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Blood pressure and your brain

Hypertension is a circulatory disease. Many patients with high blood pressure develop
coronary artery disease or heart failure, and many die as a result. But all parts of the
body depend on the circulation, and many organs suffer from the impact of untreated
hypertension. One of the organs at greatest risk is the brain.

High pressure, high risk
High blood pressure is the leading cause of strokes, both symptomatic and silent. Both
systolic and diastolic hypertension contribute to risk; the higher your pressure, the
higher your risk. According to one Harvard study, hypertension increases a man's risk of
stroke by 220%; according to another, each 10 mm Hg rise in systolic pressure boosts
the risk of ischemic stroke by 28% and of hemorrhagic stroke by 38%.
That's the bad news. The good news is that treating hypertension is extremely
protective; in round figures, if you reduce your systolic blood pressure by 10 mm Hg,
you should cut your risk of stroke by a whopping 44%.

Losing it
Mental decline is one of the most feared consequences of aging. But although many
senior citizens experience some changes in memory as they grow older, most men who
remain healthy continue to function at high levels. They learn to compensate for minor
changes in the speed of recall and to use the wisdom that has accumulated over the
years to maintain the ability to reason and think creatively.
Unfortunately, many men don't stay healthy, and many develop cognitive dysfunction. A
variety of illnesses and medications can contribute to cognitive dysfunction and as
research continues to come in, it's increasingly clear that hypertension takes a toll on
the aging brain.
Mild cognitive impairment can be a problem, but it's usually quite manageable. But
severe memory loss is a disaster; you may think of it by its old name, senility, but
doctors now use the term dementia to characterize these severe disturbances of
memory, reasoning, and judgment. Although dozens of neurological diseases can
cause dementia, just two account for the lion's share, multi-infarct or vascular dementia
and Alzheimer's disease.
Multi-infarct dementia occurs when small vessels in the brain become diseased or
blocked, depriving brain cells of the oxygen and glucose they need. f enough nerve
cells are damaged or killed by the process, memory can't be restored.
Alzheimer's disease is different. The problem begins with the accumulation of beta-
amyloid, a small sticky protein that interferes with the function of nerve cells and
eventually kills off cells, leaving neuritic plaques in its wake. n advanced disease, brain
cells become clogged with neurofibrillary tangles composed of a protein called tau. n
most cases, the part of the brain that is responsible for memory (the hippocampus) is hit
the hardest.
One size does not fit all
Patients with hypertension often have additional medical problems that influence the
choice of a blood pressure medication. Here are some conditions that may benefit from
a specific class of medication; in every case, a physician should choose the medication
that's best for that particular patient.
Compelling indicators for blood pressure drugs
Condition Useful medications
Diabetes ACE, ARB
Previous heart attack BB, ACE, ARB
Previous stroke Diuretic, ACE, ARB
Kidney disease ACE, ARB
High risk of coronary artery disease Diuretic, BB, CCB, ACE, ARB
ACE = angiotensin-convertingenzyme inhibitor
BB = beta blocker
ARB = angiotensin-receptor blocker
CCB = calcium-channel blocker

High pressure, short memory
Since hypertension damages blood vessels, it's easy to see how it contributes to
vascular dementia. Although the link to Alzheimer's disease is less obvious, research
suggests that vascular damage and tissue inflammation accelerate injury.
The details vary from study to study, but the weight of evidence now suggests that high
blood pressure increases the risk of mild cognitive impairment, vascular dementia, and
even Alzheimer's disease. Both systolic and diastolic hypertension take a toll; in
general, the higher the pressure and the longer it persists without treatment, the greater
the risk.
Most investigations focus on older adults. For example, a study of 2,505 men between
the ages of 71 and 93 found that men with systolic pressures of 140 mm Hg or higher
were 77% more likely to develop dementia than men with systolic pressures below 120
mm Hg. And a study that evaluated blood pressure and cognitive function in people
between 18 and 46 and between 47 and 83 found that in both age groups high systolic
and diastolic pressures were linked to cognitive decline over time.
Doctors may be able to help ease the burden of dementia, but the damage and
disability cannot be reversed. That makes prevention doubly important. Can treating
hypertension help prevent dementia?
Yes. European scientists reported that long-term antihypertensive therapy reduced the
risk of dementia by 55%. Several American studies are only slightly less optimistic. One
linked therapy to a 38% lower risk. Another reported that each year of therapy was
associated with a 6% decline in the risk of dementia; in particular, men treated for 12
years or more enjoyed a 65% lower risk of Alzheimer's disease than men with untreated
hypertension. Another study of American men and women linked therapy to a 36%
reduction in the risk of Alzheimer's disease; diuretics appeared to be the most beneficial
medication. And a team of investigators from Harvard and Boston University reported
that six months of antihypertensive therapy actually improves blood flow to the brain,
providing a good explanation for the benefits observed in clinical studies.

Never too late
t's good to know that blood pressure control can reduce the risk of cognitive
dysfunction. But what about men who already have mild memory loss? Can treating
hypertension help stave off further damage?
Perhaps. talian scientists studied 80 patients with mild cognitive dysfunction. Over a
two-year period, patients who were given antihypertensive medications were 80% less
likely to progress to full-blown Alzheimer's than untreated patients. t's only one study,
and a small one at that. And let's hope scientists don't forget to follow up with additional
research.

Getting control
For your head as well as your heart, get your blood pressure down. And even if you
forget that hypertension is bad for your brain, remember that men with normal blood
pressures live about five years longer than hypertensive men.
The first step is to know your blood pressure. t seems obvious, but more than 20% of
people with hypertension don't know they have the disease.
The next step is to know your goal. Even if you are just in the prehypertensive range,
you should try to bring your pressure down to a normal reading below 120/80. People
with hypertension can use somewhat less stringent goals; if otherwise healthy, a target
below 140/90 is reasonable. But for patients with diabetes, chronic kidney disease,
coronary artery disease, peripheral artery disease, carotid artery disease, or abdominal
aortic aneurysm, the goal is below 130/80.
Third, live right. Lifestyle modification can lower your blood pressure. t's an essential
part of the treatment for everyone with hypertension and since lower pressures are
better for health, it's an excellent plan for anyone with a pressure above 115/70. Here
are five steps that can help:
1. Diet. Reduce your sodium intake to less than 2,300 mg a day; 1,500 mg is the new,
though stringent, goal for people with hypertension and for totally healthy folks who are
middle-aged and older. Reduce your intake of animal fat and processed foods, but chow
down lots of fruits, vegetables, whole grains, fish, and non- or low-fat dairy products. A
good diet can lower systolic blood pressure by 10 to 22 mm Hg.
2. Exercise. Moderate exercise is excellent, even outperforming intense exercise in
some studies. Walking for 30 minutes a day is one way to lower your systolic pressure
by 4 to 9 mm Hg or more.
3. Weight control. Diet and exercise will get you there. An obese person who sheds 20
pounds can expect a drop of 5 to 20 points in blood pressure over and above the
benefits of diet and exercise.
4. Moderate alcohol use. Light to moderate drinking to the tune of one to two drinks a
day won't raise your blood pressure, but heavy drinking will.
5. Use nonsteroidal anti-inflammatory drugs (NSADs) judiciously. Long-term use of
NSADs (ibuprofen, naproxen, others) can raise blood pressure, particularly in older
people.
6. Stress control. t's easier said than done in today's hectic world, but winding down
can help you keep your pressure down.
Finally, use medications if you need more help. t's another point that should be
obvious, but a shocking 55% of hypertensive patients are above their targets. The
authoritative JNC7 report recommends thiazide diuretics, ACE inhibitors, angiotensin-
receptor blockers, calcium-channel blockers, and beta blockers as first-line medications,
but research suggests beta blockers may be less desirable than the others, particularly
to prevent strokes. Many experts start with a thiazide diuretic, but if you have particular
needs, another drug may be best (see box above). And a combination of two or more
drugs is often needed.
Cooperate with your family to improve your lifestyle, and work with your doctor to find
the medication that will bring you to your target blood pressure safely. t will take
patience and persistence, but it's the brainy thing to do.
Research suggests high blood pressure increases risk of cognitive impairment, reports
the Harvard Men's Health Watch
OCTOBER 2009
High blood pressure is hard on the heart and blood vessels. t's also bad for the brain,
reports the October 2009 issue of Harvard Men's Health Watch.
A growing body of research indicates that high blood pressure, more formally known as
hypertension, takes a toll on the aging brain. Although the details vary from study to
study, the weight of the evidence suggests that high blood pressure increases the risk
of mild cognitive impairment, vascular dementia, and even Alzheimer's. Treating high
blood pressure can reduce the risk of these feared consequences of aging.
Hypertension is also the leading cause of brain-damaging strokes. According to one
study, hypertension increases a man's risk of stroke by 220%. The good news is that
treating hypertension is extremely protectivelowering the first number of your blood
pressure reading (your systolic pressure) by 10 points reduces your risk of stroke by
44%.
The Harvard Men's Health Watch recommends that for your head, as well as your heart,
it's important to get your blood pressure down. Try these lifestyle modifications to lower
your blood pressure:
Diet. Reduce your sodium intake to less than 2,300 mg a day (or 1,500 mg if you have
hypertension or are middle-aged or older). Reduce your intake of animal fat and
processed foods. Eat lots of fruits, vegetables, whole grains, fish, and non- or low-fat
dairy products.
Exercise. Moderate exercise can help control blood pressure.
Weight. Shedding 20 pounds can lower blood pressure 5 to 20 points.
Alcohol. One to two drinks a day is okay, but heavy drinking can boost blood pressure.
Stress. Winding down helps keep press
Medications found to cause cognitive impairment of aging brain
Drugs commonly taken for a variety of common medical conditions including insomnia,
allergies, or incontinence negatively affect the brain causing long term cognitive
impairment in older African-Americans, according to a study appearing in the July 13,
2010 print issue of Neurology, the medical journal of the American Academy of
Neurology.

These drugs, called anticholinergics, block acetylcholine, a nervous system
neurotransmitter, and are widely-used medical therapies. They are sold over the
counter under various brand names such as Benadryl, Dramamine, Excedrin PM,
Nytol, Sominex, Tylenol PM, and Unisom. Other anticholinergic drugs, such as
Paxil, Detrol, Demerol and Elavil are available only by prescription. Older adults
most commonly use drugs with anticholinergic effects as sleep aids and to relieve
bladder leakage problems.

Researchers from ndiana University School of Medicine, the Regenstrief nstitute and
Wishard Health Services conducted a six-year observational study, evaluating 1,652
ndianapolis area African-Americans over the age of 70 who had normal cognitive
function when the study began. n addition to monitoring cognition, the investigators
tracked all over-the-counter and prescription medications taken by study participants.

"We found that taking one anticholinergic significantly increased an individual's risk of
developing mild cognitive impairment and taking two of these drugs doubled this risk.
This is very significant in a population - African-Americans - already known to be at high
risk for developing cognitive impairment," said Noll Campbell, PharmD, first author of
the study. Dr. Campbell is a clinical pharmacist with Wishard Health Services.

"Simply put, we have confirmed that anticholinergics, something as seemingly benign as
a medication for inability to get a good night's sleep or for motion sickness, can cause or
worsen cognitive impairment, specifically long-term mild cognitive impairment which
involves gradual memory loss. As a geriatrician tell my Wishard Healthy Aging Brain
Center patients not to take these drugs and encourage all older adults to talk with their
physicians about each and every one of the medications they take," said Malaz
Boustani, M.D., U School of Medicine associate professor of medicine, Regenstrief
nstitute investigator and U Center for Aging Research center scientist.

"The fact that we found that taking anticholinergics is linked with mild cognitive
impairment, involving memory loss without functional disability, but not with Alzheimer
Disease, gives me hope. Our research efforts will now focus on whether anticholinergic-
induced cognitive impairment may be reversible," said Dr. Boustani, who added that
"this study offers a new window to change the burden of dementia" for the individual,
the caregiver and the healthcare system."

"This finding of a link between anticholinergics and long term mild cognitive impairment
complements our previous work which confirmed a link between anticholinergics and
delirium, which is a sudden onset cognitive impairment," said Dr. Campbell.

Although this study, which was funded by the National nstitute on Aging, looked at only
African-Americans, both Dr. Campbell and Dr. Boustani believe future studies will find
that the results are generalizable to other races.
(http://www.scientistlive.com/European-Science-
News/Pharmacology/Medications_found_to_cause_cognitive_impairment_of_aging_bra
in)

Type 2 Diabetes Linked to Mild Cognitive mpairment
News Author: Caroline Cassels
CME Author: Charles Vega, MD, FAAFP

April 12, 2007 A study shows individuals with type 2 diabetes have a significantly
increased risk of developing amnestic mild cognitive impairment (MC), a condition
widely acknowledged as a transitional state between normal cognitive functioning and
Alzheimer's disease (AD).
n a longitudinal study appearing in the April issue of the Archives of Neurology, elderly
individuals with type 2 diabetes were found to be at greater risk for MC overall and for
amnestic MC impairment specifically compared with their counterparts without
diabetes.
"n our analyses, diabetes was related to a higher risk of amnestic MC even after
adjusting for stroke and vascular risk factors, which suggests that the association
between diabetes and amnestic MC is independent of cerebrovascular disease," Jos
A. Luchsinger, MD, from the Columbia University Medical Center in New York, and
colleagues write.
Conversely, the authors note, the association between diabetes and nonamnestic MC
lessened and became nonsignificant after adjustment for stroke and vascular risk
factors. This finding suggests cerebrovascular disease may mediate the relation
between diabetes and nonamnestic MC, the authors say.
Attenuated Risk
The study included 918 individuals aged 65 years or older without MC or dementia at
study entry who were residing in northern Manhattan.
Baseline data, which included an in-person interview about general health and function,
followed by a standard assessment, medical history, physical and neurologic
examinations, and neuropsychological testing, were gathered between 1992 and 1994.
With an average 6.1 years of follow-up, study participants were assessed every 18
months until 2003. During this period 334 individuals developed MC: 160 amnestic
cases and 174 nonamnestic cases.
Multivariate analyses revealed diabetes was related to a higher risk for all-cause MC
even after adjusting for age, sex, ethnic group, years of education, apolipoprotein E
(APOE) s4, hypertension, low-density lipoprotein cholesterol level, heart disease,
stroke, and current smoking.
When only nonamnestic MC was considered, type 2 diabetes became nonsignificant
after adjusting for ethnic group, years of education, and APOE s4, n addition, the risk
was further attenuated after investigators adjusted for other vascular risk factors, heart
disease, and stroke.
n contrast, adjusted analyses did not change the association between type 2 diabetes
and amnestic MC risk.
"The risk of MC attributable to diabetes was 8.8% for the whole sample, 8.4% for
African-American persons, 11.0% for Hispanic persons, and 4.6% for non-Hispanic
white persons, reflecting the differences in diabetes prevalence by ethnic group," the
authors write.
Possible Mechanisms
According to the investigators, there are several possible mechanisms at play that may
explain the link between type 2 diabetes and amnestic MC among them, the
hypothesis that diabetes may directly affect amyloid accumulation, the hallmark of AD.
"Hyperinsulinemia, which can precede and accompany diabetes, may disrupt brain
amyloid clearance by means of the insulin degrading enzyme. Another potential
mechanism is the generation of advanced products of glycosylation," Dr. Luchsinger
and colleagues write.
t also is possible, the authors note, that diabetes may be a risk factor for nonamnestic
forms of MC and cognitive impairment via cerebrovascular disease.
"Our results provide further support to the potentially important independent role of
diabetes in the pathogenesis of AD. Diabetes may also be a risk factor for non-amnestic
forms of MC and cognitive impairment, but our analyses need to be repeated in a larger
sample."
The National nstitutes of Health, the Charles S. Robertson Memorial Gift for Research
on Alzheimer's Disease, the Blanchette Hooker Rockefeller Foundation, and the New
York City Council Speaker's Fund for Public Health Research supported this study. The
authors have disclosed no relevant financial relationships.
Arch Neurol. 2007;64:570-575.
Clinical Context
Diabetes previously has been established as a risk factor for the development of
dementia. n a study of 2574 Japanese-American men by Peila and colleagues, which
was published in the April 2002 issue of Diabetes, the presence of clinical or laboratory-
diagnosed type 2 diabetes was associated with increased risks for total dementia, AD,
and vascular dementia, with increasing risks for each of these respective categories of
dementia. Diabetes and the presence of APOE were synergistic in increasing the risk
for dementia. Among a subset of patients who underwent autopsy, diabetes was
associated with a higher number of hippocampal neuritic plaques and neurofibrillary
tangles in the cortex and hippocampus.
MC has received attention as a possible precursor to AD. The current study by
Luchsinger and colleagues examines the relationship between clinical diabetes and
MC, and it concentrates on minority populations that are disproportionately affected by
both disorders.
Study Highlights
O Patients eligible for study participation were aged 65 years or older and lived in
northern Manhattan. Baseline medical interviews, physical and neurologic
examinations, and neuropsychological batteries were completed between 1992
and 1994. Patients without dementia or MC at baseline were eligible to continue
in the study.
O Subjects were evaluated every 18 months with repeat neuropsychological
testing. Dementia was diagnosed based on criteria from the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, criteria, and AD also was
diagnosed with standard criteria.
O MC was diagnosed by the presence of memory complaints, objective impairment
in at least 1 cognitive domain, and preserved activities of daily function. The
authors further categorized subjects with a positive screening evaluation for MC
as having amnestic MC or nonamnestic MC. Amnestic MC is considered to
precede AD, whereas nonamnestic MC may be more associated with vascular
dementia.
O The main study result was the relationship between diabetes and MC. This
result was adjusted for multiple confounders, including APOE genotypes.
O 918 participants had data available for analysis. Their mean age was 75 years,
and approximately 70% of the cohort were women. Nearly half of the study
cohort were Hispanic, with a large proportion of Dominican subjects, and
approximately one third of the cohort were African American.
O 23.9% of subjects had diabetes. Persons with diabetes were generally younger
and more likely to be Hispanic vs patients without diabetes.
O There were 160 cases of amnestic MC and 175 cases of nonamnestic MC
diagnosed during 5556 person-years of follow-up. After adjustment for potential
confounders, diabetes increased the risk for incident MC by a hazard ratio of
1.4. This risk was similar when considering only amnestic MC, but there was no
significant association between the diagnosis of nonamestic MC and diabetes
after adjustment for all possible confounders.
O The presence of APOE s4 did not modify the relationship between diabetes and
MC.
O The risk for MC attributed to diabetes differed among ethnic groups (4.6% for
non-Hispanic whites, 8.4% for African Americans, and 11.6% for Hispanics),
reflecting the differences in prevalence of diabetes in these populations.
Pearls for Practice
O Previous research by Peila and colleagues has demonstrated that type 2
diabetes increases the risks for total dementia, AD, and vascular dementia, as
well as the risks for changes in neuroanatomy consistent with dementia.
Diabetes and the presence of APOE were synergistic in increasing the risk for
dementia in this cohort of men.
O The current study by Dr. Luchsinger and colleagues demonstrates that diabetes
increases the risk of developing MC, particularly amnestic MC. However,
diabetes did not have a significant effect on the risk for nonamnestic MC.
Diabetes is more prevalent among African Americans and Hispanics, and it
promotes MC to a greater degree in these ethnic groups

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