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OUTLINE
Introduction
How to Differentiate Vascular VaD
AD
Dementia and Alzheimer
Differential Diagnosis
Silvia F. Lumempouw MD MMSE
National Brain Center Hospital
Jakarta

Dementia
The total number of people with dementia worldwide in 2010 is
estimated at 35.6 million and is projected to nearly double every 20
years, to 65.7 million in 2030 and 115.4 million in 2050.
The total number of new cases of dementia each year worldwide is
nearly 7.7 million, implying one new case every four seconds.
The World Health Organization (WHO) and Alzheimer's Disease
International (ADI) has urged governments around the world to
make dementia a priority public and social care nationally.
The priority areas of action that need to be addressed within the
policy and plan include raising awareness, timely diagnosis,
commitment to good quality continuing care and services, caregiver
support, workforce training, prevention and research.

Dementia: a public health priority

http://www.who.int/mental_health/publlcations/dementia_report_2012/en/

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lence of der ifintiai

World Health Organization (WHO). Dementia: a public health priority. Geneva: WHO; 2012
Indonesia
Elderly population in Indonesia has increased
significantly.
In 2007 the elderly population of 18.96 million,
increased to 20.547.541 in 2009. This amount includes
the 4th largest after China, India and Japan.
Life expectancy has increased dramatically, from 45 in
1970 to 69.2 for men and 71 for women in 2010. At the
same time, the birth rate has declined, resulting in an
ageing population.
World Health Organization predicts that the elderly
population in 2020 reached 11.34% or 28.8 million
people registered.
Penduduk Lanjut Usia.
http://storage.jak-stik.ac.id/ProdukHukum/MenPAN/index.php-o ption=com

Cognitive "continuum'
Normal
Cognition
Alzheimer Disease
Minjftgin
Vascular Dementia

Mild Cognitive . Frontotemporal Dementia

Impairment
Prodromal oj
Parkinson Dementia/DLDB

Depression

Dementia

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WHAT IS DEMENTIA:
Dementia is a syndrome o f :
- Acquired loss of cognitive function,
- Behavior changes
- Loss of social function
- Sufficient to interfere with the patient's
lifestyle.
Causes disability, lost of productivity,
health care cost to both patients and
caregiver

Vascular Dementia Criteria

Epidemiology . Clinical evidence of stroke :
ljiiiMiUi :
'"- Neurological examination or imaging".
Vascular dementia is the second most common cause of dementia in the . Temporal link not required :
United States and Europe, but it is the most common form in some parts
of Asia. . Clinical evidence of stroke '
The prevalence rate of vascular dementia is 1.5% in Western countries and - Neurological examination^ imaging.
approximately 2.2% in Japan. In Japan, vascular dementia accounts for . Temporal link required
50% of all dementias that occur in individuals older than 65 years.
In Europe, vascular dementia and mixed dementia account for
approximately 20% and 40% of cases, respectively.
In Latin America, 15% of all dementias are vascular. l NINDS-AIREN Criteria
In community-based studies in Australia, the prevalence rate for vascular
and mixed dementia is 13% and 28%, respectively. Probable Dementia and stroke with:
The prevalence rate of dementia is 9 times higher in patients who have VaO - *: Abrupt onset of dementia onset within 3 months ' '
had a stroke than in controls. One year after a stroke, 25% of patients VFIuctuacting or stepwise course
develop new-onset dementia. Within 4 years following a stroke, the ;:,"'>';': Y"- !:"'". ',-~t>i::-",''. "< /.
relative risk of incident dementia is 5.5%.
The prevalence of vascular dementia is higher in men than in women. Passible ': Dementia with focal neurological signs when :
Vab '..';" itNeuroimaging,not available ;;
.; Absence of cleartemporal relationship
/v: Subtle onset and variable course of cognitive deficit

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Alzheimer's Disease Diagnostic and

Criteria VaD
Treatment Centers (ADDTC) Criteria
The most widely used clinical diagnostic
mentia and:
2 strokes by history, neurological signs +/- criteria for VaD are the NINDS-AIREN criteria.
rieuroimaging or 1 stroke with a temporal relationship
with the onset of dementia- ; In a neuropathological series, the sensitivity of
I infarct outside the cerebellum byCTor MRI;
the NINDS-AIREN criteria for probable and
Dementia and one or more:
. ; 1 stroke without clearrelationship to onset
possible VaD was 58% and specificity was 80%
.'Binswanger's : -.. --.:. ,; '"',';,
;J? Early onset of gart disturbance or urinary
'j incontinence, vascular risk factors, and White
'";. : matter changes.

l : -. :- j S f e w V ^ i f
Subcortical Vascular Cognitive
iikr!ii^'!teteft ;.nt ImpairMglia
_ _.- _
The concensus is growing that small-vessel diseases have a
Reporting of subjective symptoms more important role in the field of VaD.
Objective confirmation by neurocognitive and - Subcortical ischaemic vascular dementia
(SIVD)
behavioral assessment
- In clinical studies, the proportion of SIVD ranges
Determination of severity from 36% to 67%.
The concept of VaD has been broadened to encompase all
Functional impact on ADL forms of cognitive loss due to CVD, under the nosology of
Vascular Cognitive Impairment (VCI). VCI includes with CVD.
- VCI no dementia (VCI-ND)
Strokes with normal
- Vascular Dementia
Cognitive impairment, Vascular
I cognition No Dementia Dementia
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Spect rum of Vascular Dementia . ...-

Vascular
Phanotypa:
Cerebrovascular Vascular Mechanism
Risk Factors Disease Distribution of Brain Injury

Modifiable Cerebrovascular Single Artery hebemit:

Hyped emion Atherosclerosis Urge artery Acuta;
HyperglycamU ArterloioKkrosts Small arteriole Thrombosis
Hyperlipidemia Amyloid angiopathy EmooUwi
Homocysteine Vasculitis Border Zona
Mixed dementia Smoking Tortuosity Large arteries Chronic
Obesity Anomaly Smalt arterioles Hypoperfusion
Inflammation Capillaries
Alzheimer's Binswanger's Cardiac Hernorrh*ge
Ncmmodlfiabl. Atrial fibrillation Venous
disease disease A Endocarditis Leaky Biood^
Gender Myopathy Capillary fcaktBanfar
Estrogen Mural thrombus
Race Anoxfa
Heredity Blood Content
CADASIL Hypoglycemia
CARA5IL Hypoxemia
Vascular risk factors HCHWA-0 Hemoglobinopathy
HCKWA-I Coagulopathy

CAOASJt m cerebral eutowjmai ckxrorvanl arthropathy wrth subcortical infarcts and leukc*i<ephAtopaihy; CARASa. -
cerebral autosomal retesMv* Jrtertopaihy with subcortical Infarcts and ieuioeiKepralopathyj KHWA-D ruereoilary
<m**alrieiTx>rt,_oflv.rtlharc,^^ nytadosis, koeUndk: type.
iVpntMO vath p*mwicn IHTP CnU HC. V * K I ^ _ 4 ^ ^
MO0jt.lt-97(.Ccpn_r^ v * i penrHW> tram Us****

Vascular dementia symptoms

The spectrum of vascular dementia
include:
Confusion
(1) mild vascular cognitive impairment, (VCIND) Trouble paying attention and concentrating
(2) multi-infarct dementia, Reduced ability to organize thoughts or actions
Decline in ability to analyze a situation, develop an
(3) vascular dementia due to a strategic single infarct,
effective plan, and communicate plan to others
(4) vascular dementia due to lacunar lesions, Difficulty deciding what to do next
(5) vascular dementia due to hemorrhagic lesions, Problems with memory
(6) Binswanger disease, Restlessness and agitation
(7) subcortical vascular dementia, and Unsteady gait
(8) mixed dementia (combination of AD and vascular Sudden or frequent urge to urinate, or inability to
dementia). control passing urine
Wandering at night
Depression

<
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Registry's
d, Registry) .. 65 yo, male, Dementia Vascular

1807 hospitalized stroke pts in Indonesia 79% diagnosed as stroke < 60 yr

old.SuspVaD566pts(32K).

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Alzheimer's Disease New Criteria for the AD Spectrum

Alzheimer's Disease (AD) is a neurodegenera- 3 clinical phases

tive disorder characterized clinically by - Pre-clinirJal
progressive decline in memory cognition and - Mild cognitive impairment
function, and pathologically by neuritic - Dementia
plaques (IMP), neurofibrillary tangles (NFT),
amyloid angiopathy (CAA), and neuronal and
Separate clinical and pathophysiology
synapse loss.
Use of biomarkers to link clinical syndrome to
pathophsiology

Alzheimer's occurs on a continuum of severity from No

> Mild -^Marked impairment
> The preclinical stage of Alzheimer's disease (AD) has been postulated to be a long
asymptomatic period during which the pathophysiological process is progressing
0nset
1i of end-stage AD Clinical diagnosis
> Preclinical AP subjects have been defined as individuals who have evidence of 100 of MCI* of AD
early AD pathological changes but do not meet clinical criteria for MCI or
dementia1
80-
Asymptomatic jPre-dementia / Dementia
60- phase phase J phase

40-

20. Degree o f cognitive L ^ ^

imHirm"nt -*""!
0-
40 50 60 70 80 Age (years)
*
Estimated start of amyloid deposition

1. Sperling etal.. Alzheimers Dement 2011; 7 (3): 280-292 MCI = mild cognitive impairment
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namic biomarkers of the Alzheimer's

pathological cascade
'' o_____________________|
Tsts-rrwditat^ neuronal Injury end
Brain structure
Memory
Clnka] function

dirsksl dtse.se stsoe

Beta-amyloid (AfJ) is identified by CSF AB^ or PET amyloid Imaging

Tau-mediatsd neuronal injury and dysfunction is identified by CSF tau or fluorodeoxyglucose-PET
Brain structure is measured by use of structural MRI

Jack et l l . Lancet Neurol 2010; 9 (1): 119-128

Current approaches diagnose Alzheimer's when

dementia is present
Risk factor AD

Memory impairment Age

Genetic influences
Impairment in one other domain (aphasia, Down Syndrome
agnosia, apraxia, executive dysfunction) Apolipoprotein E status
Occupational and social dysfunction Female gender
Lack of education
Gradually progressive Head trauma
Not due to another specific cause (other Life style and heart health: Lack of exercise, Obesity,
Smoking, High blood pressure. High blood cholesterol,
dementia, delirium, depression, etc) poorly controlled type 2 diabetes, a diet lacking infruits
and vegetables.

Diagnostic and Statistical Manual of Mental Disorders, 1990

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Genetic AD The pathological cascade in AD

APP gene Unknown
mutations Risk factors: aetiologies
Chromosome Gene %of AD Age at onset Ageing and sex (F>M)
Severe head injury
Altered cerebral perfusion Tau
21 !
APP <1 <, <dil ApoE s4 genotype mutations
Environmental toxins?
14 PS-1 S 1-5 30-60
Abnormal tau
- PS-2> 50-65 phosphorylation
'* Neurofibrillary-I-^
plaque^ ^ftangli
: ;19 ' APOE 50-60 . :60+
Neuronal damage/death

MRI demonstrates brain atrophy in Alzheimer's

Dementia Rha r m aeo I ogica I treat me nt
Acethylcholineesterase (AChE) inhibitors
- Donepezil
- Galantamine
- Rivastigmine
Glutamanergic (NMDA receptor) inhibitor
kHippocampus atrophy
bilateral. - Memantine
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fnes for prescribing cholinesterase inhibitors

Therapy: Prescription only for patients-
Futfjlling criteria for probable AD
Duration of illness being more than 6 months
MMSE score more than 10 (i.K, Mild or moderately severe dementia)
Cholinesterase Inhibitors.
Tacrine : 80 to 160 mg/d
* Donepezil : 5 and 10 mg/d ree phase evaluation of response-
: 6 to 12 mg/d Early (2 weeks) for assessing tolerance and side effects.
Rivastigmine
Later (3 months) for cognitive state,
Galantamine : 20 to 50 mg/d
Continued (6 months) for disease state

NMDA antagonist.
Stop treatment-
Memantine: 5 to 20 mg/d
a) If early evaluation shows poor tolerance or compliance
If deterioration continues at pre-treatmenl rate after 3-6 months of
treatment
If even after reaching maintenance dose accelerating deterioration
continues

KblogicaI treatments EFNS-ENS guidelines 2012

Behavioral therapy The caring family members of people suffering
Memory training from dementia are exposed to a great number of
physical, mental and social burdens, and
Relaxation training (progressive muscle restrictions, putting themselves at risk of falling ill
relaxation) (Good Practice Point).
Music therapy Caring family members need adequate forms of
Art therapy relief to be able to care for the family member at
Pet therapy home for as long as possible, and with the best
possible physical and psychological status (Good
Light therapy Practice Point)
European Journal of Neurology 2012,19:1159-1179

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Clinical Diagnosis of Dementia

Evaluation of dementia:
Clinical history
Cognitive assessment
Functional assessment
Physical and neurological exams
Neuro imaging:
CTorMRI
Screen for depression
Laboratory test

Clinical Diagnosis
Risk Factors
Alzheimer's vs. Vascular Dementia
___________ !______6K

Advancing age . . + :
Feature Alzheimer's Vascular Dementia
Hypertension :'l'-.:'+ ' .."+
Onset Gradual '":".. Sudden or gradual Smoking - ...,t,... +
CHD ' +
Profession Constant insidious Slow/step wise

Focal signs Usually absent

Diabetes -: . +
Present '

Memory Early and severe Mildly affected apoE4'Y + +

Executive function Late Early and severe Dyslipidemia.:': + ' :'-:+''-:]:

. * "- -'
Neuroimaging Normal, atrophy Parenchymal vascular. ;:
Inc. Homocysteine :.,/ + . +/"
injury

Obesity. | +/-
O'Brien Am J Geriatr Psych 2006; 14:724

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CSF Biomarker
Lower CSF levels of Ap 42 in AD may represent increased
incorporation of the CSF AP 42 into amyloid plaques. The
concentration of CSF Ap40 is generally unchanged in AD vs.
controls. Initial studies have demonstrated that CSF Ap 42 levels can
distinguish AD individuals from controls with moderate sensitivities
(78- 92%) and specificities (81-83%).
CSF tau has been shown to be elevated in patients with AD and can
distinguish AD patients from controls with a sensitivity of 80-97%
and a specificity of 86-95%.
Combining Ap and tau have been reported to discriminate AD from
controls with up to 90% sensitivity and 80% specificity in research
settings. In a community-based sample, combined analysis of AP 1-
42 and tau yielded 94% sensitivity for detecting probable AD, 88%
for possible AD, and 75% for mild cognitive impairment.
Panduan Nasional Praktek Klinik
Diagnosis dan Penatalaksanaan Dementia
(PERDOSSI 2015)
Inhibitor Kolinesterase dapat diberikan pada
pasien-pasien dengan demensia vaskular dengan
pengawasan klinisi. Grade A
Inhibitor kolinesterase (donepezil, rivastigrnin
dan galantamin) bermanfaat dalam memperbaiki
fungsi kognisi pasien AD ringan - sedang .
Grade A
Donepezil dan memantin cukup efektif dalam
memperbaiki fungsi kognisi pasien dengan AD
sedang - berat. Grade A
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EFNS-ENS guidelines 2012
Structural imaging should be used in the evaluation of every patient
affected by dementia (Level A recommendation).
CT and standard MRI are used to exclude secondary causes for dementia
such as tumor and inflammatory disease, including abscess or normal-
pressure hydrocephalus (Level A recommendation).
At the current state of knowledge, demonstration of cerebrovascular
disease on imaging is used to support the diagnosis (Good Practice Point)
EEG can also be supportive for the differential diagnosis of the
degenerative dementias. EEG with only dlf- fuse abnormalities suggests
AD, and EEG with both diffuse and focal changes suggests DLB, VaD or AD
[130] (class III evidence)
No studies have addressed the value of genetic counselling for patients
with dementia or their families when autosomal-dominant disease is
suspected. Because the genetics of dementing illnesses is a very young
field, expertise In genetic counselling for the dementias of the elderly is
likely to be found only in specialized dementia research centres (Good
Practice Point)
European Journal of Neurology 2012,19:1159-1179
Panduan Nasional Praktek Klinik
Diagnosis dan Penatalaksanaan Dementia
(PERDOSSI 2015)
Gaya hidup sehat meliputi melakukan olah raga
teratur, konsumsi alcohol secukupnya, stop merokok,
mengkonsumsi banyak buah, sayur, kacang-kacagan,
minyak zaitun (misal: DASH - dietary Approach to
Stop hypertension). Direkomendasikan sebagai
pencegahan primer demensia . Grade A level 1+
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MMSE cases
USIA PENOIDIKAN MMSE
Summary
Pria79th' > 1 8 t h ; .. MMSE.': 19/30"; VCI; tiga bula'nRj:
In older persons presenting with dementia the predominant
kemudian.;i
MMSE :25/30, VCI differential diagnosis is that of Alzheimer's disease.
Alzheimer's disease presents insidiously with prominent episodic
Pria81th, J" 22 t h , ' MMSE: 28/30 , .
memory loss progressing to involve multiple domains.
Moca-lna: 22/30 , AD dan CVD '
Vascular dementia may have a different pattern of cognitive
Prla 50 th 17 th.. impairment with better memory function and more impairment in
MOCA Ina : 25/30, MCI
executive functioning.
Perempuan 23 th 17 th MMSE: 3/30' (Encephalitis)satubulan ;
However, because there is often an overlap between the pathologies
kemudian MMSE: 29/30 of stroke and AD (mixed dementia), differentiation may nonetheless
Pria 48 th .. 17 th . MMSE: 27/30?:, be difficult.
MOCA Ina : 18/30 VCI, errant bulan
kemudian.:
Typically in "pure" AD there are not focal neurological signs or
MMSE:.28/30 ;: radiographic evidence of infarction in areas that could be potentially
MOCA Ina 4 22/30.
-:':; - 4: : related to cognition.

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