with older patients with psychotic disorders (Pedrelli et al. 2004).
Besides CBT, individual supportive psychotherapy aimed at building
trust, facilitating the flow of clinical data from the patient, and maximizing
compliance with somatic therapy can be an effective component of the overall
treatment program for VLOSLP. A recommended therapeutic stance toward
the patient’s delusional belief is “respectful disagreement,” wherein the thera-
pist does not claim to share the patient’s false belief but avoids confrontation
or argument with its content. Psychotic patients usually realize that others do
not agree with their beliefs, and they may become suspicious and distrustful
of the treating professional who does. However, open disagreement invites the
patient to incorporate the therapist into the delusion, thereby thwarting ef-
forts to establish a mutually respectful, trusting relationship. Although some

elderly patients are capable of a degree of detachment from their delusions
and can gain insight into their defensive function, insight-oriented psycho-
therapeutic approaches are usually discouraged in favor of approaches that fo-
cus on more dynamically superficial content, such as conscious concerns and
feelings. In this regard, psychotic patients often refuse to cooperate with treat-
ment aimed at the delusions or hallucinations per se, in which case the ther-
apy should be aimed at the accompanying anxiety, fear, sleeplessness, or
anhedonia.
Group therapy is generally of little value in the acute phase of psychotic
illness, although some patients can use the group situation to initiate social
contact with other patients and appear to benefit indirectly. Family therapy
may be extremely useful, particularly in situations in which family members
have been alienated by psychotic behavior. Although sessions without the pa-
tient can be productive, inviting the patient to participate each time may
avoid exacerbating feelings of mistrust and paranoia. Work with family mem-
bers focuses on education about the patient’s condition, the natural history
and prognosis of the disorder, and details of the treatment plan; the family
therapist also attempts to enlist family support for the inpatient and outpa-
tient components of the treatment plan.
Psychopharmacotherapy
Controlled studies are lacking, but Alexopoulos et al. (2004) surveyed 52
“American experts on treatment of older adults.” The experts’ first-line rec-
ommendation for late-life schizophrenia was risperidone (1.25–3.5 mg/day).
“Quetiapine (100–300 mg/day), olanzapine (7.5–15 mg/day), and aripipra-
zole (15–30 mg/day) were high second-line [choices]” (p. 5). Consistent with
these recommendations, several open studies have shown risperidone (David-
son et al. 2000; Madhusoodanan et al. 1999) and olanzapine (Madhuso-
odanan et al. 2000) to be effective and well tolerated in elderly patients with
psychoses. These agents’ main advantages over the typical antipsychotic med-
ications are their relative lack of extrapyramidal side effects, somewhat greater
efficacy for negative symptoms of schizophrenia, and somewhat lower pro-
pensity to impair cognition. Acute side effects of risperidone and olanzapine
are usually limited to sedation and orthostatic hypotension, and olanzapine
has anticholinergic effects that are usually well tolerated in therapeutic dosage
ranges. However, long-term side effects of significant weight gain, insulin re-
sistance and diabetes, and dyslipidemia are seen in varying degrees of severity
with all of the atypical antipsychotic agents. Accordingly, the experts surveyed
by Alexopoulos et al. (2004) would avoid clozapine, olanzapine, and conven-
tional antipsychotics (especially low- and mid-potency) for patients with dia-
betes, dyslipidemia, or obesity. Moreover, Alexopoulos et al. stated the
following:
Quetiapine is first line for a patient with Parkinson’s disease. Clozapine,

ziprasidone, and conventional antipsychotics (especially low- and mid-
potency) should be avoided in patients with QTc prolongation or congestive
heart failure. For patients with cognitive impairment, constipation, diabetes,
diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the ex-
perts prefer risperidone, with quetiapine high second line. (p. 5)
Of the typical antipsychotic agents, low-dose, high-potency medications

such as haloperidol and fluphenazine still have a role in VLOSLP, particularly
in patients whose symptoms are nonresponsive to the atypical agents or who
cannot tolerate the tendency of these agents to stimulate weight gain. Acute
side effects to be anticipated with typical agents include sedation, akathisia,
akinesia, and cogwheel rigidity. Adjunctive treatment with lorazepam or other
short-acting benzodiazepines often allows the total dosage of neuroleptic to
be reduced below levels that cause these side effects. One or two doses of an
antiparkinsonian agent such as benztropine or trihexyphenidyl hydrochloride
may be useful for diagnostic purposes when akathisia is suspected, but long-
term administration of anticholinergic agents should be avoided whenever
possible because of the increased susceptibility of elderly patients to memory
impairment, confusion, and anticholinergic delirium. Alternatively, clonaz-
epam, which produces no extrapyramidal side effects, may be effective in con-
trolling agitation and hallucinations but is typically less effective than
neuroleptic medications in reversing thought disorder and delusions. A typi-
cal starting dosage of clonazepam is 0.5 mg administered orally three times a
day, which can be increased up to threefold. At these dosages, side effects are
usually limited to sedation, but the risk of blood dyscrasia necessitates a pre-
treatment complete blood count followed by periodic retesting.
Dosages of atypical and typical antipsychotic medications required to
achieve symptom remission in VLOSLP typically range around 33%–100%
Table 7–11. Antipsychotic drugs, dose equivalences, and side-effect profiles

Equivalent dose Anticholinergic Extrapyramidal Hypotensive
Drug (mg/day) Sedation effects effectsa effects
Typical agents
Chlorpromazine 100 +++ ++ ++ +++ (im)
Thioridazineb,c 100 +++ +++ + ++
Perphenazine 8 ++ 0/+ +++ +
Trifluoperazine 5 + + ++ +
Thiothixene 5 + 0/+ ++ ++
Haloperidol 2 + 0 +++ 0/+
Fluphenazine 2 + 0/+ +++ +
Atypical agents
Risperidone 1.5 + 0 + +
Clozapined 100 +++ +++ 0/+ ++
Olanzapine 5 ++ ++ 0/+ +
Quetiapine 75 + + 0/+ +
Ziprasidonec 40 ++ + 0/+ +
Aripiprazole 15 + 0 0/+ +
Table 7–11. Antipsychotic drugs, dose equivalences, and side-effect profiles (continued)
Note. 0/+ =absent or very weak effect; += weak effect; ++= moderate effect; +++= strong effect; im=intramuscular.
aInclude acute dystonia, pseudoparkinsonism, akathisia, and perioral tremor (“rabbit syndrome”).
bMaximal dosage is 800 mg/day; higher dosages may cause pigmentary retinopathy.
c
Causes increase in QT/QTc interval; is contraindicated in patients with preexisting QTc interval>500 msec or various forms of cardiac illness.
dHypersalivation is common, especially at night.
Source. Adapted from Wise MG, Rundell JR: “Delirium (Acute Confusional States) and Dementia,” in Concise Guide to Consultation Psychiatry, 2nd
Edition. Washington, DC, American Psychiatric Press, 1994, p. 41. Copyright © 1994, American Psychiatric Press. Used with permission.
Anxiety Disorders and Late-Onset Psychosis

305
of the recommended dosage for schizophrenic adults. An effective dosage ti-

tration approach is to prescribe one-third to one-half the adult dosage on a
standing basis and to add a similar dosage on an as-needed basis once or twice
a day for agitation, hallucinations, or delusion-driven behavior (e.g., the pa-
tient will not eat because the food “comes from the toilet” or “is poisoned”).
Because delusional thought content may persist for weeks or months after de-
lusions are no longer driving the patient’s affect and behavior, it is usually im-
practical to use delusional thought content per se as a target symptom of acute
therapy. After acute symptoms subside, dosages can be gradually reduced un-
til symptom breakthrough occurs, at which point the dosage is increased
slightly and maintained. Table 7–11 presents dose equivalences and relative
side-effect potencies of the commonly prescribed atypical and typical anti-
psychotic medications.
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8
Other Common Mental Disorders
of the Elderly
Insomnia
Assessment
In addition to conducting thorough interviews of the patient and a sleep partner,
procedures that can be useful in establishing a diagnosis of insomnia include sleep
diaries, rating scales that assess sleep behaviors and related issues, and physiologi-
cal measures such as polysomnography. Trevorrow (1999) has provided recom-
mendations of topics to cover in a sleep assessment interview (Table 8–1) and a
description of sleep questionnaires and rating scales.
Almost half of the 29 million Americans age 65 and older complain of inad-
equate amount or quality of sleep (Monane 1992). The differential diagnosis
of insomnia in the elderly includes the conditions listed below.
Normal Aging Changes
In general, with advancing age, sleep becomes more fragmented, more time
is required to fall asleep, more awakenings occur, relatively less deep (Stage
IV) sleep is experienced, and people tend to spend more time in bed. The sub-
jective impression produced by these changes is unsatisfying sleep, which may
be reported as insomnia; it is not uncommon for elderly hospitalized patients
to report not sleeping at all, despite nursing observations of 6–8 hours of ap-
parent sleep, complete with snoring.
313
Table 8–1. Areas to consider in a sleep assessment interview

Nature of the complaint—what the problem is and when it occurs (e.g., sleep onset,
sleep maintenance, early-morning wake-up, daytime fatigue, nightmares)
Current sleep-wake schedule
History of sleep complaint (transient disturbance vs. long-standing complaint)
Symptoms of sleep disorders that may not be initially volunteered (e.g., restless legs,
periodic limb movements, narcolepsy, gastroesophageal reflux, parasomnias,
disruption of sleep-wake schedule)
Symptoms of sleep-disordered breathing (disturbed breathing at night, complaints
of snoring, headache on waking, partner sleeps in another room)
Daytime states, routines, activities (sleepiness, fatigue, functioning, mood, activities,
satisfaction with daily routines)
Naps (frequency, time of day, length)
Sleep hygiene (daytime activity, exercise, sleep environment, activity in bed, diet, use
of stimulants or depressants; see Table 8–3)
History of professional treatment of the sleep complaint and a review of what the
patient has tried to remedy the sleep problem
Medical or physical problems
Use of prescription and nonprescription drugs
Psychiatric history and mental status review (symptoms of depression, anxiety,
thought disorder, other psychological maladjustment)
Stressful circumstances (currently and when sleep problems began)
Information about antecedents, consequences, secondary gains, precipitating factors,
perpetuating factors
Source. Adapted from Trevorrow T: “Assessing Sleep Functioning in Older Adults,” in Hand-
book of Assessment in Clinical Gerontology. Edited by Lichtenberg P. New York, Wiley, 1999, pp.
331–350. Copyright © 1999 John Wiley & Sons, Inc. Reprinted with permission of John Wiley
& Sons, Inc.
Insomnia Associated With Axis I Psychiatric Illness

Sleep disturbance is associated with almost all of the major syndromes dis-
cussed in this book, including anxiety disorders, mood disorders, dementia
and delirium, psychosis, and adjustment disorder. The normal disruptions in
mental life caused by stressful or grief-producing situations must be added to
this list.
Other Common Mental Disorders of the Elderly 315
Insomnia Associated With Physical Illness

Physical conditions associated with pain (e.g., arthritis), with difficulty breathing
(e.g., congestive heart failure or chronic obstructive pulmonary disease), or with
immobility (e.g., stroke or Parkinson’s disease) can severely disturb sleep. Frequent
awakenings also may be associated with urinary obstruction secondary to prosta-
tism or chronic urinary tract infection. Sleep apnea has been found in about
30%–40% of elderly patients evaluated in sleep laboratories and is typically asso-
ciated with obesity and snoring. Nocturnal myoclonus, usually manifested as leg
twitches and jerks, is diagnosed somewhat less frequently and may be observed
without using sophisticated electronic equipment. Muscle movements that cause
brief awakenings are most likely to be indicative of this condition.
Substance-Induced Insomnia
Sympathomimetic agents (including decongestants and bronchodilators),
methylxanthine derivatives (such as theophylline and aminophylline), psy-
chostimulants, certain antidepressants (fluoxetine, bupropion, higher doses
of mirtazapine), and medications containing caffeine (as well as caffeine-
containing beverages such as coffee and many cola drinks) can interfere with
sleep, particularly if they are ingested late in the evening. Also, experimental
and clinical evidence indicates that most, if not all, hypnotic medications can
produce sleep disturbance after prolonged use (sometimes in as little as
3 weeks of nightly ingestion) or during the acute withdrawal phase after re-
peated ingestion (the so-called rebound effect).
Primary Insomnia
When the causes of insomnia listed above have been ruled out, the proper di-
agnosis is primary insomnia. DSM-IV-TR (American Psychiatric Association
2000) diagnostic criteria for primary insomnia are summarized in Table 8–2.
Treatment—General and Behavioral Interventions

In light of the differential diagnosis of insomnia described earlier in this section,
it is important whenever possible to treat mental and physical illness and to ad-
just the type, dosage, and timing of medications that can cause insomnia before
prescribing hypnotic agents. Of the physical illnesses that can disturb sleep, it is
particularly important to identify and treat breathing-related sleep disorder be-
cause taking sedative-hypnotic drugs can exacerbate this condition and create a
Table 8–2. Summary of DSM-IV-TR diagnostic criteria for primary

insomnia
A. The predominant complaint is difficulty initiating or maintaining sleep, or
nonrestorative sleep, for at least 1 month.
B. The sleep disturbance (or associated daytime fatigue) causes clinically
significant distress or impairment in social, occupational, or other important
areas of functioning.
C. The sleep disturbance does not occur exclusively during the course of
narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder,
or a parasomnia.
D. The disturbance does not occur exclusively during the course of another mental
disorder.
potentially lethal situation. Similarly, optimization of sleep hygiene should

always be attempted before hypnotic agents are prescribed for other than
occasional use. Table 8–3 lists the features regarded by The International Classi-
fication of Sleep Disorders (American Sleep Disorders Association 1997) as diag-
nostic of inadequate sleep hygiene. Interventions as simple as systematically
restricting time spent in bed and providing education about normal variability
in sleep patterns and age-related changes have been effective in increasing sleep
efficiency and reducing daytime sleepiness in older patients with insomnia
(Riedel et al. 1995). Modifying thoughts about “good” and “poor” sleep (e.g.,
8 hours of sleep per night is not necessary for everyone) is an example of a cog-
nitive-behavioral intervention that may also be useful in treating insomnia in
old age (Morin et al. 1993). A recent state-of-the-science conference (National
Institutes of Health 2005) on the manifestations and management of chronic
insomnia in adults concluded that a cognitive-behavioral treatment package is
“as effective as prescription medications are for brief treatment of chronic in-
somnia” (p. 8) and that “beneficial effects of CBT [cognitive-behavioral ther-
apy], in contrast to those produced by medications, may last well beyond the
termination of treatment” (p. 8). However, the review also pointed out that few
clinicians are trained in the use of CBT for chronic insomnia.
Table 8–3. Features of inadequate sleep hygiene

1. Daytime napping at least two times each week
2. Having variable wake-up times or bedtimes
3. Experiencing frequent periods (two to three times per week) of extended
amounts of time spent in bed
4. Routinely using products containing alcohol, tobacco, or caffeine in the period
preceding bedtime
5. Scheduling exercise too close to bedtime
6. Engaging in exciting or emotionally upsetting activities too close to bedtime
7. Frequently using the bed for nonsleep-related activities (e.g., television watching,
reading, studying, snacking)
8. Sleeping on an uncomfortable bed (e.g., poor mattress, inadequate blankets)
9. Allowing the bedroom to be too bright, too stuffy, too cluttered, too hot, too
cold, or in some way not conducive to sleep
10. Performing activities demanding high levels of concentration shortly before bed
11. Allowing mental activities, such as thinking, planning, and reminiscing, to
occur in bed
Source. Adapted from American Sleep Disorders Association: The International Classification of
Sleep Disorders: Diagnostic and Coding Manual, Revised. Rochester, MN, American Sleep Disor-
ders Association, 1997.
Treatment—Psychopharmacotherapy
Benzodiazepine anxiolytic and hypnotic medications and the nonbenzodiazepine
medications zolpidem, zaleplon, and eszopiclone (see Table 8–4) are the drugs of
choice for elderly patients with primary insomnia.
Benzodiazepine Hypnotics
Although Table 8–4 includes only three benzodiazepines that are specifically
marketed for inducing sleep, all agents of this class have hypnotic activity
and are essentially interchangeable, even though minor interindividual dif-
ferences in susceptibility to one or more of their effects are the rule. For oc-
casional use, almost any of the available agents are effective, but most elderly
patients will experience less morning “hangover” with the short-acting
agents, such as temazepam, lorazepam, or oxazepam, than with the long-act-
ing agents, such as diazepam or flurazepam. In this regard, alprazolam is in-
termediate in duration of action and in desirability, whereas triazolam is very
Table 8–4. Sedative-hypnotics, with dosage and duration of

action
Generic name (trade name) Dose (mg) Duration of action
Benzodiazepine hypnotics
Flurazepam (Dalmane) 15–30 Long
Temazepam (Restoril)a 15–30 Short
Triazolam (Halcion) 0.125–0.250 Ultrashort
Benzodiazepine anxiolytics
Lorazepam (Ativan)a 0.5–2 Short
Oxazepam (Serax)a 15–30 Short
Diazepam (Valium) 2.5–5 Long
Alprazolam (Xanax) 0.5–1 Intermediate
Barbiturates
Pentobarbital (Nembutal) 50–100 Intermediate
Secobarbital (Seconal) 50–500 Intermediate
Others
Chloral hydrate (many) 500–1,000 Intermediate
Glutethimide (Doriden) 25–250 Intermediate
Methyprylon (Noludar) 100–200 Intermediate
Zolpidem (Ambien)a 5–10 Short
Zaleplon (Sonata)a 5–10 Ultrashort
Eszopiclone (Lunesta)a 1–2 Short
a
Agents recommended for use in elderly persons.
short acting but should be avoided because of its propensity to cause ataxia,
paradoxical agitation, and mild but sometimes disturbing amnesia in some
elderly patients. For long-term use, the short-acting agents named above
(temazepam, lorazepam, or oxazepam) are much preferred over long-acting
agents (diazepam or flurazepam) because of the risk with the latter of build-
ing up potentially intoxicating blood levels of very long-acting active metab-
olites. The following case is illustrative:
A 76-year-old woman was admitted to the hospital for evaluation of mental

cloudiness and lethargy. Comprehensive medical and neurological workup
failed to identify a cause of her symptoms, and the fact that she had started
taking 5 mg of diazepam per night for sleep about 2 months before admission
was initially ignored. Subsequent consultation with a geriatric psychophar-

macologist led to discontinuation of the diazepam and rapid amelioration of
her symptoms.
Because benzodiazepine hypnotic agents begin to lose effectiveness after

several weeks of nightly ingestion, it is important to provide detailed instruc-
tions on their use, with emphasis on the advantages of irregular administra-
tion. Some clinicians attempt to avoid the development of tolerance by
prescribing two or three different benzodiazepines concurrently, with instruc-
tions to the patient to alternate between the medications weekly. Although
this approach has been successful in certain instances, no formal research data
supporting this practice have yet been published.
Nonbenzodiazepine Hypnotics
Three nonbenzodiazepine agents have been shown to be safe and effective for
elderly patients with primary insomnia: zolpidem (Shaw et al. 1992), zaleplon
(Hedner et al. 2000), and eszopiclone (R. Rosenberg et al. 2005; Zammit et
al. 2004). Each agent produces sleep by selectively binding to the γ-aminobu-
tyric acid (GABA)A1 receptor, and each is comparable to benzodiazepine hyp-
notics in terms of efficacy but produces somewhat less next-day drowsiness
and cognitive impairment. The nonbenzodiazepine agents, particularly es-
zopiclone, may be effective for longer than a few weeks, but definitive data
have not yet been published.
Zolpidem has a half-life of about 2 hours, has no active metabolites, and
does not accumulate during repeated administration. It has little anxiolytic or
anticonvulsant effect and causes few side effects beyond mild dizziness and
nausea. Studies of its effects on sleep architecture are equivocal, with some re-
porting minor increases in delta sleep. One study (Girault et al. 1996) sug-
gested that zolpidem is safe to administer to patients with chronic obstructive
pulmonary disease.
Zaleplon has a half-life of about 1 hour and also has no active metabolites
to accumulate. It is as effective as zolpidem and produces even less next-day
psychomotor impairment, although this may be largely because of its more
rapid elimination. Controlled studies have not identified any side effects in
excess of those produced by placebo, and “rebound” insomnia after the drug
has been eliminated has not been observed. Neither zolpidem nor zaleplon
has consistently shown sleep maintenance efficacy, as measured by wake time
after sleep onset, unlike the newest entry in the nonbenzodiazepine hypnotic
category, eszopiclone, which is a single-isomer cyclopyrrolone agent.
Eszopiclone is rapidly absorbed, with a time to peak concentration of ap-
proximately 1 hour and a half-life of 5–6 hours. It has been shown to produce
improvement in all four domains of insomnia—including sleep onset, sleep
maintenance, sleep duration, and restorative sleep—and studies in the elderly
suggest that it is safe and effective at dosages up to 2 mg/night.
Trazodone
Trazodone is not marketed as a hypnotic, but in low doses (i.e., 50–75 mg) it
is well tolerated and effective in inducing sleep and has the theoretical advan-
tage over several of the agents listed above of maintaining or actually increas-
ing delta sleep (Stages III and IV) (Scharf and Sachais 1990), which some sleep
researchers believe are the most refreshing stages of sleep. It has been shown to
be an effective hypnotic in patients with selective serotonin reuptake inhib-
itor–induced insomnia (Kaynak et al. 2004). However, trazodone, like the
benzodiazepine hypnotics, is associated with next-day somnolence and mild
impairment on some measures of cognitive function. It should also be noted
that insomnia remains an “off-label” (i.e., not approved by the U.S. Food and
Drug Administration), although widely recognized, indication for use of tra-
zodone.
Alcohol Abuse and Dependence

Epidemiology
The prevalence of alcohol abuse and dependence in community-dwelling
elderly persons ranges from 2% to 4% (Adams and Cox 1995) when DSM-
III (American Psychiatric Association 1980) criteria are used; less strict crite-
ria lead to higher estimates. Among primary care patients, the prevalence is
8%–15% (Oslin 2004), and surveys of hospitalized elderly persons and those
in nursing homes have produced prevalence estimates from 8% to around
50% (Johnson 2000). As the elderly population increases in the next decade,
the absolute number of older people with substance abuse problems will rise,
and because the currently middle-aged cohort has an increased incidence of
substance abuse, the frequency of problems among elderly persons is expected
to increase as well. The trend is already occurring: Grant et al. (2004) con-
trasted alcohol abuse prevalence rates from two comparable national surveys,
one done in 1991–1992 and the other in 2001–2002, and found a 4.8-fold
increase in the rate of alcohol abuse in people age 65 and older, from 0.25%
in 1991–1992 to 1.21% in 2001–2002.
All studies find that men are much more likely to be problem drinkers
than are women, and several patterns of relation to age at onset have been
identified. Most elderly alcoholic patients began drinking in young adult-
hood, but a significant proportion (up to 30%) do not develop a problem
with alcohol until late life.
Risk Factors
Risk factors for development of alcohol abuse or dependency in late life have
been difficult to pin down, but one survey (Moos et al. 2005) found that in-
creased health problems in elderly individuals predicted reduced alcohol con-
sumption but more drinking problems. The authors stated, “Older adults
with several health problems who consume more alcohol are at elevated risk
for drinking problems and should be targeted for brief interventions to help
them curtail their drinking” (p. 49).
Diagnostic Criteria
DSM-IV-TR distinguishes substance (alcohol) dependence, which is defined
in Table 8–5, from the generally less severe syndrome of substance (alcohol)
abuse, which is defined in Table 8–6.
Associated Psychiatric Conditions

Besides intoxication and withdrawal, the major mental syndromes associated
with alcohol abuse and dependence in the elderly are cognitive impairment
and depression. Cognitive impairment severe enough to meet DSM-IV-TR
criteria for dementia is common in active elderly drinkers but typically re-
solves during the first few weeks of abstinence as the acute effects of intoxica-
tion, poor nutrition, compromised liver function, and alcohol-induced mood
changes diminish. The proper diagnosis of cognitive deficits that persist in the
sober elderly alcoholic person may be challenging, but in clinical practice,
these deficits are often attributed to varying combinations of age-associated
memory impairment, Korsakoff-type amnesia (i.e., isolated short-term mem-
Table 8–5. Summary of DSM-IV-TR criteria for substance

dependence
A maladaptive pattern of substance use, leading to clinically significant impairment
or distress, as manifested by three (or more) of the following, occurring at any time
in the same 12-month period:
(1) tolerance, as defined by either of the following:
(a) a need for markedly increased amounts of the substance to achieve
intoxication or desired effect
(b) markedly diminished effect with continued use of the same amount
of the substance
(2) withdrawal, as manifested by either of the following:
(a) the characteristic withdrawal syndrome for the substance
(b) the same (or a closely related) substance is taken to relieve or avoid
withdrawal symptoms
(3) the substance is often taken in larger amounts or over a longer period than
was intended
(4) there is a persistent desire or unsuccessful efforts to cut down or control
substance use
(5) a great deal of time is spent in activities necessary to obtain the substance,
use the substance, or recover from its effects
(6) important social, occupational, or recreational activities are given up or
reduced because of substance use
(7) the substance use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been
caused or exacerbated by the substance
ory deficit), and underlying focal or diffuse vascular and/or degenerative

brain disease. Oslin and colleagues (1998) reviewed the literature on this
topic and proposed a set of research diagnostic criteria for “alcohol-related de-
mentia” (see Table 8–7), which they then validated in a later study of 192 in-
stitutionalized veterans (Oslin and Cary 2003). The 10.1% of the veterans
with dementia who met criteria for alcohol-related dementia were younger
(mean age=66.8 years) than those with Alzheimer’s disease, vascular demen-
tia, or mixed dementia (mean age= 74.7, 74.3, and 73.2 years, respectively)
Table 8–6. Summary of DSM-IV-TR criteria for substance abuse

A. A maladaptive pattern of substance use leading to clinically significant
impairment or distress, as manifested by one (or more) of the following,
occurring within a 12-month period:
(1) recurrent substance use resulting in a failure to fulfill major role obligations
at work, school, or home
(2) recurrent substance use in situations in which it is physically hazardous
(3) recurrent substance-related legal problems
(4) continued substance use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the
substance
B. The symptoms have never met the criteria for substance dependence for this
class of substance.
and, unlike subjects with Alzheimer’s disease, vascular dementia, or mixed de-
mentia, did not show declines in cognitive or physical functioning over a 24-
month follow-up period, during which they were abstinent from alcohol.
The relation between depressive symptoms and syndromes and alcohol
use and abuse is similarly complex. However, it is well established that depres-
sive symptoms are usually self-limited and spontaneously resolve if the elderly
individual is able to abstain for 3–4 weeks; persistent depressive symptoms
should be regarded as not directly related to the alcohol problem. Factors that
predict persistent depression include poor social support, major life problems
(both of which may be indirect effects of alcohol abuse), a history of depres-
sion or suicidality, and a family history of depression (Atkinson 1999).
Assessment
Accurate histories of alcohol use in adults can often be augmented by embed-
ding alcohol-related questions in the context of a general interview about
health behaviors. Several short questionnaires—for example, the CAGE
Questionnaire (Buchsbaum et al. 1992), the Michigan Alcoholism Screening
Test—Geriatric Version (Blow et al. 1992), the Alcohol Use Disorders Iden-
tification Test (AUDIT; Saunders et al. 1993), and the five-item AUDIT-5
Table 8–7. Classification of probable alcohol-related dementia

(ARD)
A. Criteria for the clinical diagnosis of probable ARD include the following:
1. A clinical diagnosis of dementia at least 60 days after the last exposure to
alcohol
2. Significant alcohol use, as defined by a minimum average of 35 standard
drinks per week for men, and 28 for women, for a period greater than
5 years. The period of significant alcohol use must occur within 3 years of
the initial onset of cognitive deficits.
B. The diagnosis of ARD is supported by the presence of any of the following:
1. Alcohol-related hepatic, pancreatic, gastrointestinal, cardiovascular, or
renal disease; that is, other end-organ damage
2. Ataxia or peripheral sensory polyneuropathy (not attributable to other
specific causes)
3. Beyond 60 days of abstinence, the cognitive impairment stabilizes or
improves.
4. After 60 days of abstinence, any neuroimaging evidence of ventricular or
sulcal dilatation improves.
5. Neuroimaging evidence of cerebellar atrophy, especially of the vermis
C. The following clinical features cast doubt on the diagnosis of ARD:
1. The presence of language impairment, especially dysnomia or anomia
2. The presence of focal neurological signs or symptoms (except ataxia or
peripheral sensory polyneuropathy)
3. Neuroimaging evidence of cortical or subcortical infarction, subdural
hematoma, or other focal brain pathology
4. Elevated Hachinski Ischemia Scale score
D. Clinical features that neither are supportive nor cast doubt on the diagnosis of
ARD include
1. Neuroimaging evidence of cortical atrophy
2. The presence of periventricular or deep white-matter lesions on
neuroimaging, in the absence of focal infarct(s)
Source. Adapted from Oslin and Cary 2003; Oslin et al. 1998.
(Philpot et al. 2003)—have been used to screen for problematic alcohol use.
Conigliaro and colleagues (2000) found each of these instruments to have
shortcomings when used in an elderly primary care population, and O’Con-
nell et al. (2004) reported that the CAGE Questionnaire “performed poorly
in psychiatric populations” but were more enthusiastic about the AUDIT-5,

which, they stated, “may prove more useful in older people with psychiatric
illness.”
Treatment—Brief Counseling and Psychotherapy

Simple advice and counseling provided by primary care physicians have been
shown to be effective in reducing problem drinking among high-risk (i.e.,
heavy-drinking) older adults (Fleming et al. 1999). In this study, two 10- to
15-minute counseling sessions resulted in a 34% reduction in 7-day alcohol
use, 74% reduction in mean number of binge-drinking episodes, and 62% re-
duction in the percentage of patients drinking more than 21 drinks per week
in the intervention group compared with the control group. The research lit-
erature generally suggests that treatment of established alcohol abuse and de-
pendence in the elderly follows principles appropriate for young and middle-
aged adults and depends on the severity of the problem, the financial and so-
cial resources of the patient, and the patient’s motivation. Combinations of
individual and group counseling, treatment of associated physical and mental
conditions, and referral to outpatient, partial hospital, and inpatient pro-
grams can be expected to result in outcomes as good as or better than in
younger individuals.
Treatment—Pharmacology
Oslin and associates (1997) studied a group of older veterans ages 50–70 years
in a double-blind, placebo-controlled randomized trial of naltrexone (50 mg/
day). The results were similar to those found with middle-aged adults: no im-
provement was seen in total abstinence, but half as many naltrexone-treated
subjects relapsed to significant drinking compared with those who received pla-
cebo. The medication was well tolerated and had few side effects beyond nausea
and dizziness. Acamprosate (calcium acetylhomotaurinate) is the newest phar-
macological agent approved for the treatment of alcoholism. It is a derivative of
the essential amino acid taurine and is structurally similar to GABA. Acam-
prosate is believed to enhance GABA neurotransmission and interfere with
glutamate action at the N-methyl-D-aspartate receptor. Bouza and colleagues
(2004) reviewed the research literature, which does not include any studies in
the elderly, and concluded that acamprosate was effective as adjuvant treatment
for alcohol dependence in adults and “appears to be especially useful in a ther-

apeutic approach targeted at achieving abstinence” (p. 811). Side effects are
minimal and include diarrhea, headaches, nausea, and pruritus. Disulfiram is
the best-studied agent for promoting abstinence but is seldom used in elderly
patients because of the risks of serious adverse reactions.
Other Psychoactive Substance Abuse and

Dependence
Epidemiology
Abuse and dependence (as defined in DSM-IV-TR) involving substances
other than alcohol appear to be quite rare in elderly individuals, but a pro-
spective, blinded observational study of patients age 60 years or older who
presented to a large urban emergency department over a 6-month period
found that 2% of these patients had positive urine test results for cocaine
(Rivers et al. 2004). Cocaine-positive patients were older, more frequently
male, and more than five times as likely to have alcohol or drug abuse diag-
noses as those with negative urine test results. This rate is three times higher
than the 0.6% rate for all illicit drug use in this age group estimated by the
National Household Survey on Drug Abuse (Substance Abuse and Mental
Health Services Administration 2001) and suggests that official surveys may
underestimate the actual prevalence of illicit drug use among the elderly.
More typical findings emerged from a study of 100 elderly patients hospi-
talized for substance abuse: female sex was a risk factor for drug dependence,
almost all cases involved sedative-hypnotics (primarily benzodiazepines), and
physical health problems involving chronic pain were common (Finlayson and
Davis 1994). This extreme version of a pattern of misuse has been termed non-
medical use and is defined as use of pain relievers, tranquilizers, stimulants, or
sedatives that were not prescribed for the individual, or use of the drug only
for the experience or feeling it caused (Zarba et al. 2005). According to a study
by Zarba et al. (2005), such use among those 65 or older declines in compar-
ison to those ages 50–64, but the likelihood increases among those who smoke
cigarettes and drink alcohol and is highest among older Americans who smoke,
drink, and use cannabis. The authors interpreted this finding as “carrying hab-
its into old age” because the association between cannabis use and other drug
abuse is also seen in young people. Other studies suggest that drug misuse
could affect as many as 14%–25% of elderly outpatients seen in psychiatric
settings (Jinks and Raschko 1990; Whitcup and Miller 1987). Medications
that are not in themselves psychoactive, and therefore not usually thought of
as abusable, may pose problems when they are combined with addicting sub-
stances. In this regard, acetaminophen-containing compounds, such as hy-
drocodone bitartrate–acetaminophen preparations. are of particular concern
because of renal (Elseviers and De Broe 1998) and hepatic (McClain et al.
1999) toxicity. Hepatic damage from long-term use may be severe; one author
of this book (J.E.S.) has consulted on several cases in which liver transplanta-
tion was necessitated by addiction to opioid-acetaminophen preparations.
Common Patterns of Abuse

Table 8–8 lists drugs that are abused or misused by elderly patients and that
should be inquired about in any suspect cases. In addition to simple overuse
or underuse of prescribed and over-the-counter drugs, the clinician should in-
quire about timing of drug ingestions, because significant problems could
arise from combining several agents in the following list:
• Benzodiazepine anxiolytics and antihistamines (additive sedation)

• Narcotic analgesics and antihistamines (additive sedation, constipation)
• Decongestants and caffeine (additive stimulation)
Distinguishing Use From Abuse

Distinguishing use from abuse is difficult in any age group, but it is particu-
larly challenging in elderly patients, which may partially explain why so many
cases—more than 95% in one study (McInnes and Powell 1994)—are over-
looked by physicians. Several of the factors discussed earlier regarding the
negative effects of alcohol apply here as well: 1) adverse consequences of med-
ication misuse such as falls, burns, generalized weakness, and sleep disturbance
may be misattributed to other medical conditions or may not be reported be-
cause of age-related memory impairment exacerbated by the effects of the
abused substance itself; 2) obvious mental status changes due to medication
abuse (e.g., somnolence, depression, poor attention and concentration) may
be ascribed to other causes (age, vascular or degenerative dementia, functional
Table 8–8. Psychoactive substances abused by elderly patients

Cold preparations containing anticholinergic antihistamines
Chlorpheniramine
Diphenhydramine
Cold preparations containing stimulating sympathomimetics
Ephedrine
Phenylephrine
Phenylpropanolamine
Pseudoephedrine
Narcotic analgesics
Codeine
Oxycodone
Propoxyphene
Nonnarcotic analgesics
Acetaminophen
Aspirin
Other nonsteroidal anti-inflammatory agents
Over-the-counter products containing caffeine or alcohol
Sedative-hypnotics
Barbiturates
Benzodiazepines
Chloral hydrate
Over-the-counter antihistamines
mood disorder); and 3) other negative consequences of substance abuse may

be disregarded entirely (e.g., symptom breakthrough caused by skipped doses
of medications prescribed for chronic physical illness, such as congestive heart
failure) or may be recognized but inappropriately considered an acceptable
side effect of or adverse reaction to an otherwise effective medication regimen.
Treatment
The key to treatment of substance abuse in elderly patients is preventing the
problem in the first place; Table 8–9 lists factors that Juergens (1994) recom-
mends physicians consider before prescribing potentially addictive medica-
tions to elderly patients. Recognition of the existence of a substance abuse

problem and the necessity of its treatment is also important: Brennan and col-
leagues (2001) found that fewer than 25% of elderly Medicare beneficiaries
whose substance abuse had been identified in the hospital obtained outpa-
tient treatment in the 4 years following hospital discharge. These researchers
suggest that treating professionals need to take an active role in follow-up
with these patients. Once substance abuse or dependence has been identified
and acknowledged, the specific approach is dictated by clinical circumstances.
Detoxification in the hospital is often the first step and should be considered
whenever drug effects are obvious and the precise identity of the drugs and
their dosages cannot be reliably ascertained. After detoxification, community-
based programs that incorporate home visits, individual and family counsel-
ing, recommendations for medication changes, and involvement in a peer
support or education group have been shown to be effective (Brymer and
Rusnell 2000) in reducing misuse of prescription medications. The clinician
should attempt to enlist the spouse, other family members, the patient’s other
physicians, and, when possible, the local pharmacist to help maintain surveil-
lance and control of availability of substances. Sponsors of nursing homes and
administrators at retirement hotels are often willing and able to assist in this
manner as well, and a firm therapeutic alliance with the patient, in the context
of which are discussed the patient’s fears that his or her real or imagined symp-
toms will go untreated if abused substances are not available, can be extremely
important and may in itself obviate the need for specific intervention.
Sexual Dysfunction
Sexual Dysfunction Versus Normal Aging Changes

In general, the diagnosis of sexual dysfunction is based on reduced function
in one or more of the first three phases of the sexual response cycle:
1. The desire phase (DSM-IV-TR hypoactive sexual desire disorder)

2. The excitement phase (DSM-IV-TR male erectile disorder, female sexual
arousal disorder)
3. Orgasm (DSM-IV-TR male or female orgasmic disorder)
Table 8–9. Factors to consider before prescribing potentially

addictive substances for elderly patients
Do the diagnosis, distress, and disability warrant the drug use?
Have appropriate nonpharmacological therapies been used when indicated?
Have pharmacological agents with less potential for long-term problems and
dependence been used if appropriate (e.g., buspirone hydrochloride for anxiety
or nonopioid analgesics for pain)?
Is the drug yielding an acceptable therapeutic response with use of appropriate doses
(often lower in elderly than in younger patients), and, if not, have the diagnosis
and treatment been reconsidered?
Has the patient had other drug or alcohol dependence or abuse problems in the past
(a major relative contraindication to use of addictive drugs)?
Do any findings suggest addiction to the prescribed drug (e.g., hoarding of drugs,
uncontrolled dose escalation, or obtaining drugs from multiple physicians)?
Is other drug-related impairment evident (e.g., memory or psychomotor disturbance)?
Can a family member or significant other confirm the effectiveness of the drug as
well as the absence of impairment and addiction?
Would tapering the dose of the drug (after an appropriate trial) help determine
whether problems are related to the drug or whether further treatment is needed?
Source. Adapted from Juergens SM: “Prescription Drug Dependence Among Elderly Persons.”
Mayo Clinic Proceedings 69:1215–1217, 1994.
Because normal aging is associated with reduced function in all three areas,
particularly in men, diagnosis of the above sexual dysfunctions in elderly pa-
tients requires that the clinician take normal aging changes into account. The
Massachusetts Male Aging Study found that the probability of complete erectile
dysfunction tripled from 5% to 15%, and that of moderate erectile dysfunction
doubled from 17% to 34%, between ages 40 and 70 years. The probability of
minimal erectile dysfunction was constant at 17% throughout the age range,
however (Levine 2000). This study also surveyed changes in male sexual activity
over a 9-year follow-up period. The investigators reported consistent declines in
frequency of intercourse, frequency of erections, sexual desire, and satisfaction
with sex in all age groups, but the largest declines were in men ages 60–70 at
entry into the study (Araujo et al. 2004). Similar results were found in the Glo-
bal Study of Sexual Attitudes and Behaviors (Laumann et al. 2005). These data
indicated that as men age, they should expect that sexual desire will gradually
diminish, sexual arousal will take more time and more stimulation, erections
will be softer and not last as long, ejaculation may be diminished in vigor, and
orgasm may not occur during every episode of intercourse. Because of the nat-
ural lengthening of the plateau phase of arousal, premature ejaculation is some-
what less likely to occur late in life but can occur in men at any age. Despite
these age-related changes, in one survey, almost 74% of the married men older
than 60 reported being sexually active, with the percentage declining to 43% in
men older than 75 (Diokno et al. 1990).
Women may notice several changes with advancing age: reduced desire
for sex, less vaginal lubrication (which can contribute to the development of
the sexual pain disorders dyspareunia and vaginismus), reduced clitoral and
breast sensitivity, and reduced intensity of the muscular phase of orgasm (due
to reduced perineal muscle tone). The ability to have orgasm per se is more
inconsistently affected, with some reporting increased ease of orgasm with
age. Despite these possible problems, the Global Study of Sexual Attitudes
and Behaviors found that increased age among women was not reliably asso-
ciated with any sexual dysfunction except lubrication difficulties (Laumann
et al. 2005). This relative “immunity” to age-related problems notwithstand-
ing, the reported prevalence of sexual activity in older women is somewhat
lower than in elderly men and appears to be influenced more by the availabil-
ity of a secure partner (Mooradian and Greiff 1990).
Sexual Dysfunction and Physical Illness

One of the most common causes of physiological erectile dysfunction in men
is prostate surgery. Perineal prostatectomy is the most likely cause of impo-
tence, followed by retropubic prostatectomy and transurethral prostatectomy.
Nevertheless, about two-thirds of men remain potent after retropubic proce-
dures. Erectile dysfunction is also strongly associated with hypertension, hy-
perlipidemia, diabetes mellitus, ischemic heart disease, peripheral vascular
disease, and several other conditions, almost all of which increase in preva-
lence with age. Seftel et al. (2004) analyzed medical records of more than
272,000 men with erectile dysfunction and found that more than 60% of
those ages 65–85 had hypertension, more than 50% had hyperlipidemia,
about 25% had diabetes, and 6% had depression. About 13% had the triad
of hypertension, hyperlipidemia, and diabetes. The authors concluded that
“ED [erectile dysfunction] is a pathophysiological event that shares common
etiological factors with hypertension, hyperlipidemia, diabetes and depres-

sion” (p. 2344) and advised physicians to view erectile dysfunction as a clini-
cal marker for detecting and treating these conditions at an early stage.
Sexual Dysfunction and Medications

The worst drug offenders vis-à-vis sexual dysfunction appear to be antihyper-
tensive medications, particularly guanethidine, methyldopa, clonidine, and the
β-blockers, all of which can impair erectile and ejaculatory function. Psycho-
pharmacological agents, including cyclic antidepressants and neuroleptics, also
have been implicated in erectile and ejaculatory dysfunction, and selective sero-
tonin reuptake inhibitors (see Chapter 4, “Mood Disorders—Treatment”),
monoamine oxidase inhibitors, and venlafaxine can also cause anorgasmia in
men and women. Sexual side effects of psychopharmacological agents are com-
mon in patients with severe mental illness and are a major cause of noncompli-
ance; often, patients are reluctant to discuss these side effects with their doctors
(K.P. Rosenberg et al. 2003). Trazodone has been reported in a relatively small
number of patients to cause painful and prolonged erection (priapism) that can
require surgical reduction and result in permanent damage. (Adverse medica-
tion effects are discussed more fully in Chapter 4.) Whether age is a risk factor
for these adverse effects is not clear, but a complete sexual history should address
the potential contribution of these agents, and dosage adjustment or replace-
ment should be attempted before more specific therapy is prescribed.
Treatment
Adjustment of offending medications, treatment of underlying physical and
mental illnesses, and optimization of general health are the treatments of first
choice for diminished libido and anorgasmia in elderly men and women.
When these steps are ineffective, treatment with testosterone may be effective.
According to a review by Bolour and Braunstein (2005),
testosterone therapy in the low-dose regimens is efficacious for the treatment

of low libido in postmenopausal women who are adequately estrogenized.
Clinical studies support the idea that androgens stimulate sexual desire and
satisfaction and demonstrate improved sexual enjoyment and well being in
women who switched from estrogen alone to estrogen–androgen therapy.
(p. 406)
The results of testosterone therapy in elderly men are somewhat more

complex. Studies in men with hypogonadism (Steidle et al. 2003) and erectile
dysfunction (Jain et al. 2000) have shown improvements in libido and erectile
function with testosterone therapy, but Gray et al. (2005), studying healthy
elderly men with experimentally manipulated testosterone levels, found im-
proved libido only in subjects who received high doses of testosterone and
who were sexually active at the beginning of the study. Total testosterone lev-
els were significantly correlated with changes in overall sexual function, wak-
ing erections, and libido but not correlated with changes in spontaneous
erections, intercourse frequency, or masturbation frequency. The authors
concluded “that testosterone supplementation in older men can dose-depen-
dently improve...libido and erectile function” (p. 3845). Testosterone ther-
apy for sexual dysfunction is not without risks, especially in men with
incipient prostate cancer, and is probably not within the range of expertise of
the typical geriatric psychiatrist.
Treatment of erectile dysfunction has been revolutionized by the phos-
phodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil. All
seem to be safe and generally effective in elderly men (Salonia et al. 2005). Hy-
pogonadism, cigarette smoking, and more severe erectile dysfunction at base-
line predict a poor response to sildenafil (Park et al. 2005), but testosterone
replacement enhances the response, at least in diabetic men (Kalinchenko et
al. 2003), and is likely to be effective in hypogonadal men as well. Smoking
cessation, although not studied, is another promising approach to suboptimal
response to sildenafil and probably vardenafil and tadalafil as well. In addition
to the precautions listed by the manufacturers, recent reports of the new onset
of nonarteritic anterior ischemic optic neuropathy (NAION), a type of blind-
ness in men taking phosphodiesterase-5 inhibitors, warrant additional caution
in those with preexisting NAION. Other risk factors are thought to include
tightly bundled nerves and blood vessels in the back of the eye (which are ap-
parently detectable via ophthalmoscopic examination), high blood pressure,
high cholesterol, and diabetes, all conditions common among elderly men.
Second-line treatment options for erectile dysfunction include intracaver-
nosal self-injection, a procedure that was the most common medical therapy for
erectile dysfunction before the approval of sildenafil. The patient injects a vaso-
active drug, such as alprostadil or prostaglandin E1, directly into the penis to
relax cavernous and arterial smooth muscle. Although response rates of up to
85% have been reported, the rate of treatment discontinuation is high, and side
effects include prolonged erection, penile pain, penile fibrosis, and hematoma
or ecchymosis. Because of the high dropout rate, a transurethral preparation of
alprostadil was developed that does not require needle injections into the penis.
In the medicated urethral system for erection, the patient uses a polypropylene
applicator to insert a semisolid pellet containing alprostadil into the urethra.
The medicated urethral system for erection produced erections sufficient for in-
tercourse in 65.9% of patients, and efficacy was similar regardless of age or the
cause of erectile dysfunction. The most common complaint was mild penile
pain, which was reported after 10.8% of alprostadil administrations in the
home setting and by 32.7% of men (Padma-Nathan et al. 1997).
The third-line intervention for treatment-resistant erectile dysfunction is sur-
gical implantation of a penile prosthesis. The three types of implants are semi-
rigid, positionable, and multicomponent inflatable. Each has advantages and
disadvantages, and consultation with a urologist experienced with these devices is
recommended. Treatment of erectile dysfunction is summarized in Table 8–10.
Psychiatric Illness Related to a General

Medical Condition
Personality Change Due to a General Medical Condition

Although personality changes are common in Alzheimer’s disease and vascu-
lar dementia and nearly universal in frontotemporal dementia, personality
change due to a general medical condition as defined in DSM-IV-TR is rela-
tively rare. DSM-IV-TR criteria for this syndrome are summarized in Table
8–11; note that the presence of delirium or dementia rules out this condition.
Koponen et al. (2002) diagnosed definite organic personality syndrome (by
DSM-III-R [American Psychiatric Association 1987] criteria) in 9 of 60 pa-
tients evaluated an average of 30 years after sustaining head trauma; another
5 had “subclinical” organic personality syndrome. Definite personality dis-
order that would have met DSM-IV-TR’s broader criteria for personality
change due to a general medical condition was diagnosed in another 14, for
an inclusive total of 28 of 60, or 47% of the sample. This prevalence is similar
to that reported by other investigators (Franulic et al. 2000).
Table 8–10. Assessment and treatment of erectile dysfunction

I. Diagnostic process
A. Sexual, medical, and psychosocial history
B. Physical examination
C. Laboratory tests
II. Consultation with patient and partner
A. Review findings
B. Determine patient and partner preferences
C. Educate about erectile dysfunction
III. Initial intervention
A. Change or discontinue offending medications
B. Replace hormones
C. Modify lifestyle
D. Corrective surgery
IV. First-line therapy, if above is ineffective
A. Oral agents (sildenafil, vardenafil, tadalafil)
B. Vacuum constriction devices
C. Couples therapy
V. Second-line therapy, if above is ineffective
A. Intraurethral alprostadil
B. Intracavernosal self-injection (alprostadil, prostaglandin E1)
VI. Third-line therapy, if above is ineffective
A. Surgical prosthesis
Source. Adapted from Process of Care Consensus Panel: “Position Paper: The Process of Care
Model for Evaluation and Treatment of Erectile Dysfunction.” International Journal of Impotence
Research 11:59–74, 1999.
Personality change due to a general medical condition without cognitive

impairment (per DSM-IV-TR) has also been described in Sydenham’s chorea
and in two prefrontal disconnection syndromes: 1) orbitofrontal syndrome,
in which limbic structures and orbital prefrontal cortex are damaged by, for
example, trauma, stroke, or tumor, and in which irritability, disinhibition,
and mood elevation are common; and 2) anterior cingulate syndrome, in
which the circuit connecting the anterior cingulate gyrus and ventral striatum
is involved, and in which apathy is common (Mega and Cummings 1994).
Although orbitofrontal syndromes may be classified as without cognitive def-

personality change due to a general medical condition
A. A persistent personality disturbance that represents a change from the
individual’s previous characteristic personality pattern.
B. There is evidence from the history, physical examination, or laboratory
findings that the disturbance is the direct physiological consequence of a
general medical condition.
C. The disturbance is not better accounted for by another mental disorder.
D. The disturbance does not occur exclusively during the course of a delirium.
E. The disturbance causes clinically significant distress or impairment in social,
icit by DSM-IV-TR criteria, impairments in everyday executive functions are

common (e.g., poor planning, monitoring, or completion of complex tasks),
reflecting the lability, impulsivity, and distractibility that characterize this dis-
order. These deficits may be less apparent on structured neurological or neu-
ropsychological examination than in natural problem-solving situations. If
midline brain structures are involved (orbitomedial frontal syndrome), mem-
ory deficits and problems with inhibition may be observed on careful testing.
Beneficial effects of behavioral interventions have been reported in some
patients with frontal lobe impairment; retraining of cognitive strategies is em-
phasized in mildly impaired patients, whereas altering the environment to re-
duce the need for self-initiation is emphasized in more severely impaired
patients (Sohlberg et al. 1993). In general, however, treatment of personality
change due to a general medical condition is aimed at amelioration of the spe-
cific medical condition judged to be causative in each case.
Psychotic Disorder Due to a General Medical Condition

Many general medical conditions have been identified as being capable of caus-
ing hallucinations or delusions. A review by Plotkin (1989) suggested that the
most likely general medical causes of delusions in elderly patients are cerebral
lesions associated with stroke or trauma, particularly if the temporal lobe and
limbic structures are affected. Pearlson (2000) argued that multiple infarctions
that do not necessarily cause dementia (“multi-infarct disease”) are associated

with late-life onset of schizophrenia. Whether this syndrome should be thought
of as a psychotic disorder secondary to a general medical condition or as late-
onset schizophrenia cannot be determined from the available data. Some spe-
cific delusion-like false beliefs also have been observed in patients with damage
to the occipital lobe (denial of blindness) and parietal lobe (denial of hemipare-
sis). Blindness and deafness have been associated with visual and auditory hal-
lucinations, and complex partial seizures have been associated with olfactory
hallucinations and delusions. Psychosis has been reported as a consequence of
vitamin B12 deficiency, meningioma, and antiretroviral therapy. Alcoholic hal-
lucinosis is a specific syndrome that occurs within 2–3 days after termination of
drinking. In this syndrome, frightening auditory or visual, sometimes tactile,
hallucinations occur in an otherwise clear sensorium and are typically accom-
panied by persecutory delusions.
The differential diagnosis of psychotic disorder due to a general medical
condition includes functional psychosis, dementia, and delirium. In most cases,
a complete medical evaluation will identify the general medical condition
judged to be etiologically related to the disturbance, allowing functional psy-
chosis to be ruled out. In dementia, cognitive disturbance will be present, and
in delirium, prominent deficits in attention and concentration, occasional frank
clouding of consciousness, and variable cognitive disturbance will be seen. In-
asmuch as sensory deficits have been cited as contributing factors in the devel-
opment of functional psychosis in elderly patients, the correct diagnosis of
psychosis with sensory loss may be difficult to establish with confidence.
Treatment of psychotic disorder due to a general medical condition is very
similar to treatment of mood disorder due to a general medical condition;
that is, potential endogenous causes are appropriately treated, and then ther-
apy for residual symptoms is administered according to the guidelines for
treatment of functional psychosis described in Chapter 7 (“Anxiety Disorders
and Late-Onset Psychosis”).
Chronic Pain
Half of the community-dwelling elderly and 60%–80% of those living
in nursing homes have been reported to have persistent pain complaints
(Schneider 2005); these complaints can be exacerbated by depression and
anxiety and can be applied consciously or unconsciously as a means to gain

attention and care. Therefore, proper management of chronic pain entails as-
sessment and manipulation of social support networks, recognition and treat-
ment of associated depressive and anxiety syndromes, physical therapy, and
pharmacological management (Schneider 2005).
Acetaminophen and tramadol, nonsteroidal anti-inflammatory drugs
(NSAIDs, particularly the selective cyclooxygenase-2 [COX-2] inhibitors),
topical agents, and opioids are the mainstay of pharmacological treatment of
chronic pain. Tramadol is a weak agonist of the mu opiate receptor and is in-
dicated for treatment of moderate to moderately severe pain. It has weak opi-
ate-like effects, blocks reuptake of norepinephrine and serotonin, may have
antidepressant properties (Rojas-Corrales et al. 2002), and has been reported
to produce serotonin syndrome in combination with selective serotonin re-
uptake inhibitors. Some clinicians are reluctant to prescribe chronic opioids
because of the fear of addiction, despite evidence that the great majority of
individuals who take opioids chronically for pain do not become addicted to
these drugs (even though physical dependency may develop) and evidence
that increased age is associated with reduced rate of development of tolerance
to opioid medications (Buntin-Mushock et al. 2005). Duloxetine, a mixed
norepinephrine and serotonin reuptake blocker, has been approved for the
treatment of chronic pain due to diabetic neuropathy, and evidence indicates
that other mixed norepinephrine- and serotonin-enhancing agents are also ef-
fective for neuropathic pain (Bomholt et al. 2005).
Some elderly patients can also benefit from behaviorally oriented pain
management training, including relaxation techniques (e.g., Ersek et al.
2003). Patients with no significant memory problems, with some insight into
the synergistic effects of mood state on pain, are good candidates for such in-
terventions.
It is not surprising that evidence suggests that elderly patients manage
chronic pain quite well with available agents and that chronic pain is not a
major determinant of the use of medical services (Cook and Thomas 1994).
However, when chronic pain is combined with depression, use of medical ser-
vices is increased, and persistent limitations in activities because of pain are
likely (Moosey and Gallagher 2004). Treatment of chronic pain in patients
with dementia poses several problems, not the least of which is the challenge
of assessing pain and its response to treatment when the patient is unable to
provide reliable information about the pain. Several visual analogue scales
have been shown to be useful in this situation (Pautex et al. 2005), and Rubey
(2005) provides a good overview of chronic pain management in elderly pa-
tients with dementia.
Influence of Aging on Disorders of Early Onset

Mood Disorders
As described in Chapter 3 (“Mood Disorders—Diagnosis”), some differences
in presentation of unipolar major depression in late life have been reported.
Elderly patients with bipolar disorder have been reported to have generally
less severe symptoms and less religiosity (Broadhead and Jacoby 1990), more
frequent and longer episodes, and more rapid cycling (Cutler and Post 1982)
compared with younger bipolar patients. However, Sajatovic et al. (2005)
found few differences in clinical characteristics between elderly patients with
early-onset and elderly patients with late-onset (i.e., after age 50) bipolar dis-
order, except that those with late-onset bipolar disorder were 2.8 times more
likely to be female.
Schizophrenia
Positive symptoms tend to diminish in aging schizophrenic patients, whereas
negative symptoms are more variable. Patients with schizophrenia have more
age-related decline in cognitive function than do age-matched control sub-
jects but much less than do patients with Alzheimer’s disease (Friedman et al.
2001). Bowie et al. (2005) reported that verbal productivity declines with age
and is correlated with worsening in Mini-Mental State Examination scores.
Kosmidis et al. (2005) used a word-list-generating task to distinguish phone-
mic word fluency from semantic word fluency (semantic=generate words in
a category—e.g., animals; phonemic= generate words starting with a particu-
lar letter—e.g., f) and found that the decline in elderly schizophrenic patients
was in phonemic and not semantic fluency. Bowie et al. (2005) concluded
that “thought disorder does not appear to ‘burn out’ in chronic schizophre-
nia” (p. 794). Some geriatric patients with schizophrenia may lose the skills
necessary to report symptoms, leading to the impression that their clinical sta-
tus is improving, but the trend among elderly schizophrenic patients seems to
be toward improved social adaptation (Cohen et al. 2000).
Personality Disorders
Agronin and Maletta (2000) reviewed the literature on personality disorders
in late life and found not more than “several dozen articles”; most were cross-
sectional prevalence studies in community and treatment populations that
used variable diagnostic criteria and inconsistent methodology, thereby allow-
ing few reliable generalizations. Studies that used structured interviews sug-
gested that the prevalence of personality disorders tends to decline with age
in community-dwelling subjects. However, personality disorders are as prev-
alent among elderly patients in geropsychiatric inpatient units as in a young
adult comparison sample (Ames and Molinari 1994; Molinari et al. 1994).
Studies typically report a higher prevalence of DSM-IV-TR Cluster C person-
ality disorders (avoidant, dependent, and obsessive-compulsive) among older
adults than either Cluster A disorders (paranoid, schizoid, and schizotypal) or
Cluster B disorders (antisocial, borderline, histrionic, and narcissistic) (Kunik
et al. 1994). Personality disorder as a comorbid condition appears to be sig-
nificantly more common in patients hospitalized for depression than in those
hospitalized for disorders of cognition (Kunik et al. 1994), and older de-
pressed patients with personality disorder have more persistent declines in
function and quality of life despite treatment (Abrams et al. 2001).
Regarding the natural history of personality disorders, Agronin and Mal-
etta (2000) found that published studies generally agreed with the prognostic
scheme proposed by Solomon (1981), which claimed that
individuals with PD [personality disorder] characterized by affective and be-

havioral lability (antisocial, borderline, histrionic, narcissistic, avoidant, and
dependent) demonstrate less impulsivity and aggression and have a tendency
to improve in late life, but with depression and hypochondriasis as common
endpoints. On the other hand, individuals with PD characterized by overcon-
trol of affect and impulses (obsessive-compulsive, paranoid, schizoid, and
schizotypal) either remain the same or worsen in late life, and demonstrate
persistent characteristics of rigidity and suspiciousness. (p. 7)
A study by Engels et al. (2003), which found that “community residents

in the oldest age group reported more schizoid and more obsessive-compul-
sive characteristics compared to one or more of the younger age groups
(and)…older mental health patients showed more schizoid disorder charac-
teristics and fewer high-energy disorder characteristics compared to one or
more of the younger patient groups” (p. 447), provided further support for
Solomon’s scheme. For an excellent overview of the effects of personality fac-
tors on mental disorders in later life, see Seidlitz (2001).
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9
Competency and Related
Forensic Issues
The issue of competency arises in many contexts involving cognitively im-

paired elderly individuals. Health care providers may question the patient’s
ability to give informed consent for medical treatment or to make end-of-life
decisions regarding resuscitation and life support. Attorneys may become con-
cerned about future challenges to the provisions of wills, gifts, and trusts, and
concerned friends or relatives may recommend that durable powers of attorney
be executed or may contemplate guardianship or conservatorship.
In this chapter, we address the specific social contexts in which the geri-
atric psychiatrist is most likely to perform a contemporaneous or retrospective
evaluation of competency. The chapter covers decisional competency, undue
influence, competency to care for oneself and manage one’s finances, expert
consultation and testimony on competency, determination of competency to
drive, and elder abuse.
We first discuss decisional competency, or the ability to make an acceptably
rational and self-interested single decision at a particular point in time. The main
types of decisional competency are 1) to give informed consent for medical care,
347
2) to execute an advance directive, 3) to give informed consent for enrollment in

a research study, 4) to enter into (and be held accountable for) a contract (contrac-
tual capacity), and 5) to execute a will (testamentary capacity) or trust. Next we
discuss functional competency, or the ability to provide self-care (provide oneself
with food, clothing, shelter, and medical care) and manage one’s finances. Func-
tional competency entails multiple types of decisional capacity but adds the re-
quirement of executive function, including motivation, prioritization, planning,
and execution of goal-oriented sequences of behavior over time. (Note: For pur-
poses of illustration and discussion, this chapter refers to California law. Because
statutory and governing case laws differ considerably from state to state, readers
are strongly urged to check the law applicable to their jurisdiction.)
Decisional Competency
Competency to Give Informed Consent for Medical Care
Four components of decisional competency in the medical setting were dis-
tinguished by Appelbaum and Grisso (1988) and have been accepted by most
authors. The four components involve the ability to
1. Communicate a choice
2. Understand relevant information
3. Appreciate the situation and its consequences
4. Manipulate information rationally (i.e., “to reach conclusions that are
logically consistent with the starting premises. This requires both weigh-
ing the risks and benefits of a single option and the usually more complex
process of weighing multiple options simultaneously.” [p. 1636])
Decisional competency is only one of three equally important compo-

nents of informed consent for medical care. The President’s Commission for
the Study of Ethical Problems in Medicine and Biomedical and Behavioral
Research (1982) concluded that the patient must be provided with appropri-
ate information about the recommended medical intervention (the categories
of information required by California law are listed in Table 9–1) and that the
consent must be given voluntarily—that is, it cannot be a result of coercion
or threats (discussed in “Undue Influence: The Question of Voluntariness”
later in this chapter).
Competency and Related Forensic Issues 349
Table 9–1. Requirements of informed consent: what patients

must be told about a proposed treatment
The nature and seriousness of the illness, disorder, or defect that the person has
The nature of the medical treatment that is being recommended by the person’s
health care providers
The probable degree and duration of any benefits and risks of any medical
intervention that is being recommended by the person’s health care providers
and the consequences of lack of treatment
The nature, risks, and benefits of any reasonable alternatives
Source. Adapted from Cal. Prob. Code §813.
Informed consent is generally not required for the great majority of medical
interventions, which are performed on the basis of “simple consent,” usually
obtained at the time a patient engages a new physician or during the admis-
sion process (the “Terms and Conditions of Admission” typically include sim-
ple consent). Simple consent similarly requires that the patient be competent
and that the consent be voluntary but does not require the provision of a pre-
determined body of information to the patient by the physician. Neither in-
formed nor simple consent is required in an emergent situation, in which
significant harm would come to a patient (or to others, in the case of a violent
patient) if the intervention were delayed so that consent could be obtained.
Under these circumstances, the principle of implied consent applies: that is, the
physician may perform the intervention to which a reasonable, self-interested
patient would consent, given the opportunity. Similarly, if the patient is un-
conscious or otherwise incompetent to participate in the consent process, and
no substitute decision maker (e.g., guardian or conservator, attorney-in-fact
for health care, or, in some jurisdictions, next of kin) or advance directive is
available, the physician may administer appropriate emergency treatment un-
til the patient is able to consent. In California, a nonemergent situation in
which no competent decision maker is available requires a specific court order
for medical intervention (Cal Prob. Code §3201).
Competency to Execute an Advance Directive

Advance directives are legal instruments intended to ensure that appropriate
decisions regarding medical care are made when a patient becomes incompe-
tent to give informed consent. The Patient Self-Determination Act of 1990
(P.L. 101-508), which became federal law on December 1, 1991, mandates

that hospitals, nursing homes, and other health care organizations provide in-
formation to patients about availability and use of these instruments.
There are generally two types of advance directives: proxy directives, such
as the durable power of attorney for health care or health care proxy, and in-
struction directives, such as the living will. Durable power of attorney for
health care allows an individual (the principal) to authorize another person,
usually a family member or spouse (the attorney-in-fact or agent), to give or
withhold consent for medical care for the principal if the principal becomes
incompetent. Legally defined, a durable power of attorney is
a power of attorney by which a principal designates another his attorney in

fact and the writing contains the words, “This power of attorney shall not be
affected by disability of the principal,” or “This power of attorney shall be-
come effective upon the disability or incapacity of the principal” or similar
words showing the intent of the principal that the authority conferred shall
be exercisable notwithstanding the principal’s subsequent disability or inca-
pacity. (Uniform Durable Power of Attorney Act 1983, p. 3960)
Some states have enacted similar laws creating the health care proxy.
A living will is a document that is created by an individual when he or she
is of sound mind, specifying the limits of care to be given by health care pro-
viders if the individual “cannot make or communicate a choice regarding a
particular health care decision.” The version available through the American
Medical Association directs the attending physician to withhold or withdraw
treatment “when the treatment will not give me a meaningful quality of life”
and provides a choice of three levels of quality of life, including “permanent
unconsciousness,” “some consciousness and in an irreversible condition of
complete, or nearly complete, loss of ability to think or communicate with
others,” and “no more than some ability to think or communicate with oth-
ers, and the likely risks and burdens of treatment outweigh the expected ben-
efits.” It also has a section in which the individual can specify particular
treatments that he or she does not want, as well as particular preferences re-
garding treatment and the end of his or her life (e.g., the preference to die at
home), and a section containing instructions regarding organ donation.
There are clear advantages and disadvantages to both types of directives.
A proxy has much more flexibility than an “instructive” has, and a proxy can
respond to circumstances that may not have been anticipated by the princi-
pal. Conversely, a proxy also can betray the trust of the principal by making
decisions that the principal would not have endorsed. In some states, a living
will and durable power of attorney for health care or health care proxy can be
combined, resulting in an instrument that requires the attorney-in-fact or
proxy to follow the provisions of the living will and authorizes the exercise of
his or her judgment in circumstances not covered by the will.
Because advance directives are intended to be executed when the principal
is competent to give or withhold consent for medical care, one might think
that the standard for competency to execute an advance directive would be
the same as the standard for competency to consent to medical care. Yet Cal-
ifornia law states, “A natural person having the capacity to contract may exe-
cute a power of attorney” (Cal. Prob. Code §4120). However, different
standards for competency to execute an advance directive may obtain in other
states.
In a similar vein, the powers of the attorney-in-fact differ from state to
state. California law prohibits the attorney-in-fact from consenting to place-
ment in a mental health treatment facility, convulsive treatment, psychosur-
gery, sterilization, or abortion (Cal. Prob. Code §4722) and also prohibits the
attorney-in-fact from consenting to health care or consenting to the with-
holding or withdrawal of health care “necessary to keep the principal alive, if
the principal objects to the health care or to the withholding or withdrawal
of the health care. In such a case, the case is governed by the law that would
apply if there were no durable power of attorney for health care” (Cal. Prob.
Code §4724). This section appears to reflect the will of the California legis-
lature that individuals retain the authority to make end-of-life decisions, even
if they are incompetent to make other medical decisions.
Much has been written about the question of which rules should govern
the decisions of substitute decision makers such as attorneys-in-fact. The pre-
vailing view is known as the doctrine of “substituted judgment,” according to
which the substitute decision maker should act, as much as possible, in accor-
dance with the wishes, values, and goals of the principal. The alternative “best
interests” approach calls on the substitute decision maker to perform an “ob-
jective assessment of the burdens and benefits for this patient” as the basis for
his or her decision (Fellows 1998, p. 924). The court in a New Jersey case (In
re Conroy 1985) spelled out a three-step protocol for analyzing the patient’s
wishes: First, consider any statements or other directives made by the patient.
If these are not conclusive, then attempt to deduce the patient’s wishes from
his or her more generally held values, religious beliefs, and so on. Finally, if
these steps leave the issue in doubt, revert to what a person in the patient’s
situation might reasonably choose.
Competency to Consent to Enrollment in a Research Study

The considerations discussed earlier regarding competency to consent to
medical care generally apply to competency to consent to enrollment in a
study. Before an investigator can claim to have secured informed consent, the
subject must have been supplied with appropriate information, voluntary
consent must have been obtained, and the subject must have been considered
competent. In 1982, the President’s Commission clearly spelled out the dis-
closures required under ordinary circumstances (Table 9–2), and in 1996, the
U.S. Food and Drug Administration published an “exception to informed
consent” rule intended to govern research conducted in medically emergent
circumstances. In 1998, the National Bioethics Advisory Commission (cre-
ated by President Clinton in 1995) issued a lengthy report, with 21 recom-
mendations, entitled, “Research Involving Persons With Mental Disorders
That May Affect Decisionmaking Capacity,” but few recommendations were
adopted, and the Code of Federal Regulations now includes minimal lan-
guage aimed at protection of cognitively impaired subjects. Specifically, Title
45 (Public Welfare), Part 46 (Protection of Human Subjects), section 46.111
(criteria for Institutional Review Board [IRB] Approval of Research), (a) 3
states, “Selection of subjects is equitable. In making this assessment the IRB
should take into account the purposes of the research and the setting in which
the research will be conducted and should be particularly cognizant of the
special problems of research involving vulnerable populations, such as chil-
dren, prisoners, pregnant women, mentally disabled persons, or economically
or educationally disadvantaged persons,” whereas section (b) states, “When
some or all of the subjects are likely to be vulnerable to coercion or undue in-
fluence, such as children, prisoners, pregnant women, mentally disabled per-
sons, or economically or educationally disadvantaged persons, additional
safeguards have been included in the study to protect the rights and welfare
of these subjects” (italics added; original available at http://www.hhs.gov/
ohrp/humansubjects/guidance/45cfr46.htm#46.111).
Table 9–2. Disclosures required for research subjects

The fact that research is being performed and the purposes of the research
Reasonably foreseeable risks, reasonably expected benefits, and appropriate
alternatives
A statement about the maintenance of confidentiality
An explanation about possible compensation if injury occurs, in cases of research
involving more than minimal risk
Information about how the subject can have pertinent questions answered
A statement about voluntary participation, indicating that refusal to participate
involves no penalties or loss of benefits
Source. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical
and Behavioral Research 1982.
Competency to Enter Into a Contract or Make a Gift

The traditional view of contract versus property law distinguishes between
the “future orientation” of contracts and the “present orientation” of a gift,
but competency to enter into a contract and competency to give a gift during
one’s lifetime (inter vivos) are treated as essentially the same in contemporary
legal literature (Meiklejohn 1988–1989). Geriatric psychiatrists are likely to
confront the issue of contractual capacity in two situations: 1) when an indi-
vidual who has entered into a contract or made a gift (the grantor) attempts
to escape responsibility for the future performance demanded by the contract,
or to retrieve assets already transferred per the terms of the contract or gift, on
the basis of the claim that he or she lacked contractual competency at the
time; and 2) when the establishment of a conservatorship of estate (discussed
in “Competency to Care for Oneself and Manage One’s Finances” later in this
chapter) is under contemplation by a court because a proposed conservatee is
thought to be unable, on the basis of mental incapacity, to manage his or her
finances or resist fraud or undue influence. Although courts have the author-
ity to grant exceptions in specific cases, the establishment of a conservatorship
generally creates an irrebuttable presumption that the conservatee lacks con-
tractual and donative (but not testamentary) capacity (although California,
oddly, allows conservatees to marry). Definitions of contractual capacity vary
widely by jurisdiction. Restatement of the Law Second, Contracts 2d (American
Law Institute 1981) provides as follows:
A person incurs only voidable contractual duties by entering into a transac-

tion if by reason of mental illness or defect (a) he is unable to understand in
a reasonable manner the nature and consequences of the transaction, or (b)
he is unable to act in a reasonable manner in relation to the transaction and
the other party has reason to know of his condition. (p. 41)
California law states, “A person entirely without understanding has no

power to make a contract of any kind” (Cal. Civ. Code §38) and “A convey-
ance or other contract made by a person of unsound mind, but not entirely
without understanding, made before his incapacity has been judicially deter-
mined, is subject to rescission” (Cal. Civ. Code §39). The vagueness of these
sections is partially remedied by the next section: “A rebuttable presumption
affecting the burden of proof that a person is of unsound mind shall exist if
the person is substantially unable to manage his or her own financial resources
or resist fraud or undue influence” (Cal. Civ. Code §39). This statute provides
a partial remedy for situations in which an individual, typically elderly and
cognitively impaired, who qualifies for but has not (yet) been provided a con-
servator of estate has entered into an unwise contract (e.g., for unneeded
home improvements) because of impaired judgment. If it can be proved that
a conservatorship could have been established, the usual assumption that ev-
ery adult is competent for all legal purposes is reversed, and the other party to
the contract must prove that the elderly individual possessed contractual ca-
pacity (Hankin 1995).
When a claim of contractual or donative incompetency is adjudicated,
courts tend to give substantial weight to facts besides the degree of mental im-
pairment of the grantor, such as the substantive fairness (i.e., the terms of the
contract or gift, as opposed to the procedural fairness) of the transaction in
question. In other words, the fact that the grantor agreed to an obviously bad
deal may be regarded as evidence supporting the claim that the grantor was
incompetent.
Competency to Make a Will

Most states define testamentary capacity as the capacity to “understand the na-
ture of the testamentary act, understand and recollect the nature and situation
of his or her property, and remember and understand his or her relations to his
or her living descendants, spouse, and parents, and those whose interests are
affected by the will.” Some states require only one or two of these criteria to be
met, and many states require that “the testator [be] also free of…delusions or
hallucinations [that] result in the person’s devising his or her property in a way
which, except for the existence of the delusions or hallucinations, he or she
would not have done” (Cal. Prob. Code §6100.5). In general, if lack of testa-
mentary capacity is proved, the entire will or codicil (modification to an exist-
ing will) is invalid. Testamentary capacity is generally recognized as “only a
modest level of competence (‘the weakest class of sound minds’)” (Estate of
Rosen 1982), and legal presumptions relating to this competency have tradi-
tionally also helped to set the bar fairly low. Besides the general presumption
that the testator was competent at the time the will was executed, it has also
been stated that “when one has a mental disorder in which there are lucid pe-
riods, it is presumed that his will has been made during a time of lucidity” (Es-
tate of Goetz 1967). The trend of more recent cases, however, has been toward
increasing recognition that at least in the case of progressive illnesses, such as
Alzheimer’s disease and vascular dementia, once testamentary capacity has
been lost, it is unlikely to return, even for brief periods.
Despite the fact that testamentary capacity is a low standard, wills are vulner-
able to challenge if an aggrieved party can produce any evidence of mental im-
pairment in the testator, and a medical record containing the mere diagnosis of a
neuropsychiatric illness is almost always enough, all things else being equal, to en-
courage contestants to proceed. Although it is common knowledge among psy-
chiatrists that a diagnosis alone does not imply any particular level of intellectual
function or automatically determine the presence or absence of any type of com-
petency, many judges, attorneys, and juries are not in possession of this insight
and may need to be educated through expert testimony. In many will contests,
the allegation that the testator lacked testamentary capacity at the time the will
was executed is accompanied by the allegation that the will, or parts of it, is the
product of undue influence. Because testamentary capacity is such a low stan-
dard, and because prospective evaluation of the testator is rarely performed (and
if it is, it is almost always at the request of a competent testator or of his or her
anticipated beneficiaries), it is usually very difficult to prove that a testator did not
possess testamentary capacity at the precise moment that the contested will was
signed (executed). Accordingly, allegation of undue influence often proves to be
the stronger case for the contestant. Any part of a will that is proved to be a result
of undue influence is overturned, but the remainder remains valid if the will
without the influenced provisions still makes sense and the testator otherwise had
testamentary capacity. Undue influence is discussed later in this chapter.
Competency to Execute a Trust

Trusts are increasingly popular instruments with which to determine the dispo-
sition of one’s assets after death, and to that extent, a trust serves the same func-
tion as a will, and the relatively low standard for testamentary capacity should
apply. But even if that standard did apply, the testamentary standard of under-
standing the nature of the testamentary act would almost always require more in-
tact intellectual function for a trust than that required for a will because trusts are
generally more complicated than wills, with more, and more detailed, provisions.
Moreover, a will is simply a piece of paper with a set of instructions, whereas a
trust is a more abstract entity that requires relatively intact higher intellectual
functions to grasp. Some courts have differentiated the standards of competency
for trusts and wills on the basis of the fact that establishing a trust entails a step
in addition to merely signing a set of instructions: the creator of the trust must
also transfer his or her property to the trust. This act would seem to require con-
tractual or donative capacity, which is widely but not universally regarded as a
higher level of competency than mere testamentary capacity. (For example, in
Citizen’s National Bank v. Pearson [1978], the court stated, “Greater mental ca-
pacity is required to make a deed than is required to execute a will.”) Another
path to the same conclusion is the argument that because the trustee is endowed
with the authority to enter into contracts involving the trust assets, the creator of
the trust (who is usually the trustee) should possess contractual capacity.
Assessing Decisional Competency

Clinical Interview
The cornerstone of the assessment of decisional capacity is the clinical interview
with the subject. This interview should include discussion of the social, eco-
nomic, and, if appropriate, medical circumstances surrounding the decision at
issue (i.e., who is affected by the decision, and how that party is affected); how
the subject arrived at the decision, including discussion of the role of other par-
ties (especially those affected by the decision); and what alternatives to the deci-
sion the subject recognizes. For example, the discussion of a proposed trust
amendment should include inquiry about what assets are entailed; how the
trustee(s), successor trustees, and beneficiaries were selected; and what events
and considerations led to the decision to amend the trust. The discussion of a
proposed medical intervention should cover the risks and benefits of the pro-
posed intervention and the most reasonable alternatives and should include in-
quiries of the subject that allow her or him to paraphrase and manipulate the
information provided and ask whatever questions that arise. By the end of this
discussion, it should be clear to the examiner whether the subject has the requi-
site understanding and appreciation of the consequences of the decision for the
subject and all others affected, the extent to which the decision was influenced
by interactions with others, how the decision comports with previously held val-
ues and goals, and whether delusional thinking affected the decision. The con-
clusion that the subject is or is not competent to make the decision at issue then
depends on what the examiner regards as evidence of minimally acceptable abil-
ity to “understand and appreciate,” “recall and recollect,” and so forth. That is,
does the examiner require that the subject produce key information from mem-
ory, either spontaneously or in response to inquiry, or is the ability merely to rec-
ognize information acceptable (e.g., a description of a parcel of real property or
of a proposed surgical procedure)? What level of detail is acceptable? How much
error is acceptable? This interrater variability in threshold accounts, in part, for
the often observed lack of agreement between examiners in published studies of
decisional competency (e.g., Marson et al. 1997; Vellinga et al. 2004) and for the
fact that equally qualified experts often provide conflicting opinions under oath.
Tests of Cognitive Function
To help mitigate the effects of the interrater variables described earlier, the ex-
aminer is advised to administer a battery of standardized tests of cognitive func-
tion along with the clinical interview. Impairment in other domains of mental
function (e.g., abnormal mood, anxiety, thought disorder) can, in principle,
negatively affect competency, but cognitive ability is the most consistent corre-
late of decisional competence (Palmer et al. 2005), and scores on tests of cogni-
tive function provide support for the examiner’s conclusions and allow the
cross-examining attorney and the trier of fact to place the expert’s opinion in
something approximating an “objective” context. One author of this book
(J.E.S.) routinely administers a Folstein Mini-Mental State Examination
(MMSE), a 12-item Boston Naming Test, general information items from the
Wechsler Adult Intelligence Scale, tests of remote memory (list the presidents,
describe key news events such as “What happened on 9/11/01?” and “What
was unusual about the 2000 presidential election?”), and tests of frontal execu-
tive function, including similarities, word-list generation, proverb interpreta-
tion, alternating design copying, and clock drawing. When indicated, this
battery is augmented with a “shopping list” test of new learning, tests of verbal
comprehension, and other more focused tests as indicated.
Standardized Tests of Decisional Competency
The literature on competency generally agrees that standardized tests have had a
limited role in competency determination, in part because of their inability to ad-
just to unique situational factors, including the consequences of the decision at is-
sue. As Grisso and Appelbaum (1998) indicated, the threshold for competence
should be adjusted according to the degree of harm associated with the subject’s
choice. For example, a lower level of understanding would be acceptable when a
patient is consenting to a medical procedure with a high benefit-risk ratio, as com-
pared with one that has a low ratio. Similarly, a lower threshold for concluding
that a testator has the ability to “understand and recollect the nature and situation
of his or her property” would be appropriate if there is only one natural heir, the
testator had no previous intention to leave the estate to anyone else, and the tes-
tator now intends to leave his or her estate entirely to that heir, as compared with
a situation in which a will contest is likely.
Several of the more recently developed standardized tests of competency al-
low the rater to adjust the threshold and may be useful as adjuncts to the clinical
interview. They include the MacArthur Competence Assessment Tool—Treat-
ment (Grisso et al. 1997) and the Competence Assessment Tool for Psychiatric
Advance Directives (Srebnik et al. 2004). These instruments assess a patient’s
capacity for understanding, appreciation, and reasoning by providing a body of
information and then requiring the patient to respond to questions about that
information. The result is several subscale scores that can be incorporated into
a competency determination.
Undue Influence: The Question of Voluntariness

As mentioned earlier, the question of undue influence is commonly raised in
conjunction with a claim of lack of testamentary capacity and in connection
with contested wills, contracts, and gifts. Susceptibility to undue influence is
also one of the criteria for establishment of a conservatorship of estate in Cal-

ifornia and some other states, and the underlying question of voluntariness is
also relevant to the issue of informed consent for medical care. Yet undue in-
fluence is a complex and poorly defined legal concept at best. In the legal lit-
erature, the question of undue influence tends to be reduced to the “will
substitution test”—that is, was the testator’s mind so controlled by another
person that his or her will is actually the will of another person? Depending
on the situation, this “will substitution” may require an element of “coercion,
compulsion, or restraint,” as in the testamentary context, or, with regard to
contracts, merely consist
1) in the use, by one in whom a confidence is reposed by another, or who

holds a real or apparent authority over him, of such confidence or authority
for the purpose of obtaining an unfair advantage over him; 2) in taking an
unfair advantage of another’s weakness of mind; or, 3) in taking a grossly op-
pressive and unfair advantage of another’s necessities or distress. (Cal. Civ.
Code §1575)
In some jurisdictions, the mere existence of a confidential and trusting re-

lationship, such as that between an elderly patient with psychiatric illness and
his or her primary caregiver, may be enough to shift the burden of proof to the
recipient, who then must prove that undue influence did not occur. The pre-
sumption of undue influence is strengthened if the donor is mentally weak; a
diagnosis of mental illness or retardation is generally adequate to support this
claim, and in some cases, even evidence that the donor is passive or manipulable
will suffice. The presumption of undue influence is also strengthened if the re-
cipient is a clerical, church, or spiritual adviser who fails to ascertain that a do-
nor has received competent and independent advice; if the recipient actively
procures the gift or bequest; or if the recipient unduly benefits from the gift or
bequest. A somewhat weaker set of factors are widely regarded as indicia (i.e.,
they serve to strengthen a claim of undue influence but do not, by themselves,
establish a presumption) of undue influence in a testamentary context. These
include “unnatural provisions in the will, provisions in the will that are incon-
sistent with prior or subsequent expressions of the testator’s intentions, and a
relationship between the testator and the beneficiary that created an opportu-
nity to control the testamentary act” (Spar and Garb 1992, p. 170). A diagnosis
of psychiatric illness in the allegedly influenced party will generally support a
claim of undue influence, but such a diagnosis is rarely more than just one con-
sideration of many. Singer (1992) identified six additional factors that “are
prominent in undue influence situations.” They are
the production of isolation, the creation of the ‘siege mentality,’ the fostering
of dependence, the creation of powerlessness, the use of fear and deception,
and keeping the victim unaware of the manipulative program put into place
to influence and control the person and to obtain the signing of documents
which benefit the manipulators at the cost of the signer. (p. 8)
These factors notwithstanding, it is important to remember that influ-

ence, even that which is clearly coercive, is not undue if it does not change the
preexisting disposition of the testator. That is, if the bequest or gift would
have been made anyway, absent the influence, then no undue influence has
occurred. Obviously, knowledge of the testator’s long-term wishes and inten-
tions is critical to the establishment of this defense.
Geriatric psychiatrists are likely to become involved in undue influence eval-
uations in the clinical setting when an individual is believed by friends or family
members to be vulnerable to exploitation and a conservatorship or guardianship
of estate is under consideration. A typical situation involves an elderly divorced
or widowed person with vascular or Alzheimer’s dementia who has fallen under
the sway of a much younger individual who has gradually taken over many care-
giving functions and, in some cases, has even become romantically involved with
the elderly person. Particularly if there is no close family, or if preexisting family
dynamics are distant or conflictful, it may be an easy matter for the younger per-
son to create several of the circumstances listed by Singer (1992). Naïve family
members may exacerbate the situation by opposing the relationship or by sug-
gesting that mental impairment is present, both of which responses may facilitate
the creation of the siege mentality. Inappropriate gifts, excessive payments for
services rendered, new trusts and wills, and even late-life marriages are typical re-
sults of this situation, especially if the patient has substantial assets.
Competency to Care for Oneself and Manage

One’s Finances
Laws exist in all 50 states and the District of Columbia providing for the ap-
pointment by a court of a guardian or conservator for persons found in-
competent to care for themselves or manage their finances. Criteria vary for
appointment of a conservator of a person (this conservator is called a guardian
in many states) and conservator of an estate (both conservator roles may be as-
sumed by the same person). This competency may be regarded as a form of
decisional capacity, at least in those states that use the Uniform Probate Code
(e.g., Alaska, Colorado, Montana), which defines an incapacitated individual
as someone who is “impaired by reason of mental illness, mental deficiency,
physical illness or disability, chronic use of drugs, chronic intoxication, or
other cause (except minority) to the extent that he lacks sufficient understand-
ing or capacity to make or communicate responsible decisions concerning his
person or which cause has so impaired the person's judgment that he is inca-
pable of realizing and making a rational decision with respect to his need for
treatment” (for an example, see http://data.opi.state.mt.us/bills/mca/72/5/
72-5-101.htm). However, in California, “a conservator of the person may be
appointed for a person who is unable to provide properly for his or her per-
sonal needs for physical health, food, clothing, or shelter” (Cal. Prob. Code
§1801a), and “a conservator of the estate may be appointed for a person who
is substantially unable to manage his or her own financial resources or resist
fraud or undue influence” (Cal. Prob. Code §1801b). Functional criteria such
as these subsume simple decisional capacity and, as mentioned earlier, add the
requirements of sustained motivation, judgment, and other executive func-
tions. Other than at the extremes of cognitive function (i.e., a perfectly normal
individual or one with severe, end-stage dementia), everyday function is diffi-
cult to predict from an office interview. Accordingly, the evaluation of the need
for a conservator of a person and/or an estate in California typically includes
interviewing individuals familiar with the proposed conservatee’s everyday
level of function; given that such informants are subject to bias and may them-
selves not be perfectly reliable (Wadley et al. 2003), multiple sources are desir-
able. In addition to this ancillary information, measures of frontal executive
function are also more critical in the assessment of these “downstream” func-
tions than are the simpler tests of language, memory, and comprehension that
are typically used in the assessment of decisional capacity (Brekke et al. 1997;
Chen et al. 1998).
In general, the powers of the conservator of person and the conservator of
estate are quite broad: the conservator of person has the power to make deci-
sions regarding place of residence and administration of medical care, and the
conservator of estate has the power to manage property, assets, and income
(this includes the power to enter into contractual arrangements on behalf of
the principal). In California, the conservator of person can consent to medical
care, but not over the objection of the conservatee, unless the court has
granted general or specific medical power—that is, the power to consent to
all medical care (general power) or to consent to a specific treatment (specific
power) even over the objection of the conservatee. The establishment of a
conservator of estate automatically renders the conservatee legally incompe-
tent to contract or to transfer property but does not establish lack of testa-
mentary capacity (i.e., the conservatee can still execute a will).
Conservatorship and guardianship are clearly radical solutions to the
competency problems occasioned by psychiatric and other illnesses. The pro-
cess of appointment of a guardian or conservator is often demeaning and
embarrassing to the conservatee, and disagreement over the need for conser-
vatorship and the motivations of those who support or resist it may lead to
long-lasting intrafamilial conflict and resentment. The appointment is also
expensive and time-consuming. In response to these shortcomings, most
states have provision for limited conservatorship and guardianship, wherein
only some of the powers discussed earlier are granted to the conservator, and
the rest remain with the conservatee, as determined by the court on a case-by-
case basis. But even this approach is costly and demeaning to the patient and,
despite court oversight, is sometimes conducive to fiduciary and even physical
abuse by guardians. And the process of adjudication of conservatorship and
guardianship itself has been criticized.
Guardianship petitions often recite minimal facts in support of the claim of

incompetence; often, in fact, they simply restate the circular and conclusory
language of the statutory definitions of incompetency. … Far too often,
[courts] are satisfied with only a perfunctory assessment of the alleged incom-
petent’s mental capacity.…Typically, evidence is limited to a brief letter from
a physician stating that the patient is incompetent. A complete psychiatric
evaluation and formal mental status exam are rarely included. (Rosoff and
Gottlieb 1987, pp. 15–16)
As if to document this claim, Armstrong (2000) has collected a series of

cases that poignantly illustrate the consequences of abuse of the conservator-
ship system. Clearly, alternatives to conservatorship and guardianship are de-
sirable, and fortunately several are available (Table 9–3).
Table 9–3. Surrogate decision-makers available to older persons in California
(may vary in other states)
Capacity necessary Survives Powers of agent Powers retained by
to establish incapacity or conservator individual Risks and recourse
Personal decision-
making
Durable power of Contractual Yes Makes medical May revoke DPAHC Agent may not make
Competency and Related Forensic Issues

attorney for health decisions when as long as competent, “substituted judgment”;
care (DPAHC) principal cannota may refuse medical court is recourse
care despite agent’s
consent
Living will Contractual Yes Specifies certain Not applicable May not anticipate all
limits of care situations, may not reflect
changed values
Probate None Yes May determine May refuse medical Conservator may not respect
conservatorship residence, make care, civil commitment conservatee’s values and
of person medical decisions (psychiatric wishes; court is recourse
(guardianship) hospitalization),
certain treatments
363

(may vary in other states) (continued)
Personal decision-
making (continued)
Probate None Yes May determine May refuse civil Conservator may not respect
conservatorship of residence, make commitment conservatee’s values and
person with general medical decisions (psychiatric wishes; court is recourse
medical powers hospitalization),
certain treatments
(e.g., psychosurgery,
abortion, sterilization)
Probate None Yes May determine May refuse civil Conservator may not respect
conservatorship residence, make commitment conservatee’s values and
for persons with medical decisions (psychiatric wishes; court is recourse
dementia hospitalization),
certain treatments
Mental health None Yes May consent to May refuse physical but Conservator may not respect
conservatorship mental health care not mental health care conservatee’s values and
of person only, including (including civil wishes; court is recourse
civil commitment commitment).
(may vary in other states) (continued)
Financial decision-
making
Power of attorney Contractual No May expend funds, May revoke as long as Principal must monitor use
Competency and Related Forensic Issues

contract competent of funds: court is recourse
Durable power of Contractual Yes May expend funds, May revoke as long as No oversight of use of funds
attorney contract when competent (“a license to steal”) since
principal cannota principal is incompetent:
court is recourse
Personal trusts Contractual to Yes Trustee can manage May modify as long as Trustee (if not the settlor)
establish, trust assets competent; some are may not respect settlor’s
testamentary to revocable values and wishes: court is
modifyb recourse
Probate None Yes May expend funds, May marry Variably reliable court
conservatorship contract oversight, yet court is only
of estate recourse
Mental health None Yes May expend funds, May contest most powers Variably reliable court
conservatorship contract of conservator of estate oversight, yet court is only
of estate recourse
365
a
Typically is a “springing power” that comes into effect after the principal becomes incompetent.
bAuthor
(J.E.S.) opinion.
Expert Consultation and Testimony on

Competency
Geriatric psychiatrists are particularly qualified to provide expert forensic con-
sultation and testimony regarding questions of competency and susceptibility
to undue influence. Accordingly, geriatric psychiatrists need to be familiar with
local statutes and case laws defining the various forms of competency. The psy-
chiatric expert may be asked to perform a contemporaneous evaluation of an
individual’s competency or susceptibility to undue influence or to state an opin-
ion on the competency and susceptibility to undue influence of an individual
who has since died. Guidelines for such evaluations in the testamentary context
have been published previously (Spar and Garb 1992) and are applicable to
each of the forms of decisional competency discussed in this chapter but are not
reviewed here. However, two revisions to those guidelines are suggested. First,
it is recommended that the medical expert avoid testifying on the issue of undue
influence per se, simply because undue influence is a complex finding that re-
quires the judgment that a particular benefit is “undue” or “unfair,” a judgment
that does not require medical expertise and is therefore not a proper part of ex-
pert testimony. In this regard, the only “expert” on the issue of undue influence
per se is the trier of fact, who hears all of the admissible evidence. Rather, med-
ical expert testimony should be restricted to the question of the presence and
severity of mental impairment and how the patient’s vulnerability to influence,
persuasion, manipulation, being taken advantage of, and so on is or would have
been affected by that impairment. If circumstances permit, testimony on
whether particular decisions made by the impaired individual are the direct re-
sult of such manipulation and persuasion also may be justified and may be per-
mitted. The second revision is based on Rule 703 of the Federal Rules of
Evidence, which states, in part, that
the facts or data in the particular case upon which an expert bases an opinion
or inference may be those perceived by or made known to the expert at or be-
fore the hearing. If of a type reasonably relied upon by experts in the partic-
ular field in forming opinions or inferences upon the subject, the facts or data
need not be admissible in evidence in order for the opinion or inference to be
admitted.
Rule 703 particularly applies when the psychiatrist’s expert opinion is based
on retrospective evaluation, which always depends on information derived from
sources other than the testator. Here it may be prudent to elicit testimony on di-
rect examination that clinical assessment and diagnosis of psychiatric illness in
the elderly are commonly reliant on information from sources (such as spouses,
relatives, caregivers, and medical records) other than direct examination of the
patient, especially if the patient is severely cognitively impaired, uncooperative,
mute, or catatonic. This explanation may be important testimony if the court is
inclined to believe, as some clearly are, that retrospective evaluation is not part of
reasonable clinical practice, is therefore not “protected” by Rule 703, and is of
highly questionable probative value. Anticipating and correcting this mispercep-
tion can be of great value in preserving the proper weight of expert testimony.
However it is performed, the expert role is substantially different from the
role of clinician, and somewhat different ethical principles pertain. The clini-
cian’s obligation to act in the best interests of the patient is replaced by the
consultant’s mandate to provide an honest and objective opinion and, in the
testimonial context, to express that opinion in a convincing manner. Because
the two obligations can easily conflict, it is usually not recommended for one
individual to assume both roles for the same patient.
Competency to Drive
The fraction of the American population that drives is rapidly aging, and it is
estimated that by the year 2024, one in four drivers in the United States will
be older than 65. Motor vehicle injuries are the leading cause of injury-related
deaths among drivers ages 65- to 74-years old and are the second leading cause
(after falls) among drivers ages 75- to 84-years old. Older drivers have a higher
fatality rate per mile driven than any other age group except drivers under age 25.
By age 80, male and female drivers are, respectively, 4 and 3.1 times more likely
than 20-year-olds to die as a result of a motor vehicle crash. On the basis of esti-
mated annual travel, the fatality rate for drivers 85 years and older is 9 times
higher than the rate for drivers ages 25–69 years old (Wang et al. 2003). Mul-
tiple age-related factors are likely to contribute to this phenomenon, including
declining visual and auditory acuity, effects of physical and neuropsychiatric
illnesses and their treatments, and declining decisional competence resulting
from slowing of cognitive processes and reaction time and deficits in attention,
concentration, and visuospatial and executive functions.
Available data are not adequate to determine the precise contribution of

each of these factors, but some generalizations are possible. Dementia clearly
increases the risk of crashing, even in the early stages of illness. Dubinsky et
al. (2000) reviewed the literature on behalf of the American Academy of Neu-
rology and concluded that drivers with early Alzheimer’s disease (MMSE
score between 19 and 25 or Clinical Dementia Rating [CDR; Morris 1993]
score of 1.0) had a relative crash risk “greater than our society tolerates for any
group of drivers,” and those with a CDR score of 0.5 (approximately corre-
sponding to an MMSE score of 25, according to Reisberg et al. [1994]) “have
an increased risk of accidents similar to that which society accepts for 16 to
19 year old drivers and for those drivers intoxicated with alcohol at a (blood
alcohol concentration) <0.08%” (p. 5). Dubinsky et al. issued a “practice pa-
rameter” stating that individuals with Alzheimer’s disease whose CDR score
is 1.0 or greater should not drive, and those with a CDR score of 0.5 should
be referred for a driving performance evaluation by a qualified examiner and
should be reassessed every 6 months.
Several investigators have examined the ability of various off-road assess-
ment tools to predict on-road driving ability of cognitively impaired elders.
Performance on tests of executive function, including mazes (Ott et al. 2003),
the Trail Making Test Part B (Uc et al. 2005), and clock drawing (Freund et
al. 2004), correlates with driving abilities in individuals with dementia, as
does performance on tests of visual attention and visuoperception. In partic-
ular, a measure called the Useful Field of View (UFOV), which refers to the
area of the visual field in which information can be rapidly extracted without
eye and head movements, appears to be of value in this context. Three com-
ponent functions contribute to the UFOV: speed of visual processing, ability
to divide attention, and ability to distinguish target from background; im-
pairments in each of these functions can result in diminished UFOV (Ball
1997; Ball et al. 1993). Reger et al. (2004) conducted a meta-analysis of the
literature correlating neuropsychological test performance with driving ability
and found that in studies that included a control group, the relation between
cognitive measures and on-road or nonroad driving measures was significant
for all reported domains, with mean correlations ranging from 0.35 to 0.65.
In studies without a control group, measures of visuospatial abilities were the
best predictors. In a study published since that review, the Driving Scenes test,
which is part of the new Neuropsychological Assessment Battery (Stern and
White 2003), was examined for its predictive value. It uses color drawings of
a road scene from the perspective of sitting behind the steering wheel of the
car and correctly classified 66% of the subjects into the three driving safety
categories of “safe,” “marginal,” and “unsafe.” It may have advantages over the
other tests discussed here in ease and convenience of administration and ac-
ceptableness to older adult examinees.
Physicians who make judgments about patients’ driving based on clinical
data appear to be comparably accurate at predicting the on-road performance
of patients with dementia. Ott et al. (2005) found that physician accuracy
(percentage of correct classifications) in categorizing patients as safe or unsafe
(as subsequently determined by on-road testing) ranged from 62% to 78%,
with the accuracy of the general practitioners ranging from 62% to 64% and
that of the dementia specialists ranging from 72% to 78%. Participating phy-
sicians based their predictions on almost 20 clinical variables, but those whose
predictions were most accurate placed more weight on duration of dementia,
measures of dementia severity (CDR and MMSE scores), and specific tests of
visuospatial ability, praxis, and executive function. In a similar study by
Brown et al. (2005), the single physician rater was an experienced neurologist
and specialist in dementia. His judgments, based on an extensive clinical in-
terview that included specific questions about any recent history of driving
problems, and the tests included in his diagnostic dementia evaluation were
74% accurate in predicting which patients would be classified as safe, mar-
ginal, or unsafe after an on-road driving test. In this study, the physician was
more accurate than either a family member “informant” or the patient in pre-
dicting driving safety. Subjects with very mild dementia (CDR score=0.5) or
mild dementia (CRD score=1.0) did not differ significantly in driving per-
formance, but both groups were significantly worse than control subjects
without dementia.
On-road evaluation remains the gold standard for assessing the safety of
drivers with dementia. Fitten et al. (1995) found that subjects with demen-
tia not only performed significantly more poorly on a driving test than did
control subjects but also committed more serious driving errors, particularly
during the more complex stages of the course. A. R. Dobbs (1997) studied
cognitively impaired seniors who were all still driving and observed three
types of driving errors. The most serious errors, which “could have resulted
in a crash had the driving instructor not taken control of the vehicle or the
traffic adjusted” (p. 10), were made almost exclusively by subjects with de-
mentia, and three of the four control subjects who made errors of this type
were subsequently determined, on the basis of cognitive testing, to have de-
mentia or other cognitive impairments. In this study, 25% of the subjects
with dementia showed driving competence within the range of the normal
drivers. Dobbs concluded that diminished driving competence among sub-
jects with dementia is most likely to be picked up by a test protocol (course
and scoring procedure) that focuses on the very serious errors that were most
discriminating in the experimental situation. Uc and colleagues (2005)
studied subjects with mild Alzheimer’s disease (average MMSE score= 26;
average age = 76.1 years) using several measures of cognitive function, the
UFOV, and visual acuity and then had subjects drive along a 1-mile stretch
of four-lane divided highway. The task was to identify and verbally report
traffic signs and restaurants along the route. Subjects with Alzheimer’s dis-
ease identified a significantly smaller percentage of restaurant and traffic
signs than did neurologically normal control subjects and made significantly
more at-fault driving errors.
Older drivers are at risk for other medical conditions that can impair driv-
ing ability. McCloskey et al. (1994) found that retinal disorders, macular de-
generation, myopia and presbyopia, and monocular vision, which all would
seem likely to increase crash risk, in fact did not. Glaucoma, however, was as-
sociated with an increased relative risk (odds ratio) of 1.5. Foley et al. (1995)
found that having cataracts severe enough to preclude reading a newspaper or
recognizing a friend across the street was associated with a relative risk of only
0.9, which did not reach statistical significance, and McCloskey et al. (1994)
found that hearing impairment did not increase crash risk, but wearing a
hearing aid while driving increased the risk of crashing by a relative risk of 1.9.
Koepsell et al. (1994) looked at stroke; coronary disease, including heart at-
tack, angina, and coronary surgery; chronic obstructive pulmonary disease;
cancer; asthma; osteoarthritis; rheumatoid arthritis; and diabetes and found
that only coronary disease in general (odds ratio=1.4) and diabetes (odds
ratio=2.6) were associated with increased crash risk.
Certain medications, as expected, are also important contributors to crash
risk. Ray et al. (1992) found that current use of benzodiazepines was statisti-
cally significantly associated with injurious crashes among older drivers in
Tennessee, at a relative risk of 1.5, whereas current use of cyclic antidepres-
sants was associated with a twofold increased risk. Foley et al. (1995) reported
the surprising finding that the use of opioids or antihistamines was not asso-
ciated with increased crash risk but use of nonsteroidal anti-inflammatory
agents was (relative risk =1.4).
Despite the evidence that dementia is a major contributor to crash risk,
as of this writing, few states have laws mandating that physicians report driv-
ers with dementia or other neuropsychiatric conditions that could impair
driving. In 2002, only 28 states had laws providing immunity for breach of
confidentiality for physicians who report medically unfit drivers.
Responding to evidence that a patient has become a dangerous driver may
be fraught with conflicts for the physician. A physician’s official report to au-
thorities of the patient’s impairment may result in an angry patient who
chooses another physician. Conversely, and more seriously, a physician’s deci-
sion not to report impairment may result in adverse legal consequences for
the physician. Physicians practicing in states with laws mandating reporting
of impaired drivers would seem somewhat better off in this regard, as would
physicians in states that do not provide immunity for a breach of confidenti-
ality. But every physician has the right and the obligation to attempt to con-
vince dangerously impaired drivers to stop driving, even if these admonitions
are not always effective. B.M. Dobbs (1997) found that 26% of the patients
evaluated as unsafe to drive continued to do so despite being instructed by
their physician to stop. Even here, though, there are conflicts of obligation,
because many patients perceive the loss of “the right to drive” as an intolerable
deprivation of autonomy and freedom, and the physician is obligated to pro-
tect the patient from that loss whenever it is reasonable to do so. But the phy-
sician is also obliged to protect the patient and others from the possible
consequences of the patient’s impairment. Improvements in the ability to pre-
dict dangerous driving on the basis of office evaluations are likely to exacer-
bate this aspect of the physician’s dilemma.
Elder Abuse
Epidemiological and clinical studies suggest that for every 100 older adults,
between 2 and 10 individuals are victims of abuse (Lachs and Pillemer 2004).
These figures may well be underestimates, because most cases are likely to go
undetected. In the National Elder Abuse Incidence Study, for example, 84%
of the cases were not reported to adult protective service agencies (Adminis-
tration on Aging 1998).
Elder abuse can occur in several forms, including the following generally
recognized categories:
• Physical—acts done to cause physical pain or injury

• Psychological—acts done to cause emotional pain or injury
• Sexual assault
• Material exploitation—including misappropriation of money or posses-
sions
• Neglect—failure to meet the needs of a dependent person
Neglect is by far the most commonly identified condition, including

many cases of self-neglect. In a study (Pavlik et al. 2001) of all allegations of
neglect in the state of Texas in 1997, 51% reflected general neglect (85% self-
neglect, 14% neglect by others) and 21% involved medical neglect, with the
remainder involving physical abuse, including sexual abuse (12%), exploita-
tion (8%), and emotional abuse (6%).
The risk of abuse increases sharply with age. In the Texas study, for example,
rates of reported elder abuse doubled with each 10-year increase in age (Pavlik
et al. 2001). Other factors that increase an older person’s risk for abuse include
dementia or other forms of cognitive deficit and a shared living situation, espe-
cially within a socially isolated family. Perpetrators of elder mistreatment often
have mental illness or alcohol abuse and may be dependent on the abused per-
son for material support (Lachs and Pillemer 2004). In about 9 of every 10 cases
of elder abuse, perpetrators are family members, and two-thirds of perpetrators
are adult children or spouses (Administration on Aging 1998).
The American Medical Association (1992) guidelines on elder abuse suggest
routine screening for family violence of all outpatients, and several screening tools
have been developed (for a review, see Fulmer et al. 2004). However, practitioner
surveys continue to indicate that physicians rarely do formal screening for elder
abuse and often do not inquire about this topic at all. After reviewing the domes-
tic violence literature, the U.S. Preventive Services Task Force (2004) declined to
endorse routine screening for elder abuse, in part because there have been no sys-
tematic investigations of the effectiveness of interventions for older adults who
have been victims of mistreatment. Nonetheless, there is widespread recognition
that all health care professionals need to be alert to the possibility of elder abuse
and to adopt methods for its detection in the United States and worldwide (Bon-
nie and Wallace 2002; World Health Organization 2002).
In their tutorial for physicians, Lachs and Pillemer (2004) emphasize the
need for in-depth but flexible examinations when elder abuse is suspected,
given the diverse forms and circumstances that may give rise to concern. In
the context of a comprehensive geriatric assessment, direct inquiries about
abuse and neglect are recommended, in addition to functional, cognitive,
physical, and social assessment. Psychiatrists and other physicians must be
able to differentiate normal aging changes and symptoms of disease from
signs of mistreatment and must be alert to both their own biases and those of
patients and family members with regard to acknowledging mistreatment.
Many older patients are reluctant to divulge abuse, and those with cognitive
impairment may be unable to recall or report their experiences. In most cases,
it is recommended that the patient be interviewed separately from caregivers
or family members whenever abuse is suspected. A home interview can also
yield valuable information.
Interventions for abused older adults need to be tailored to the symptoms
and situation. Medication to reduce agitation in an older person with demen-
tia may help to control triggers for abuse by a caregiver, or in the case of a
mentally ill perpetrator, treatment focused on the abuser may have the great-
est effect. Excellent case examples illustrating issues in intervention can be
found in a recent edited volume by Anetzberger (2004).
The National Center on Elder Abuse (http://www.elderabusecenter.org/)
provides links to bibliographies on detection and management of elder abuse,
as well as state-specific guidelines for case substantiation and reporting re-
quirements. Bergeron (2004) provides a thoughtful and practical discussion
of obligation to report issues for mental health professionals.
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Appendix
Clinical Assessment
Instruments
379
Geriatric Depression Scale

Choose the best answer for how you felt over the past week.
1. Are you basically satisfied with your life? yes/no
2. Have you dropped many of your activities and interests? yes/no
3. Do you feel that your life is empty? yes/no
4. Do you often get bored? yes/no
5. Are you hopeful about the future? yes/no
6. Are you bothered by thoughts you can’t get out of your head? yes/no
7. Are you in good spirits most of the time? yes/no
8. Are you afraid that something bad is going to happen to you? yes/no
9. Do you feel happy most of the time? yes/no
10. Do you often feel helpless? yes/no
11. Do you often get restless and fidgety? yes/no
12. Do you prefer to stay home, rather than going out and doing new things? yes/no
13. Do you frequently worry about the future? yes/no
14. Do you feel you have more problems with memory than most? yes/no
15. Do you think it is wonderful to be alive now? yes/no
16. Do you often feel downhearted and blue? yes/no
17. Do you feel pretty worthless the way you are now? yes/no
18. Do you worry a lot about the past? yes/no
19. Do you find life very exciting? yes/no
20. Is it hard for you to get started on new projects? yes/no
21. Do you feel full of energy? yes/no
22. Do you feel that your situation is hopeless? yes/no
23. Do you think that most people are better off than you are? yes/no
24. Do you frequently get upset over little things? yes/no
25. Do you frequently feel like crying? yes/no
26. Do you have trouble concentrating? yes/no
27. Do you enjoy getting up in the morning? yes/no
28. Do you prefer to avoid social gatherings? yes/no
29. Is it easy for you to make decisions? yes/no
30. Is your mind as clear as it used to be? yes/no
Appendix: Clinical Assessment Instruments 381
Geriatric Depression Scale (continued)

Critical responses:
“yes”: Items 2, 3, 4, 6, 8, 10, 11, 12, 13, 14, 16, 17, 18, 20, 22, 23, 24, 25, 26, 28
“no”: Items 1, 5, 7, 9, 15, 19, 21, 27, 29, 30
Scores ≥ 11 raise a question of depression.
Source. Yesavage J, Brink T, Rose T, et al.: “Development and Validation of a Geriatric Depres-
sion Screening Scale: A Preliminary Report.” Journal of Psychiatric Research 17:37–49, 1983. See
also Yesavage JA: “The Use of Self-Rating Depression Scales in the Elderly,” in Handbook for Clin-
ical Memory Assessment of Older Adults. Edited by Poon L. Washington, DC, American Psycho-
logical Association, 1986, pp. 213–217.
Six-Item Orientation-Memory-Concentration Test

Maximum
Item error Weight Score
What year is it now? 1 ×4 = _____

What month is it now? 1 ×3 = _____
Repeat this phrase after me: “John Brown,
42 Market Street, Chicago”
About what time is it? 1 ×3 = _____
Count backward from 20 to 1 2 ×2 = _____
Say the months in reverse order 2 ×2 = _____
Repeat the memory phrase 5 ×2 = _____
Total = _____
Note. One point is scored for each incorrect response and then multiplied by the weighing fac-
tor. Total weighted error scores > 10 suggest cognitive impairment.
Source. Adapted from Katzman R, Brown T, Fuld P, et al.: “Validation of a Short Orientation-
Memory-Concentration Test of Cognitive Impairment.” American Journal of Psychiatry 140:734–
739, 1983. Copyright 1983, American Psychiatric Association. Used with permission.
Appendix: Clinical Assessment Instruments
Cognistat profile of an 82-year-old woman with probable Alzheimer’s disease.
Note. ATT= attention; CALC= calculation; COMP= comprehension; CONST= construction; JUD= judgment; LOC = level of consciousness;
MEM= memory; NAM= naming; ORI= orientation; REP= repetition; SIM= similarities.
Source. Adapted from Northern California Neurobehavioral Group: Manual for Cognistat (The Neurobehavioral Cognitive Status Examination). Fairfax,
CA, Northern California Neurobehavioral Group, 1995, p. 12. Used with permission.
383
Instrumental Activities of Daily Living (IADL) Scale

A. Ability to use the telephone
Does not answer the telephone at all 1
Answers telephone but does not dial 2
Dials a few well-known numbers 3
Operates telephone on own initiative 4
B. Shopping
Completely unable to shop 1
Needs to be accompanied on any shopping trip 2
Shops independently for small purchases 3
Takes care of all shopping needs independently 4
C. Food preparation
Needs to have meals prepared and served 1
Heats and serves prepared meals, or prepares meals but does not maintain
an adequate diet 2
Prepares adequate meals if supplied with ingredients 3
Plans, prepares, and serves adequate meals independently 4
D. Housekeeping
Unable to participate in any housekeeping tasks 1
Needs help with all home maintenance tasks 2
Performs light daily tasks such as dishwashing 3
Maintains house alone or with occasional assistance 4
E. Laundry
All laundry must be done by others 1
Launders a few small items 2
Does most small items, depends on others for large items 3
Does personal laundry completely 4
F. Mode of transportation
Does not travel at all 1
Travel limited to taxi or automobile with assistance of another 2
Travels on public transportation when assisted or accompanied by another 3
Travels independently on public transportation, taxi, or drives own car 4
Instrumental Activities of Daily Living (IADL) Scale (continued)

G. Responsibility for own medications
Is not capable of dispensing own medication 1
Takes responsibility if medication is prepared in advance in separate dosages 2
Takes independent responsibility but occasionally forgets a dosage 3
Is responsible for taking medication in correct dosages at correct times 4
H. Ability to handle finances
Incapable of handling money 1
Manages day-to-day purchases but needs help with banking, major purchases,
etc. 2
Manages financial matters independently but, on occasion, has forgotten to
pay a bill or has been overdrawn in bank account 3
Manages financial matters independently, collects and keeps track of income 4
I. Ability to perform household repairs or chores
Unable to do even simple household repairs or chores 1
Can only do very simple tasks such as hanging a picture or mowing the lawn 2
With some help and direction can do moderately difficult household repairs
such as fixing a leaky faucet 3
Is able to independently perform most household chores or repairs 4
J. Skill in driving an automobile
Is unable to drive an automobile 1
Drives when someone is present to give directions, drives poorly, or drives very
slowly and cautiously 2
Drives alone but has some tendency to get lost or has occasional driving
problems 3
Drives alone, has good sense of direction, and good driving skills 4
Note. Items can be rated as “not applicable” for persons who have never performed a particular
activity (e.g., driving a car) or who have no opportunity to perform a particular activity.
Source. Reprinted from Lawton MP, Brody EM: “Assessment of Older People: Self-Maintaining
and Instrumental Activities of Daily Living.” The Gerontologist 9:179–186, 1969. Copyright
©The Gerontological Society of America. Reproduced by permission of the publisher.
Revised Memory and Behavior Problems Checklist

Instructions
The following is a list of problems patients sometimes have. Please indicate if any of
these problems have occurred during the past week. If so, how much has this bothered
or upset you when it happened? Please rate the frequency of the problem and your
reaction to it by circling a number from 0 to 9 for both frequency and reaction.
Frequency ratings
0=never occurred
1=not in the past week
2=1 to 2 times in the past week
3=3 to 6 times in the past week
4=daily or more often
9=don’t know/not applicable
Reaction ratings
0=not at all
1=a little
2=moderately
3=very much
4=extremely
9=don’t know/not applicable
Frequency Reaction
1. Asking the same question over and over 012349 012349
2. Trouble remembering recent events
(e.g., items in the newspaper or on TV) 012349 012349
3. Trouble remembering significant past events 012349 012349
4. Losing or misplacing things 012349 012349
5. Forgetting what day it is 012349 012349
6. Starting, but not finishing things 012349 012349
7. Difficulty concentrating on a task 012349 012349
8. Destroying property 012349 012349
9. Doing things that embarrass you 012349 012349
10. Waking you or other family members up at night 012349 012349
11. Talking loudly and rapidly 012349 012349
12. Appears anxious or worried 012349 012349
Revised Memory and Behavior Problems Checklist (continued)

Frequency Reaction
13. Engaging in behavior that is potentially
dangerous to self or others 012349 012349
14. Threats to hurt oneself 012349 012349
15. Threats to hurt others 012349 012349
16. Aggressive to others verbally 012349 012349
17. Appears sad or depressed 012349 012349
18. Expressing feelings of hopelessness or sadness
about the future (e.g., “Nothing worthwhile
ever happens,” “I never do anything right”) 012349 012349
19. Crying and tearfulness 012349 012349
20. Commenting about death of self or others (e.g.,
“Life isn’t worth living,” “I’d be better off dead”) 012349 012349
21. Talking about feeling lonely 012349 012349
22. Comments about feeling worthless or being a
burden to others 012349 012349
23. Comments about feeling like a failure or about
not having worthwhile accomplishments in life 012349 012349
24. Arguing, irritability, and/or complaining 012349 012349
Source. Adapted from Teri L, Truax P, Logsdon R, et al.: “Assessment of Behavior Problems in
Dementia: The Revised Memory and Behavior Problems Checklist.” Psychology and Aging
7:622–631, 1992. Used with permission.
Items Rated on the Neuropsychiatric Inventory

Item N/A Absent Frequency Severity
Delusions X 0 1234 123

Hallucinations X 0 1234 123
Agitation X 0 1234 123
Depression/dysphoria X 0 1234 123
Anxiety X 0 1234 123
Euphoria/elation X 0 1234 123
Apathy/indifference X 0 1234 123
Disinhibition X 0 1234 123
Irritability/lability X 0 1234 123
Aberrant motor behavior X 0 1234 123
Nighttime behavior X 0 1234 123
Appetite/eating change X 0 1234 123
Note. N/A =not applicable (e.g., caregiver does not appear to understand the item, or response
misleading for any reason).
Frequency: 1= less than once/week; 2 =about once/week; 3 =several times/week but less than
daily; 4= daily or continuously.
Severity: 1= mild; 2 =moderate; 3 =severe.
Source. Reprinted from Cummings JL, Mega M, Gray K, et al.: “The Neuropsychiatric Inven-
tory: Comprehensive Assessment of Psychopathology in Dementia.” Neurology 44:2308–2314,
1994. Used with permission.
Index
Page numbers printed in boldface type refer to tables or figures.
Abbreviated cognitive screens, 181–183 Age and aging. See also Age of onset;
Abraham, Karl, 108, 115 Older adults; Very old people
Acamprosate, 325–326 biological factors in, 48–61
Accidents, and motor vehicles, 367– conceptual issues in, 21–23
368 delirium and, 262
Acetaminophen, 327, 328, 338 diversity in patterns of, 12–15
Acetazolamide, 78 elder abuse and, 372
Acetylcholinesterase, 207 general trends in, 25–28
Acquired immunodeficiency syndrome increase in older adults as
(AIDS), and dementia, 249 percentage of population, 1–2
Activated or hyperactive subtype, of influence on mental disorders of
delirium, 258 early onset, 339–341
Activities of daily life Mini-Mental State Examination
Alzheimer’s disease and, 202 and, 180
cognitive changes of normal aging personality and emotional changes
and, 32–34 in, 38–43
rating scales and, 183–184, 384– prevalence of Alzheimer’s disease by,
385 193
Acute treatment, for bipolar disorder, processing resource model of
163–165 cognitive abilities and,
Adjustment 23–38
anxiety and, 276–277 psychosis and, 294
bereavement and, 69 sexual dysfunction and, 329–331
Advance directives, and competency, sleep and advancing, 313
349–352 social context of, 43–48
African Americans. See Black Age-associated memory impairment
Americans (AAMI), 35–36, 37
389
Age of onset. See also Age and aging; Alprazolam

Early onset; Late onset anxiety disorders and, 291, 292
Alzheimer’s disease and, 192 insomnia and, 317, 318
anxiety disorders and, 278 Alprostadil, 334
bipolar disorder and, 113 Alternative approaches, to treatment of
dysthymic disorder and, 91, 92 depression, 161–162
frontotemporal dementia and, Alzheimer’s Association, 213
231 Alzheimer’s disease
major depression and, 83 clinical presentation of, 197, 199
psychopharmacotherapy for Cognistat profile and, 383
depression and, 147 competency to drive and, 368, 370
Agitated Behavior in Dementia scale, dementia and, 88, 239–240, 250
217–218 depression and, 73–74, 90
Agitation diagnosis of, 195–205, 198–199
psychopharmacotherapy for differential diagnosis of, 205–206,
Alzheimer’s disease and, 214, 250
216–218, 220 epidemiology of, 7, 192–195
vascular dementia and, 246 frontotemporal dementia and, 232,
AIDS dementia complex, 249 234, 236
Alcohol and alcohol abuse. See also genetics of, 208
Substance abuse Mini-Mental State Examination
assessment of, 323–325 and, 178–179
associated psychiatric conditions neurobiochemistry of, 207–208
and, 321–323 neuropathology of, 206–207
delirium and withdrawal from, psychopharmacotherapy for, 213–
263 220
diagnosis of, 321 psychosocial theory of, 208–210
epidemiology of, 320–321 psychotherapy for caregivers, 210–
risk factors for, 321 213
substance-induced dementia and, Alzheimer’s Disease Assessment Scale,
254–255 213, 241
symptoms of depression induced by, American Academy of Neurology,
78 368
treatment of, 325–326 American Medical Association, 350,
Alcohol Use Disorders Identification 372
Test (AUDIT), 323–324 Amitriptyline, 134
Index 391
Amnestic disorders, and Alzheimer’s Alzheimer’s disease and, 219

disease, 205 anxiety disorders and, 292
Amnestic mild cognitive impairment, anxiety symptoms induced by, 277
36 automobile driving and, 370–371
Amoxapine, 138 cytochrome P450 system and, 140–
Amphetamines, and depression, 137, 141
153 dosages of, 148
Amyloid precursor protein (APP), and management of side effects of, 148–
Alzheimer’s disease, 206 149
Analgesics. See also Narcotic analgesics; predictors of response to, 147
Nonsteroidal anti-inflammatory receptor affinities of, 134–135
agents sexual dysfunctions and, 332
substance abuse and, 327, 328 treatment resistance and, 153–155
symptoms of depression induced by, Antiepileptic agents, and depression, 78
78 Antihistamines
Animal models, for pathogenesis of Alzheimer’s disease and, 219
anxiety disorders, 287 drug-drug interactions and, 139
Animal Naming task, 174, 175, 181– medication-induced mental
182 disorders and, 56
Anorexia, and depression, 90 substance abuse and, 327, 328
Anterior cingulate syndrome, 335 Antihypertensive agents
Anticholinergic agents sexual dysfunction and, 332
anxiety symptoms and, 277 symptoms of depression induced by,
delirium and, 263–264 78
Anticholinergic effects, of tricyclic Antioxidants, and Alzheimer’s disease,
antidepressants, 149 194
Anticipatory anxiety, and panic attacks, Antiparkinsonian agents
281 medication-induced mental
Anticonvulsants disorders and, 56
Alzheimer’s disease and, 218 psychosis and, 303
cytochrome P450 system and, 140 Antipsychotics. See also Atypical
Antidepressants. See also Selective antipsychotics
serotonin reuptake inhibitors; anxiety disorders and, 292
Tricyclic antidepressants bipolar disorder and, 163
advantages and disadvantages of, cytochrome P450 system and, 140
136–137 delirium and, 264
Antipsychotics (continued) Arteriosclerosis, and vascular dementia,

dementia with Lewy bodies and, 191, 246
241 Asparaginase, 79
late-onset psychosis and, 303–306 Aspirin, 328
psychotic depression and, 156 Assessment. See also Diagnosis
sexual dysfunctions and, 332 of alcohol abuse or dependency,
symptoms of depression induced by, 323–325
78 of competency, 356–358
vascular dementia and, 248 elder abuse and, 373
Anxiety of erectile dysfunction, 335
Alzheimer’s disease and, 218 of insomnia, 313, 314
mood disorder with, 283, 285 of suicidality in elderly, 105–106,
schizophrenia with, 285–286 107
Anxiety disorders Attorney-in-fact, 350, 351
autonomic and psychomotor Atypical antipsychotics. See also
features of, 275 Antipsychotics
clinical presentation of, 274 Alzheimer’s disease and, 216–217
diagnosis of, 276–286 dementia with Lewy bodies and,
epidemiology of, 273–274 241
laboratory evaluation of, 276 psychosis and, 302–303, 304
pathogenesis of, 286–288 AUDIT-5 (five-item Alcohol Use
rating scales for, 274–276 Disorders Identification Test),
treatment of, 288–293 323–324
Anxiolytic agents Auditory acuity, and normal aging, 24
Alzheimer’s disease and, 218 Augmentation, of antidepressants, 154–
symptoms of depression and, 78 155
Apathy, and Alzheimer’s disease, Automobiles. See Driving
219
APOE4, and Alzheimer’s disease, 192– Baclofen, 79
193, 205 Barbiturates
Appetite, and major depression, 83 delirium and withdrawal from, 263
Aripiprazole substance abuse and, 328
Alzheimer’s disease and, 216, 220 symptoms of depression induced by,
dementia with Lewy bodies and, 79
241 Beck Anxiety Inventory, 275–276
psychosis and, 304 Beck Cognitive Insight Scale, 301
Index 393
Beck Depression Inventory (BDI), 100, Bereavement

101, 103 depression compared to “normal,”
Beck Depression Inventory for Primary 68–70
Care (BDI-PC), 102, 105 loss and, 80, 108
Beck Hopelessness Scale, 106 widowhood and, 46–47
Behavior. See also Agitation; Behavior Bibliotherapies, for depression, 161–
therapy 162
complications of vascular dementia Biology, of aging, 48–61. See also
and, 248 Genetics; Neurobiological theories
interventions for insomnia, 315– Bipolar disorder. See also Hypomania;
316 Mania
major depression and regression of, aging and early-onset, 339
90–91 clinical presentation of, 113
Behaviorally oriented pain management epidemiology of, 111, 113
training, 338 pathogenesis and theories of, 115–
Behavior Pathology in Alzheimer’s 116
Disease Rating Scale (BEHAVE- psychopharmacotherapy for, 157,
AD), 217–218 163–166
Behavior therapy. See also Cognitive- treatment of, 162–163
behavioral therapy Black Americans
Alzheimer’s disease and, 216 caregivers for dementia patients and,
anxiety disorders and, 288–290 211, 212
geriatric depression and, 128 patterns of health and aging in, 12–
late-onset psychosis and, 300–302 14
Benzodiazepines poverty rates and, 45
Alzheimer’s disease and, 216, 219 Blessed Information Memory
anxiety disorders and, 290–292, Concentration Test, 183
291 β-Blockers
competency to drive and, 370 medication-induced mental
delirium and withdrawal from, 263 disorders and, 56
insomnia and, 317–319 substance-induced mood disorder
psychosis and, 303 and, 77
substance abuse and, 326, 327, symptoms of depression induced by,
328 78
symptoms of depression induced by, Boston Naming Test (BNT), 188,
78 357
Braak’s criteria, for Alzheimer’s disease, Caregivers

195, 196 psychotherapy for dementia and,
Brief dynamic therapy, for geriatric 210–213
depression, 130 relief after death of patient, 69–70
Bronchodilators resources for, 228
anxiety symptoms induced by, 277 social context of aging and, 48
medication-induced mental Case examples
disorders and, 56 of biology of aging, 51
Bupropion of insomnia, 318–319
advantages and disadvantages of, of major depression, 85–86
136 of psychotic depression, 84
depression and, 138, 143–144, 148 Category fluency measures, 181–182
receptor affinities of, 134 Center for Epidemiologic Studies
Buspirone, 292 Depression Scale, 69–70, 90, 93
Cerebrovascular disease. See also Stroke
Caffeine dementia with Lewy bodies and,
anxiety and, 277 237
substance abuse and, 327, 328 vascular dementia and, 242, 245
CAGE Questionnaire, 323–325 Chemotherapeutic agents, and
Calcium channel blockers, and symptoms of depression, 78–79
symptoms of depression, 78 China, older adults as percentage of
California, and laws on competency, population of, 2
348, 349, 351, 354, 361, 362, Chloral hydrate, 318, 328
363–365 Chlordiazepoxide, 291
California Verbal Learning Test Chlorpheniramine, 328
(CVLT), 187 Chlorpromazine, 304
Cannabis, 326–327 Choline acetyltransferase, and
Capacity. See also Competency Alzheimer’s disease, 207
contracts and, 351 Cholinesterase inhibitors
testamentary, 354–356 Alzheimer’s disease and, 213, 214,
Carbamazepine, and bipolar disorder, 215, 218
164–165, 166 delirium and, 263, 264
Cardiovascular system, and biological dementia due to general medical
aging, 52. See also Heart disease; conditions and, 253
Stroke; Vascular disorders; dementia with Lewy bodies and,
Vascular lesions 240–241
Index 395
substance-induced persisting Clonazepam

dementia and, 254 pharmacological properties of, 291
vascular dementia and, 247 psychosis and, 303
Chronic illness, and major depression, Clonidine, 78
71–72. See also Medical conditions Clorazepate, pharmacological
Chronic pain, 337–339 properties of, 291
Cimetidine, 79 Clozapine, and late-onset psychosis,
Citalopram 303, 304
anxiety disorders and, 292 Cocaine, 326
depression and, 139, 143, 148 Code of Federal Regulations, 352
receptor affinities of, 134 Codeine
Clinical Dementia Rating (CDR), 368 substance abuse and, 328
Clinical Global Impression (CGI), 160 symptoms of depression induced by,
Clinical implications. See also 78
Treatment Cognistat, 175, 383
of biology of aging, 50–61 Cognitive Abilities Screening
of cognitive change in aging, 34–35 Instrument (CASI), 174, 175,
of personality and emotional 181
changes in aging, 42–43 Cognitive and behavioral theories, of
Clinical interview, and assessment of depression, 108–109
competency, 356–357 Cognitive-behavioral therapy. See also
Clinical presentation Behavior therapy
of age-associated memory for anxiety disorders, 288–289
impairment, 37 for geriatric depression, 128–129
of Alzheimer’s disease, 197, 199 for insomnia, 316
of anxiety disorders, 274 for late-onset psychosis, 300–302
of bipolar disorder, 113 Cognitive impairment. See also
of delirium, 257 Executive functions; Learning;
of dementia with Lewy bodies, Memory
238 aging effects on performance and,
of frontotemporal dementia, 26–27
231 alcohol abuse or dependency and,
of psychosis, 294, 296 321–323
of social context of aging, 48 competency assessment and, 357–
of vascular dementia, 243 358
Clock Drawing Test, 176, 182, 368 delirium and, 262
Cognitive impairment (continued) caring for oneself and management

depression and, 83, 87–91, 128, of finances, 360–362
147 contracts and gifts, 353–354
evaluation of Alzheimer’s disease definition of, 347–348
and, 200–201, 202 driving and, 367–371
late-onset psychosis and, 297 enrollment in research studies and,
processing resource model of, 23–38 352, 353
psychopharmacotherapy for informed consent for medical care
Alzheimer’s disease and, 213– and, 348–349, 349
220 surrogate decision-makers and,
risk of in older adults, 7 363–365
standardized measures for rating, trusts and, 356
174–183 wills and, 354–356
variables of in normal aging, 29 Compliance, with treatment for
vascular dementia and, 243, 247– depression, 131–132
248 Complicated grief, 70, 71
Cohen-Mansfield Agitation Inventory, Computed tomography, in diagnosis
217–218 of Alzheimer’s disease, 198, 201, 250
Cohort effects, on cognition in normal of delirium, 261
aging, 29 of dementias, 185, 250–252
Combined treatment, for geriatric dementia with Lewy bodies, 237
depression, 132, 155 frontotemporal dementia, 234
Community-based programs, for vascular dementia, 245
substance abuse, 329 of depression, 97
Comorbidity, of psychiatric disorders of hypomania or mania, 116
alcohol abuse or dependency and, Computers. See Web sites
321–323 Confusion Assessment Method (CAM)
diagnosis and treatment of algorithm, 258–259, 260
depression and, 129 Congestive heart failure, 72
personality disorders and, 340 Conservators and conservatorship,
Competence Assessment Tool for 361–362, 363–365
Psychiatric Advance Directives, Consortium to Establish a Registry for
358 Alzheimer’s Disease (CERAD)
Competency Word List Learning, 188, 195,
advance directives and, 349–352 196–197, 203
assessment of, 356–358 Continuity, in personality, 39
Index 397
Contracts, and competency, 351, 353– Delirium

354, 359 Alzheimer’s disease and, 206
Contraindications, for tricyclic diagnostic criteria for, 258
antidepressants, 138 differential diagnosis of, 259, 261–
Control, and emotional changes during 262
aging, 41, 42 epidemiology of, 256–257
Controlled Oral Word Association Test laboratory evaluation of, 259–260,
(COWAT), 188 261
Coping, and emotional changes during mental status examination and,
aging, 40–42 257–259
Cornell Scale for Depression in pathogenesis of, 262
Dementia, 101, 104–105 patient history and clinical
Costs, of health care for older adults, 5– presentation of, 257
6 prognosis in, 264
Counseling, and alcohol abuse and psychosis and, 298, 337
dependency, 325 treatment of, 263–264
Creutzfeldt-Jakob disease, and vascular dementia and, 246
dementia, 252 Delirium Rating Scale, 258, 259
Cross-sectional view, of aging, 22 Delis-Kaplan Executive Function
Culture System, 234
access to mental health services and, Delusions and delusional disorder
14 Alzheimer’s disease and, 197, 199
caregivers for dementia patients and, diagnostic criteria for, 296
213 late-onset psychosis and, 299, 306
Cytochrome P450 system, and psychotic depression and, 84
psychotropic medications, 138, psychotic disorder due to a general
139, 140–141, 142, 143, 144 medical condition and, 336
Dementia. See also Dementia due to
Death, leading causes of in older adults, general medical conditions;
3. See also Mortality Dementia with Lewy bodies;
Decisional competency, 347–348 Frontotemporal dementia; Mixed
Decongestants dementia; Reversible dementia;
anxiety symptoms induced by, 277 Substance-induced persisting
medication-induced mental dementia; Vascular dementia
disorders and, 56 alcohol-related, 322, 324
substance abuse and, 327 Alzheimer’s disease and, 205
Dementia (continued) importance of in older adults, 7–8,

chronic pain and, 338–339 67
competency to drive and, 368, 369– laboratory evaluation of, 95–96, 97
370, 371 medical conditions and, 70–76
delirium and, 259, 261–262 minor or subthreshold forms of, 92–
diagnosis of, 173–186, 187–189 93, 94–95
differentiation of common forms, normal grief and, 68–70
250–252 personality disorders and, 340
etiologies of, 186, 190–191 problems in diagnosis and treatment
major depression and, 89 of, 129
mild cognitive impairment and psychological tests for, 96–97
progression to, 36–38 psychopharmacotherapy for, 132–
psychosis and, 337 156, 218–219
psychotherapy for caregivers, 210– psychotherapy for, 127–130
213 rating scales and, 97–105
resources for caregivers, 228 theories of, 107–110
Dementia due to general medical undertreatment of, 67–68
conditions, 249–254 Depressive personality disorder, 95
Dementia with Lewy bodies, 235, 237– Depressive pseudodementia, 87
241 Desipramine, and depression, 134, 146
Dementia Rating Scale (DRS), 174, Detoxification, and substance abuse,
176, 178 329
Dementia syndrome of depression Developmental optimism, 38
(DSD), 87–88 Dexamethasone, and depression, 79,
Depression. See also Major depression 96
aging and early-onset, 339 Diagnosis. See also Assessment;
alcohol abuse or dependency and, Differential diagnosis; DSM-IV-
323 TR; Rating scales;
Alzheimer’s disease and, 218–219 Underrecognition
chronic pain and, 338 of age-related cognitive change and
complementary and alternative mild cognitive impairment,
approaches to treatment of, 35–38
161–162 of alcohol abuse or dependency, 321
dementia and, 89 of Alzheimer’s disease, 195–197,
experimental therapies for, 198–199
159–160 of anxiety disorders, 276–286
Index 399
biological aging and guidelines for, psychosis and, 298, 337

55 vascular dementia and, 245–246
of delirium, 258 Differential vulnerability hypothesis,
of dementia with Lewy bodies, 237– for posttraumatic stress disorder,
238 281–283
of dementia with unspecified cause, Digoxin, 79
173–186 Diphenhydramine
of depression due to a general Alzheimer’s disease and, 219
medical condition, 70–76 substance abuse and, 328
of depressive personality disorder, Direct Assessment of Functioning
95 Scale, 184
of dysthymic disorder, 91–92 Disability, rates of in older adults, 3–4
of frontotemporal dementia, 229, Disulfiram, 79
230–231 Divalproex, and bipolar disorder, 164,
of hypomania and mania, 110–117 165, 166
of major depression, 80–91, 129 Diversity, in patterns of health and
of minor depression, 92–95 aging, 12–15
of mixed mood disorder, 117 Doctor-patient relationship, and age-
of substance-induced mood related cognitive changes, 34
disorder, 76–80 Donepezil
of vascular dementia, 241–242, 243 Alzheimer’s disease and, 213, 215,
Diazepam 218
insomnia and, 318 delirium and, 263, 264
pharmacological properties of, dementia with Lewy bodies and,
291 240–241
Differential diagnosis. See also vascular dementia and, 247
Diagnosis Dosage. See also
Alzheimer’s disease and, 205–206 Psychopharmacotherapy
delirium and, 259, 261–262 of antidepressants for geriatric
dementia with Lewy bodies and, depression, 148
240 of antipsychotics
frontotemporal dementia and, 234, for Alzheimer’s disease, 217
236 for bipolar disorder, 163
insomnia and, 313–315 for late-onset psychosis, 303–
normal grief and bereavement, 68– 306
70 of carbamazepine, 164
Dosage (continued) major depression and, 82, 85

of lamotrigine, 165 mania and hypomania in, 114–115,
of monoamine oxidase inhibitors, 117
152 minor depressive disorder and, 94–95
Double depression, 91 obsessive-compulsive disorder and,
Doxepin, 134 282
Driving panic disorder and, 281, 283
cognitive changes of aging and, 33 personality change due to a general
competency to, 367–371 medical condition and, 336
Drop-out rates, from treatment for phobias and, 280
depression, 131–132 posttraumatic stress disorder and,
Drug-drug interactions 284–285
monoamine oxidase inhibitors and, psychiatric illness related to a
139, 152–153, 155 general medical condition and,
selective serotonin reuptake 334
inhibitors and, 139, 155 psychosis and, 293
DSM-III-R, and late-onset psychosis, schizophrenia and, 286, 295
293 substance abuse and, 322, 323
DSM-IV-TR. See also Diagnosis substance-induced mood disorder
age-related cognitive changes and, and, 76
35, 36 vascular dementia and, 242, 243
alcohol abuse or dependency and, Duloxetine
321, 322 advantages and disadvantages of,
Alzheimer’s disease and, 195, 196, 136, 145
203 chronic pain and, 338
anxiety disorders and, 274, 279 receptor affinities of, 134
delirium and, 257, 258 Durable power of attorney for health
delusional disorder and, 296 care (DPAHC), 363
dementia due to general medical Dysthymic disorder, 91–92
conditions and, 249
depression due to a medical Early onset. See also Age of onset
condition and, 68 influence of aging on disorders of,
depressive personality disorder and, 339–341
95 of major depression, 83
dysthymic disorder and, 91 Economics. See Costs; Financial
insomnia and, 316 decision making; Financial status
Index 401
Education. See also Learning Ephedrine, 328

cognition in normal aging and, Epidemiologic Catchment Area (ECA)
29 Study, 6, 92, 111, 273
Mini-Mental State Examination Epidemiology
and, 180 of alcohol abuse and dependency,
social context of aging and, 43–45, 320–321
44 of Alzheimer’s disease, 192–195
treatment of depression and, 161– of anxiety disorders, 273–274
162 of bipolar disorder, 111, 113
Elder abuse, 371–373 of delirium, 256–257
Electrocardiogram of dementia with Lewy bodies, 237
in laboratory evaluation of frontotemporal dementia, 229
of delirium, 261 of major depression, 80
of dementia, 185 of substance abuse, 326–327
lithium and, 165, 166 of vascular dementia, 241
tricyclic antidepressants and, 145 Erectile dysfunction (ED), 330, 331–
Electroconvulsive therapy (ECT) 332, 333, 334, 335
major depression and, 157–159 Escitalopram, and depression, 139,
manic episodes following, 111, 114, 148
117 Estrogen, and Alzheimer’s disease, 194
psychotic depression and, 156 Eszopiclone, and insomnia, 318, 319,
Electroencephalogram 320
diagnosis of Etiology, of dementia, 186, 190–191.
Alzheimer’s disease, 198, 201 See also Pathogenesis and
Creutzfeldt-Jakob disease, 252 pathology
delirium, 261 Executive functions. See also Cognitive
dementia with Lewy bodies, 237 impairment
frontotemporal dementia, 230 aging effects on cognitive
in laboratory evaluation of performance and, 27, 32
dementia, 185 competency assessment and, 358
Emotions, and changes in normal Executive Interview, 232
aging, 40–42 Exercise, and treatment of depression,
Endocrine disorders, and dementia, 161
190 Experimental therapies, for depression,
Endocrine system, and biological aging, 159–160
53 Explicit memory, 30
Family. See also Caregivers Frontal lobe hypothesis, and

grandparents and, 48 neuropsychological model of
legal issue of undue influence and, normal aging, 25
360 Frontal Systems Behavior Scale, 232
marriage and, 45–47 Frontotemporal dementia, 229–235,
social context of aging and, 47–48 236
substance abuse and, 329 Functional competency, 348
Family history, of frontotemporal Functional magnetic resonance imaging
dementia, 231. See also Genetics (fMRI), and Alzheimer’s disease,
Family therapy 203, 204
dementia caregivers and, 211–212
geriatric depression and, 130 Galantamine
late-onset psychosis and, 302 Alzheimer’s disease and, 213, 215
Fatality rate, for older drivers, 367. See vascular dementia and, 247
also Mortality Gastrointestinal system, and biological
Fatigue, and depression, 83 aging, 52
Feeling Good (Burns 1999), 162 Gender, and cognition in normal aging,
Filter hypothesis, for schizophrenia, 14, 29. See also Women
300 Generalized anxiety disorder
Financial decision making, and legal autonomic and psychomotor
surrogates, 365 features of, 275
Financial status, and social context of diagnosis of, 277–278, 279
aging, 43–45 prevalence of, 273
Fluoxetine treatment of, 289, 290, 292
depression and, 139, 142 Genetics. See also Family history
receptor affinities of, 134 Alzheimer’s disease and, 192–193,
Fluphenazine, and psychosis, 303, 304 208
Flurazepam, 318 biological aging and, 49–50
Fluvoxamine, and depression, 139, 142 cognition in normal aging and, 29
Food and Drug Administration (FDA), personality and, 39
216–217, 248, 352 pharmacogenetics and, 58
Freud, Sigmund, 108 Genitourinary system, and biological
Friendship, and social context of aging, aging, 53
47–48 Geriatric Depression Scale (GDS), 75,
Frontal Assessment Battery (FAB), 232 100, 101, 103, 380–381
Frontal Behavioral Inventory, 232–233 Geriatric Mental State Schedule, 75
Index 403
Gifts, and competency, 353–354 Hasegawa Dementia Scale, 181

Gingko biloba, and Alzheimer’s disease, Hayflick phenomenon, 49
214 Head injury
Global Study of Sexual Attitudes and dementia and, 251, 253
Behaviors, 330, 331 secondary mania and, 112
Glutethimide, 318 Health, personality and perceptions of,
Grandparents, and caregiving, 48 40. See also Health care; Medical
Grief. See Bereavement; Complicated conditions; Public health
grief Health care. See also Hospitalization;
Group therapy Insurance; Medical evaluation;
geriatric depression and, 130, 161 Medicare; Nursing homes;
late-onset psychosis and, 302 Primary care physicians
Guanethidine, and depression, 78 informed consent and, 348–349,
Guardians and guardianship, 361–362, 349
363 overview of for older adults, 3–6
Guidelines Health and Retirement Study, 7
for diagnostic process with older Heart disease, and depression, 72–73
adults, 55 Heavy metals, and dementia,
for treatment of older adults, 55–61 191
Heterogeneity, in patterns of aging, 22–
Hallucinations 23
late-onset psychosis and, 296 Highly active antiretroviral therapy
psychotic depression and, 84 (HAART), 249
psychotic disorder due to a general Hispanic Americans
medical condition and, 336 caregivers for dementia patients and,
Haloperidol 211, 212–213
Alzheimer’s disease and, 217, 220 Mini-Mental State Examination
bipolar disorder and, 163 and, 181
delirium and, 264 patterns of health and aging in, 12–
psychosis and, 303, 304 14
symptoms of depression induced by, poverty rates and, 45
78 HIV dementia, 249, 250
Hamilton Anxiety Rating Scale, 274– Home visits, and geriatric depression,
275 128
Hamilton Rating Scale for Depression Hormone replacement therapy, and
(Ham-D), 81, 101, 104, 132, 160 Alzheimer’s disease, 194
Hospitalization Informant Questionnaire on Cognitive

anorexia and depression, 90 Decline in the Elderly
rates of for older adults, 3 (IQCODE), 184
Huntington’s disease, and dementia, Informed consent, for medical care,
251, 253 348–349, 349
Hypertension Inoculation hypothesis, for
caution with lithium and, posttraumatic stress disorder, 281–
165–166 283
and side effects of Insight-oriented psychotherapy, for
monoamine oxidase inhibitors, late-onset psychosis, 302
152 Insomnia. See also Sleep disturbance
tricyclic antidepressants, 149 Alzheimer’s disease and, 219
Hypnotic agents. See also assessment of, 313, 314
Benzodiazepines; Sedative- diagnostic criteria for, 316
hypnotics differential diagnosis of, 313–315
Alzheimer’s disease and, 219 sleep hygiene and, 316, 317
insomnia and, 319–320 treatment of, 315–320
Hypochondriasis, and major Institutional Review Board (IRB), 352
depression, 86 Instruction directives, 350
Hypomania. See also Bipolar disorder Instrumental Activities of Daily Living
diagnosis of, 110–117 (IADL) Scale, 184, 384–385
psychosis and, 298 Insurance, and barriers to geriatric
treatment of, 162 mental health care, 11–12. See also
Medicare
Imipramine, 134 Intelligence, and aging effects on
Immunological system, and biological cognitive performance, 26
aging, 54 International Classification of Sleep
IMPACT (Improving Mood- Disorders, The (American Sleep
Promoting Access to Collaborative Disorders Association 1997), 316
Treatment) project, 105, 131 International Late-Onset Schizophrenia
Implicit memory, 30 Group, 294
Implied consent, 349 Internet. See Web sites
Incidental recall, 30 Interpersonal psychotherapy, for
Infectious diseases geriatric depression, 129–130
dementia and, 190 Intracavernosal self-injection, 333–334
secondary mania and, 112 Isotretinoin, 79
Index 405
Japan, and Hasegawa Dementia Scale, Learned helplessness, and depression,

181 108–109
Learning. See also Cognitive
Keep Your Brain Young (McKhann and impairment; Education
Albert 2002), 31 cognition in normal aging and, 30–
Knowledge, needed for effective work 31, 33–34
with elderly patients, 15 psychotherapy for depression and,
Korsakoff ’s syndrome, 205, 254, 128
255 Learning Throughout Life (National
Korsakoff-type anemia, 321–322 Retired Teachers Association et al.
Kraepelin, Emil, 115 2004), 31
Legal issues
Laboratory evaluation. See also Medical caring for oneself and management
evaluation of finances, 360–362
of Alzheimer’s disease, 203 competency and, 347–358
of anxiety disorders, 276 driving and, 367–371
of delirium, 259–260, 261 elder abuse and, 371–373
of dementia of unspecified type, surrogate decision-makers and,
185 360–362, 363–365
of depression, 95–96, 97, 147 undue influence and, 358–360
of frontotemporal dementia, 234 Levodopa, 79
of hypomania and mania, 116 Levonorgestrel implant, 79
of vascular dementia, 245 Lewis, Sir Aubrey, 110
Lamotrigine Lewy bodies, 240
bipolar depression and, 157 dementia with, 235, 237–241
bipolar disorder and, 164, 165 Life expectancy, 1–2, 12
Language Lifestyle modifications, for treatment of
aging effects on cognitive depression, 161
performance and, 26 List-learning tasks, and Alzheimer’s
evaluation of Alzheimer’s disease disease, 203
and, 202 Lithium
Mini-Mental State Examination advantages and disadvantages of,
and, 179, 181 137
Late onset. See also Age of onset Alzheimer’s disease and, 216, 219
of major depression, 83 augmentation of antidepressants,
of psychosis, 293–306 154–155
Lithium (continued) Major depressive disorder, in partial

bipolar depression and, 157 remission, 92
bipolar disorder and, 163–166 Management, of chronic pain, 338
Liver damage, and acetaminophen, Mania. See also Bipolar disorder
327 diagnosis of, 110–117
Living will, 350, 363 psychosis and, 298
Longitudinal Aging Study Amsterdam, treatment of, 162
72 MAOIs. See Monoamine oxidase
Longitudinal view, of aging, 22 inhibitors
Long-term management, of bipolar Maprotiline, 138
disorder, 165 Marriage, and social context of aging,
Long-term memory, 30 45–47
Lorazepam Masked depression, 85–87
Alzheimer’s disease and, 217 Massachusetts Male Aging Study,
anxiety disorders and, 290, 291 330
delirium and, 263, 264 MCMI-III (Millon Clinical Multiaxial
insomnia and, 318 Inventory–III), 98
psychosis and, 303 Medical conditions. See also Health;
Loss, and depression, 80, 108. See also Health care; Neurological
Bereavement disorders
anxiety and, 277
MacArthur Competence Assessment delirium and, 257, 258
Tool—Treatment, 358 dementia and, 190–191, 249–254
Magnetic resonance imaging (MRI) depression due to, 70–76
and Alzheimer’s disease, 203, 204 diagnosis and treatment of
and other dementias, 252 depression and, 129
dementia with Lewy bodies, 237 insomnia and, 315
frontotemporal dementia, 234 mania due to, 111, 112–113
vascular dementia, 245 psychiatric illness due to, 334–337
Maintenance treatment, with psychotherapy for depression and,
antidepressants, 156 128
Major depression. See also Depression psychotic disorder due to, 336–337
chronic illness and, 71–72 sexual dysfunction and, 331–332
diagnosis of, 80–91 Medical evaluation. See also Laboratory
electroconvulsive therapy for, 157– evaluation; Neurological
159 examination
Index 407
dementia with Lewy bodies and, Memory. See also Cognitive

239 impairment; Working memory
frontotemporal dementia and, 230– aging effects on cognitive
231, 233 performance and, 26–27, 28,
lithium therapy for bipolar disorder 30–32
and, 165–166 Alzheimer’s disease and, 202
vascular dementia and, 243–244 clinical presentation of loss in old
Medicare, 5, 11, 329 age, 37
Medications. See also Anticonvulsants; electroconvulsive therapy and,
Antiepileptic agents; Antihista- 159
mines; Antihypertensive agents; psychotherapy for depression and,
Antiparkinsonian agents; Over- 128
dose; Psychopharmacotherapy; Memory and Behavior Problems
Steroids; Treatment; Withdrawal Checklist, 212
anxiety symptoms produced by, 277 Memory Impairment Screen (MIS),
cognitive changes of aging and 177, 183
monitoring of, 33 Memory Prescription, The (Small 2004),
competency to drive and, 370–371 31
dementia induced by, 191 Memory training, for Alzheimer’s
depression symptoms induced by, disease, 209
78–79 Mental activity, and cognition in
diagnosis and treatment of normal aging, 29
depression and, 129 Mental disorders. See also Age of onset;
guidelines for older adults and, 55– Comorbidity; Diagnosis;
61 Psychiatric illness related to a
insomnia and, 315 general medical condition;
prescription of potentially addictive Treatment
substances and, 330 influence of aging on disorders of
sexual dysfunction and, 332 early onset, 339–341
signs and symptoms of mental medication-induced signs and
disorder induced by, 56 symptoms of, 56
Mefloquine, 79 overview of in older adults, 6–8, 9
Memantine prevalence of for minority groups,
Alzheimer’s disease and, 208, 213– 13–14
214, 215 underrecognition of in older adults,
vascular dementia and, 247 10
Mental health care, barriers to geriatric, Mild decline, 25

8–12 Millon Clinical Multiaxial Inventory–
Mental health professionals. See also III (MCMI-III), 98
Psychiatrists Mini-Cog, 174, 177, 182
barriers to geriatric mental health Mini-Mental State Examination
care and, 11 (MMSE)
working effectively with older cognitive impairment and, 174,
adults, 15–16 175, 178–181, 357
Mentally disabled persons, and depression and, 74, 88
competency, 352 frontotemporal dementia and,
Mental status examination. See also 232
Mini-Mental State Examination sample items from, 179
(MMSE) schizophrenia and, 339
Alzheimer’s disease and, 202 Minnesota Multiphasic Personality
caution in interpretation of, 34 Inventory–2 (MMPI-2), 98
delirium and, 257–259 Minor depression, 92–95
dementia of unspecified cause and, Mirtazapine
173–174, 175–177 advantages and disadvantages of,
vascular dementia and, 243 136
Meperidine, and depression, 78, 152 depression and, 138, 144
Metabolic disturbances, and mania, receptor affinities of, 134
112 Mixed dementia, 248–249
Methyldopa, 78 Mixed episode, of hypomania and
Methylphenidate mania, 117
advantages and disadvantages of, Mixed mood disorder, 117
137 MMSE. See Mini-Mental State
Alzheimer’s disease and, 219 Examination
depression and, 153 MMPI-2 (Minnesota Multiphasic
Methylsergide, 79 Personality Inventory–2), 98
Methyprylon, 318 Mnemonic training, 31
Metoclopramide, 79 Moclobemide
Metronidazole, 79 depression and, 150, 151, 152, 155
Meyer, Adolf, 110 frontotemporal dementia and, 235
Michigan Alcoholism Screening Test— Modafinil
Geriatric Version, 323–324 Alzheimer’s disease and, 219
Mild cognitive impairment, 35–38 depression and, 153
Index 409
Moderate decline, 25 Naltrexone, 325

Modified Ischemic Score, and vascular Narcotic analgesics
dementia, 244 medication-induced mental
Molindone, 78 disorders and, 56
Monoamine oxidase inhibitors substance abuse and, 328
(MAOIs) symptoms of depression induced by,
advantages and disadvantages of, 78
137 National Bioethics Advisory
bipolar depression and, 157 Commission, 352
depression and, 149–153, National Center on Elder Abuse,
154 373
drug-drug interactions and, 139, National Elder Abuse Incidence Study,
152–153, 155 371–372
sexual dysfunction and, 332 National Household Survey on Drug
Mood disorders. See also Bipolar Abuse, 326
disorder; Depression; Mixed National Institute on Aging and Ronald
mood disorder and Nancy Reagan Institute of the
influence of aging on early-onset, Alzheimer’s Association criteria,
339 for Alzheimer’s disease, 196
mood disorder with anxiety and, National Institute of Neurological and
283, 285 Communicative Disorders and
treatment of vascular dementia and, Stroke (NINCDS), 195, 198–
248 199, 203
Mood stabilizers. See also Lithium National Institutes of Health, 109
Alzheimer’s disease and, 219 Neglect, and elder abuse, 372
bipolar disorder and, 166 NEO Five-Factor Inventory (NEO-
Morale, and emotional changes in FFI), 98
aging, 41 Neoplasms, and mania, 112
Mortality. See also Death; Fatality rate Nervous system, and biological aging,
delirium and rates of 53
posthospitalization, 263 Neurobehavioral Cognitive Status
poststroke depression and, 73 Examination (NCSE), 174,
Musculoskeletal system, and biological 175
aging, 54 Neurobiochemistry, of Alzheimer’s
Myocardial infarction, and depression, disease, 207–208. See also
72 Neurotransmitters
Neurobiological theories. See also Neuropsychology, and cognitive

Neuropsychology; changes in aging, 24–25. See also
Neurotransmitters Neurobiological theories;
of anxiety disorders, 286–288 Neuropsychological tests;
of bipolar disorder, 116 Neurotransmitters
of depression, 109–110 Neuroticism, and depression, 110
of psychosis, 299–300 Neurotransmitters. See also
Neurofibrillary tangles, and Alzheimer’s Neurobiochemistry;
disease, 206 Neurobiological theories
Neuroleptics. See Antipsychotics; anxiety disorders and, 286–288
Atypical antipsychotics bipolar disorder and, 116
Neurological disorders. See also depression and, 109–110
Neuropathology New Jersey, and In re Conroy case, 351–
dementia and, 190 352
secondary mania and, 113 Nocturnal myoclonus, 315
Neurological examination Nonamnestic mild cognitive
for dementia with Lewy bodies, impairment, 36
239 Nonarteritic anterior ischemic optic
for vascular dementia, 243–244 neuropathy (NAION), 333
Neuropathology, of Alzheimer’s disease, Nonbenzodiazepine hypnotics, 319–
195–197, 206–207 320
Neuropsychiatric Inventory (NPI), 74, Nonresponse, to antidepressants,
184–185, 212, 233, 388 154
Neuropsychological Assessment Battery, Nonsteroidal anti-inflammatory agents
368–369 (NSAIDs). See also Analgesics
Neuropsychological tests. See also Alzheimer’s disease and, 193–194,
Neuropsychology; Rating scales 214
for Alzheimer’s disease, 202–203 caution with lithium and, 165–166
for dementia with Lewy bodies, chronic pain and, 338
239–240 competency to drive and, 371
for dementia of unspecified cause, substance abuse and, 328
186, 187–189 symptoms of depression induced by,
for frontotemporal dementia, 233– 78
234, 236 Noradrenergic system, and anxiety
for psychosis, 296–297 disorders, 286–287
for vascular dementia, 244–245 Normative fallacy, 67
Index 411
Nortriptyline Omnibus Budget Reconciliation Act

depression and, 145–146, 148 (1987), 8
receptor affinities of, 134 Opioids, and chronic pain, 338
NSAIDs. See Nonsteroidal anti- Optimistic and supportive attitude, and
inflammatory agents treatment of older adults, 61
Nursing homes Oral contraceptives, and symptoms of
barriers to geriatric mental health depression, 79
care and, 9 Orbitofrontal syndrome, 335–336
health care for older adults and, 4–5 Organ systems, and biological aging,
substance abuse and, 329 52–54
Nutritional disorders, and dementia, Orientation-Memory-Concentration
190–191 Test (OMCT), 174, 177, 183,
382
Obesity, in older adults, 3 Overdose, and medication guidelines
Object Memory Evaluation, 188 for older adults, 61
Obsessive-compulsive disorder Oxazepam
diagnosis of, 279–281, 282 anxiety disorders and, 290, 291
prevalence of, 273 insomnia and, 318
treatment of, 289–290, 292, 293 Oxycodone, 328
Olanzapine
Alzheimer’s disease and, 216, 217, Pain. See Chronic pain
220 Panic disorder and panic attack
bipolar disorder and, 163 autonomic and psychomotor
delirium and, 264 features of, 275
psychosis and, 302–303, 304 diagnosis of, 281, 283
vascular dementia and, 248 prevalence of, 273
Older adults. See also Age and aging; treatment of, 292–293
Very old people Parkinsonism, and dementia with Lewy
barriers to mental health care for, 8– bodies, 237, 238, 239
12 Parkinson’s disease
definition of, 21–22 dementia and, 251, 253
health and functioning of, 3–6 depression and, 76
increase in population of, 1–2 Paroxetine
mental disorders in later life and, 6– depression and, 139, 142
8, 9 frontotemporal dementia and, 235
working effectively with, 15–16 receptor affinities of, 134
Patchiness, of cognitive deficits in psychiatric illness related to a

vascular dementia, 243 general medical condition and,
Pathogenesis and pathology. See also 334–336
Etiology Personality disorders, influence of aging
anxiety disorders and, 286–288 on early-onset forms of, 340–341
bipolar disorder and, 115–116 Personal qualities, for effective work
delirium and, 262 with elderly patients, 16
dementia with Lewy bodies and, Pharmacokinetic and psychodynamic
240 changes, and medications for older
frontotemporal dementia, 234–235 adults, 57–58
psychosis and, 298–300 Phencyclidine, and psychosis, 300
vascular dementia and, 246–247 Phenelzine, and depression, 150, 152
Patient Health Questionnaire (PHQ- Phenothiazines, 78
9), 102, 105 Phenylephrine, 328
Patient history Phenylpropanolamine, 328
Alzheimer’s disease and, 199–202 Phobias
delirium and, 257 diagnosis of, 278–279
dementia with Lewy bodies and, prevalence of, 273
238 Phosphodiesterase-5 inhibitors, 333
frontotemporal dementia and, Physical examination. See Medical
231 evaluation
general dementia and, 173 Physicians. See Primary care physicians
vascular dementia and, 242 Physostigmine, and delirium, 263,
Patient Self-Determination Act of 264
1990, 349–350 Pick’s disease, and dementia, 252
Penile prosthesis, 334 Pittsburgh Compound-B (PIB), 204
Penn State Worry Questionnaire, Population, increase of older adults as
276 percentage of, 1–2
Pension programs, and financial status, Positron emission tomography (PET)
45 and Alzheimer’s disease, 201, 203,
Pentobarbital, and insomnia, 318 204, 250
Perceptual changes, in normal aging, 24 and dementia, 185
Perphenazine, 304 and dementia with Lewy bodies,
Personality 237
changes of in normal aging, 38–43 and Parkinson’s disease, 251
cognition in normal aging and, 29 Poststroke depression, 73
Index 413
Posttraumatic stress disorder (PTSD), Probate, and surrogate decision-makers,

281–283, 284–285 363–365
Poverty, among elderly, 45 Problem-solving therapy, for geriatric
Power of attorney, 350, 363, 365 depression, 128
Prednisone, 79 Problem Solving Treatment in Primary
President’s Commission for the Study Care (PST-PC), 131
of Ethical Problems in Medicine Processing speed, and cognitive
and Biomedical and Behavioral abilities, 23, 27
Research (1982), 348 Professional approaches, for effective
Pretreatment evaluation, for lithium work with elderly patients, 16
therapy, 165–166 Prognosis, for elderly patients with
Prevalence. See also Epidemiology delirium, 264
of age-associated memory Progressive nonfluent aphasia, 231
impairment, 35 Propentofylline, and vascular dementia,
of alcohol abuse and dependency, 247–248
320–321 Propoxyphene, 328
of Alzheimer’s disease, 7, 193 Propranolol, 78
of anxiety disorders, 273 Prospective memory, 30
of delirium, 256–257 Protective factors
of frontotemporal dementia, 229 for Alzheimer’s disease, 192–195
of major depression, 80 for suicidality, 107
Prevention, of vascular dementia, Proxy directives, 350–351
247 Pseudodelirium, 262
Primary aging, 49, 50, 52–54 Psychiatric illness related to a general
Primary care physicians. See also Health medical condition, 334–337
care Psychiatrists. See also Mental health
alcohol abuse and, 325 professionals
assessment of suicidality and, 106 barriers to geriatric mental health
barriers to geriatric mental health care and, 11
care and, 10–11 working effectively with older
competency to drive and, 369, 371 adults, 15–16
elder abuse and, 372–373 Psychodynamic theories
Primary dysthymia, 91 of anxiety disorders, 286
Primary insomnia, 315, 316 of bipolar disorder, 115
Probable Alzheimer’s disease, 198–199, of depression, 108
203 of psychosis, 298–299
Psychological tests, and depression, 96– neuropsychological tests for, 296–

97. See also Neuropsychological 297
tests pathogenesis of, 298–300
Psychopharmacotherapy. See also risk factors for, 294
Antidepressants; Antipsychotics; subsyndromal depression and, 93
Anxiolytic agents; Augmentation; treatment of, 248, 300–306
Benzodiazepines; Beta-blockers; vascular dementia and, 248
Dosage; Drug-drug interactions; Psychosocial theory, of Alzheimer’s
Maintenance treatment; disease, 208–210
Medications; Monoamine oxidase Psychosocial therapy
inhibitors; Mood stabilizers; for anxiety disorders, 288–290
Psychostimulants; Sedative- for bipolar disorder, 162–163
hypnotics; Selective serotonin for late-onset psychosis, 300–302
reuptake inhibitors; Side effects; Psychostimulants
Treatment advantages and disadvantages of,
for alcohol abuse or dependency, 137
325–326 Alzheimer’s disease and, 219
for Alzheimer’s disease, 213–220 anxiety symptoms induced by,
for anxiety disorders, 290–293 277
for bipolar depression, 157 depression and, 153
for bipolar disorder, 163–166 Psychotherapy. See also Cognitive-
for delirium, 263–264 behavioral therapy; Family
electroconvulsive therapy and, therapy; Group therapy;
158 Psychosocial therapy; Supportive
for geriatric depression, 132–156 therapy; Treatment
for insomnia, 317–320 age-related cognitive changes and,
for late-onset psychosis, 302–306 34–35
for psychotic depression, 156 for alcohol abuse or dependency,
Psychosis. See also Psychotic depression; 325
Psychotic disorder due to a general for Alzheimer’s disease, 210
medical condition; Schizophrenia for dementia caregivers, 210–213
clinical presentation of, 294, 296 for geriatric depression, 127–130
differential diagnosis of, 298, 337 guidelines for treatment of older
epidemiology of, 293–294 adults and, 56
medications for agitation in research on for depression, 130–132
Alzheimer’s disease and, 220 Psychotic depression, 83–85, 156
Index 415
Psychotic disorder due to a general Religion, and social context of aging,

medical condition, 336–337 48
PTSD (posttraumatic stress disorder), Reminiscence therapy
281–283, 284–285 for Alzheimer’s disease, 209
Public health, and depression in later for geriatric depression, 130
life, 67 Remote memory, 30, 357–358
Repetitive transcranial magnetic
Quality of life, and anxiety disorders, stimulation (rTMS), and
274 depression, 159
Quetiapine Research
Alzheimer’s disease and, 216, 217, competency to enroll in studies,
220 352, 353
dementia with Lewy bodies and, on psychotherapy for geriatric
241 depression, 130–132
psychosis and, 303, 304 Reserpine, 78
Resources for Enhancing Alzheimer’s
Race, and diversity in patterns of health Caregiver health (REACH), 211,
and aging, 12–14, 29. See also 212
Black Americans; Hispanic Respiratory system, and biological
Americans aging, 52
Ranitidine hydrochloride, 79 Restatement of the Law Second, Contracts
Rating scales. See also 2d (American Law Institute
Neuropsychological tests; 1981), 353–354
Standardized tests Reversible dementia, 255–256
for activities of daily living, 184 Revised Memory and Behavior
for anxiety disorders, 274 Problems Checklist, 386–387
for cognitive impairment, 174–183 Revised NEO Personality Inventory
for depression, 97–105 (NEO-PI-R), 98
for frontotemporal dementia, 232– Risk factors
233 for alcohol abuse or dependency,
Recent memory, 30 321
Recovery phase, of bereavement, 69 for Alzheimer’s disease,
Referrals, for geriatric mental health 192–195
care, 10 for major depression, 80
Relaxation training, for obsessive- for suicidality, 106, 107
compulsive disorder, 290 for vascular dementia, 242
Risperidone Selective serotonin reuptake inhibitors

Alzheimer’s disease and, 216, 217, (SSRIs)
220 Alzheimer’s disease and, 219
anxiety disorders and, 292 anxiety disorders and, 293
bipolar disorder and, 163 bipolar depression and, 157
psychosis and, 302, 304 geriatric depression and, 133, 136,
vascular dementia and, 248 138–145, 148
Rivastigmine heart disease and, 72
Alzheimer’s disease and, 215, 218 sexual dysfunction and, 332
dementia with Lewy bodies and, Selegiline
241 Alzheimer’s disease and, 214
frontotemporal dementia and, 235 depression and, 150, 151, 152
vascular dementia and, 247 Self-help materials
Rorschach Inkblot Test, 99, 285–286 Alzheimer’s disease and, 213
depression and, 161
St. John’s wort, and depression, 161 memory function in old age and,
Schizoid disorder, 340–341 31–32
Schizophrenia. See also Psychosis Self-report scales, for depression, 100,
aging and early-onset, 339 104–105
anxiety and, 285–286 Semantic dementia, 231
diagnostic criteria for, 295 Senile plaques, and Alzheimer’s disease,
Screening instruments, for 206
frontotemporal dementia, 232– Sensory changes. See also Visual acuity
233. See also Rating scales normal aging and, 24, 54
Seattle Longitudinal Study, 22 treatment of depression and,
Secobarbital, 318 128
Secondary aging, 49 Serotonin system, and pathogenesis of
Secondary dysthymia, 91 anxiety disorders, 288
Sedative-hypnotics. See also Hypnotic Sertraline
agents anxiety disorders and, 292–293
insomnia and, 318 depression and, 139, 142, 148
substance abuse and, 326, 328 receptor affinities of, 134
symptoms of depression induced by, Setting, for treatment of older adults,
78 58–59
Seizure disorders, and secondary mania, Sexual dysfunction, 329–334
112 Short-term memory, 28
Index 417
Sibling relationships, and social context Somatization disorder, 86

of aging, 47 Somnolent or hypoactive subtype, of
Side effects, of medications delirium, 258
antidepressants for geriatric Space-occupying lesions, and dementia,
depression and, 148–149 191
antipsychotics and atypical Specific phobia, 280
antipsychotics, 304–305 Spielberger State-Trait Anxiety
guidelines for treatment of older Inventory, 274, 275
adults and, 60 Stage theories, of personality, 39–40
lithium and, 166 Standardized tests, of decisional
monoamine oxidase inhibitors and, competency, 358. See also Rating
152 scales
Sildenafil, 333 Statins, and Alzheimer’s disease, 194–195
Simple consent, 349 Steroids, and medication-induced
Single photon emission computed mental disorders and, 56, 79
tomography (SPECT) Stroke
and Alzheimer’s disease, 201, 203– depression following, 73
204, 250 vascular dementia and, 242
and dementia with Lewy bodies, Substance abuse. See also Alcohol and
237 alcohol abuse
and frontotemporal dementia, 234 common patterns of, 327
Situational anxiety, 276 diagnostic criteria for, 322, 323
Six-Item Orientation-Memory- distinguishing substance use from,
Concentration Test, 174, 177, 327–328
183, 382 epidemiology of, 326–327
Sleep disturbance. See also Insomnia prescription of potentially addictive
dementia with Lewy bodies and, substances and, 330
237 substance-induced mood disorder
major depression and, 83 and, 77
sleep apnea, 315 treatment of, 328–329
Sleep evaluation, and depression, 96 Substance-induced insomnia, 315
Social clock, 39 Substance-induced mania, 111, 112
Social context, of aging, 43–48 Substance-induced mood disorder, 76–
Social Security, 21, 43–44, 45 80
Somatic complaints, and major Substance-induced persisting dementia,
depression, 83, 85 254–255
Substitute decision makers, 350, 351– Theophylline, and electroconvulsive

352 therapy, 158
Substituted judgment, doctrine of, 350 Thiazide diuretics, and depression, 78
Subthreshold depression, 92–95 Thioridazine, 217, 304
Suicide and suicidality Thiothixene, 304
anxiety disorders and, 274, 278 Thyroid function, and depression, 96
assessment of in elderly, 105–106, Time course, of normal grief, 69
107 Tocopherol forms, and Alzheimer’s
Supportive therapy disease, 194
for Alzheimer’s disease, 210 Toxins, and dementia, 191
for late-onset psychosis, 301–302 Trail Making Test (TMT), 189, 368
Surrogate decision-makers, 363–365 Tramadol, 338
Sydenham’s chorea, 335 Tranylcypromine, and depression, 150–
Sympathomimetics, and anxiety, 277 151, 152
Systemic disorders, and dementia, Trazodone
191 advantages and disadvantages of,
136
Tacrine, 213 Alzheimer’s disease and, 216, 217,
Tadalafil, 333 220
Target symptoms, and treatment of depression and, 138, 146
older adults, 59 frontotemporal dementia and, 235
Tau-positive pathology, of insomnia and, 320
frontotemporal dementia, 235 receptor affinities of, 134
Telomeric shortening, 49–50 sexual dysfunction and, 332
Temazepam Treatment, of mental disorders in older
insomnia and, 318 adults. See also Clinical
pharmacological properties of, implications; Combined
291 treatment; Compliance;
Testamentary capacity, 354–356 Medications;
Testosterone, and treatment of sexual Psychopharmacotherapy;
dysfunction, 332–333 Psychotherapy; Undertreatment
Texas, and elder abuse, 372 of anxiety disorders, 288–293
Texas Medication Algorithm Project, of bipolar disorder, 162–166
156 of delirium, 263–264
Thematic Apperception Test (TAT), of dementia with Lewy bodies, 240–
99, 285–286 241
Index 419
of erectile dysfunction, 335 Uniform Probate Code, 361

of frontotemporal dementia, 235 U.S. Preventive Services Task Force,
guidelines for, 55–61 105, 372
of hypomania and mania, 162 Useful Field of View (UFOV), 368
of insomnia, 315–320
of late-onset psychosis, 300–306 Vagus nerve stimulation, and
of psychotic disorder due to a depression, 160
medical condition, 337 Valproate, and Alzheimer’s disease, 220
of sexual dysfunction, 332–334, Valproic acid, and Alzheimer’s disease,
335 218, 219
of substance abuse, 328–329 Vardenafil, 333
of vascular dementia, 247–248 Vascular dementia
Treatment resistance, and clinical presentation of, 243
antidepressants, 153–155 depression and, 73–74
Triazolam, and insomnia, 317–318 diagnosis of, 241–242, 243
Tricyclic antidepressants (TCAs). differential diagnosis of, 245–246,
See also Antidepressants 250
advantages and disadvantages of, epidemiology of, 241
136 laboratory evaluation of, 245
bipolar depression and, 157 neuropsychological tests and, 244–
geriatric depression and, 133, 138, 245
145–146, 149, 154 pathogenesis of, 246–247
psychotic depression and, 156 patient history in, 242
Trifluoperazine, 304 physical and neurological
Triiodothyronine, and augmentation of examinations for, 243–244
antidepressants, 155 prevention of, 247
Trusts, and competency, 356, 365 treatment of, 247–248
Twin studies, of Alzheimer’s disease, 208 Vascular depression, 74–76, 109
Vascular disorders, and dementia, 191
Underrecognition, of mental health Vascular lesions, and mania, 112
problems in older adults, 10 Venlafaxine
Undertreatment, mental health advantages and disadvantages of,
problems in older adults, 60, 136
67–68 depression and, 138, 144, 148
Undue influence, and question of receptor affinities of, 134
voluntariness, 358–360 sexual dysfunction and, 332
Very-late-onset schizophrenia-like Withdrawal, from medications

psychosis (VLOSLP), 294, 296, anxiety and, 277
297, 298, 301, 303 delirium and, 263
Very old people (85 years and older). guidelines for treatment of older
See also Age and aging adults and, 61
definition of “old-old” and, 21 Women
as percentage of population, 1 diversity in patterns of health and
Veterans Affairs, 73 aging, 14–15, 29
Visual acuity, and normal aging, 24, employment trends for, 44
368 personality changes during aging
Visuospatial ability, and aging effects on and, 39
cognitive performance, 27 poststroke depression in, 73
Vitamin B deficiency, and dementia, poverty and, 45
256 social context of aging and, 48
Vitamin C, and Alzheimer’s disease, vascular depression and, 75
194 very-late-onset schizophrenia-like
Vitamin E, and Alzheimer’s disease, psychosis and, 294
194, 214 widowhood and, 45–47
Voluntariness, and undue influence, Women’s Health Initiative Memory
358–360 Study, 194
Voluntary consent, 352 Word List Learning, and Alzheimer’s
disease, 203
Web sites, for information Work, and social context of aging, 43–
on Alzheimer’s disease, 213 45
on elder abuse, 373 Working memory, 23–24, 28
Wechsler Adult Intelligence Scale, 28, Worry Scale, 274, 275
187, 357
Wechsler Memory Scale, 187 Xanthine derivatives, and anxiety, 277
Widowhood, and social context of
aging, 45–47 Zaleplon, and insomnia, 318, 319–320
Wills, and competency, 354–356. See Ziprasidone
also Living will bipolar disorder and, 163
Will substitution test, and undue dementia with Lewy bodies and,
influence, 359 241
Wisconsin Card Sorting Test, psychosis and, 303, 304
189 Zolpidem, and insomnia, 318, 319–320

Geriatric Psychiatry

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Asenath La Rue, Ph.D.

4 Mood Disorders—Treatment . . . . . . . . . . . . . . . 127

6 Other Dementias and Delirium . . . . . . . . . . . . 229

8 Other Common Mental Disorders

9 Competency and Related Forensic Issues. . . . 347

Appendix: Clinical Assessment

Worldwide, average life expectancy has increased to about 65 years (Cohen

Health and Functioning of Older Adults

Figure 1–3. Percentage of Medicare enrollees age 65 and older, by type of

Mental Disorders in Later Life

Older patients experience the same broad spectrum of mental disorders as

Barriers to Geriatric Mental Health Care

Table 1–1. Mental disorders among older adults

Cognitive impairment 4.9 30.2

adults has been more thoroughly confirmed (Chapters 4 through 8, “Mood

• Multiple medical illnesses in elderly patients may divert physicians’ attention

A probability survey of primary care providers found that only 6% of gen-

questionnaires or other structured procedures to screen for depression in their

Diversity in Patterns of Health and Aging

• Continuing research to establish the efficacy of evidence-based treatments

Table 1–2. Knowledge needed to work effectively with elderly

medical or mental conditions (e.g., heart disease, Alzheimer’s disease), and

Working Effectively With Older Adults

Table 1–3. Personal qualities and professional approaches

Cross-Sectional and Longitudinal Views

Heterogeneity in Patterns of Aging

Cognitive Abilities in Later Life: A Processing

backward as opposed to forward). Reductions in working memory, in turn,

Sensory and Perceptual Changes

Neuropsychological Explanations of Cognitive Aging

General Aging Trends

26 Clinical Manual of Geriatric Psychiatry

Factors That Influence Cognitive Aging

Learning and Memory

Anecdotally, remote or long-term memory is well maintained in old age.

Effect of Cognitive Change on Everyday Function

Clinical Implications of Cognitive Change

Abrupt changes in cognitive function always warrant medical attention.

Diagnosing Age-Related Cognitive Change and Mild

other cognitive areas, such as language, visuospatial skills, or reasoning. The

Table 2–3. Clinical presentations of memory loss in old age

Clinical Memory complaint Memory complaint or memory

portion have Alzheimer-type brain changes on autopsy (Morris et al. 2001).

tia symptoms or preventing their progression. Also, effective prevention of

Personality and Emotional Changes

Coexisting Stability and Change

Influences on Adult Personality

Personality and Perceptions of Health

Emotions, Coping, and Well-Being

on emotion-focused forms of coping, as opposed to active, problem-solving

An influential model of adult development that has emerged in recent

Clinical Implications of Personality and

Core features of personality remain stable throughout adulthood, and any

Increasing salience of emotional matters can influence assessment, espe-

Social Context of Aging

Education, Work, and Financial Status

100 High school graduate or higher

Figure 2–1. Educational attainment of Americans age 65 and older,

Marriage and Widowhood