Dr.

TARUN MATHUR
CONSULTANT NEUROLOGIST
DM NEUROLOGY, FINR(SWITZERLAND)
SEVENHILLS HOSPITAL

Ü1
SCOPE

• Historical aspects.
• Epidemiology.
• Classification & Terminology.
• Risk factors & Pathogenesis
• Diagnostic criteria.
• Clinical presentation.
• Neuro-radiology
• Treatment.
INDIAN DATA ÜPlay
the violin, beat
dementia
ÜDec 1, 2012, 01.59 PM IST
• In the next three years, India is
expected to race ahead of the
US to become the country with
the maximum dementia
patients.

• The stats found a mention in the

Dementia India Report 2010
prepared by the Alzheimer's and
Related Disorders Society of India
(ARDSI).
• Projected
changes
between 2006
and 2026 in
number of
people living
with dementia
by State in
INDIA
Prevalence of dementia in India

•Low estimate 1.9% over age 65 (Ferri C

et al Lancet 2005; 366: 2112)

•Higher estimate 2.7% over age 65 (Kalaria

R et al Lancet Neurology 2008; 7:812)
• For the year 2010, an estimated 3.7 million Indian people aged
over 60 had dementia (2.1 million women and 1.5 million men)

• Alzheimer's Disease was the most common type of dementia in

INDIA constituting about 45-50 %, the prevalence of vascular
dementia was found to be 25 % in India as against 5 % in the West.

• While mean age of dementia patients was around 65 years in

India, it was 75 years in the West.

• Hypertension, diabetes, cardiovascular diseases and stroke were

among the chief causes for a higher rate of vascular dementia in
India.
Highest estimate of prevalence:
Kerala India
• Door to door survey
• Screen with MMSE
• Full assessment if < 23

Age 65-69 70-74 75-79 80-84 85-89 90+

% 0.6 2.0 5.2 7.1 11.8 13.3

Shaji S et al Br J Psychiatr
2005; 186: 136
 TYPES OF
DEMENTIA
• Alzheimer’s
• Mixed
• Lewy-body
• Frontotemporal
• Vascular
• Other neurodegenerations (e.g.Huntingdon’s)
• Infections (e.g. HIV,Jakob-Creutzfeld)
TYPES OF DEMENTIA
• Alzheimer’s
• Mixed ► 80% of all dementias
• Lewy-body
• Frontotemporal
• Vascular
• Other neurodegenerations (e.g.Huntingdon’s)
• Infections (e.g. HIV,Jakob-Creutzfeld)
THE CHANGE…….

(A) Pie chart that shows previous representation of the distribution of dementia syndromes.
(B) Newer representation of the overlap and relative distribution of dementia syndromes.
J Stroke Cerebrovasc Dis. 2006 Mar-Apr;15(2):49-56.
Pattern of vascular dementia in India: study of clinical features, imaging, and vascular mechanisms from a
hospital dementia registry.
Alladi S, Kaul S, Meena AK, Somayajula S, Umadevi M, Reddy JM.
Source
Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India

PATTERN IN INDIA

• NINDS-AIREN criteria were used.

TYPE OF VASCULAR DEMENTIA

1.Subcortical dementia (52.4%): most common

2.Cortical-subcortical (26.2%)
3.Strategic infarcts in (14.3%)
4.Cortical dementia (7.1%)
 • However Dr. Emil Kraepelin coined
• Alois Alzheimer, described in 1907 the
the term “Alzheimer’s Disease” in the
case of Auguste Deter, who at the age of
51 had developed an early-onset eighth edition of the Textbook of
dementia with psychotic features. Psychiatry, in which he included a
description of Auguste Deter’s
• On post mortem, he had found plaques, disorder; omitting to mention
tangles and arteriosclerotic changes in Auguste D's arteriosclerotic changes,
her brain. hallucinations, delusions and other
psychiatric symptoms
• He had no intention of announcing a new
disease.

ÜIt has been suggested that Kraepelin was

probably motivated to present his already
famous colleague’s clinical case as a newly
discovered illness in order to increase the
prestige of his department.
 HISTORICAL
ASPECTS
• Otto Binswanger was first to consider vascular
cause of dementia and coined the term “
Encephalitis Subcorticalis Chronica Progressiva
(ESCP).”

• Alois Alzheimer coined terms “Binswanger`s

disease” & “ Arteriosclerotic dementia” and
described white matter changes in dementia.

• In his original paper, Alzheimer

described atherosclerosis,
endothelial proliferation, and
neovascularisation in dementia.
Auguste D.
-First seen by Dr Alzheimer
in 1901 when she was in
her early 50s
-Memory impairment
-Hallucinations
-Executive dysfunction
The Nun Study
 The Nun Study
• Longitudinal study of the Teaching Sisters of Notre
Dame (USA)
• 678 enrolled since 1991 aged 75-102
• Written autobiographies within 2 years of entry
• Annual cognitive testing
• Brain autopsies
• 400 deceased by 2003

Snowdon DA Ann Intern Med 2003;139: 450

The Nun Study: pathology of those
with dementia

Alzheimers alone 43%

Mixed (AD + strokes) 34%
Other types of pathology 20%
Vascular alone 2.5%
PARTS AND
FUNCTIONS

Ü18
 LOBES OF HUMAN BRAIN

Gyri

Sulcus
Ü20
Alzheimer’s disease anatomical
correlates: 3 phases of illness

• Limbic system: memory

• Parietal: spatial organization, function
• Frontal: behaviour
 Risk Factors for Alzheimer’s disease
• Age
• Family history
• Lifestyle
Physical exercise
Mental exercise
Diet
Tobacco
Head injury
• Hypertension
• Elevated serum cholesterol
• Elevated serum homocysteine
 Frontotemporal dementia

•Familial in 50%
•Serotoninergic (vs. cholinergic) deficit
•Memory not a prominent feature until
late
•Often difficult to manage
 Frontal lobe dementia
• Trouble in maintaining normal social and • Language Problems
interpersonal functioning.
• limited speech output
• They may become emotionally aroused very
easily.
• perseveration (a meaningless
persistence of verbal activity), a
• Insensitivity – lack of consideration to others. considerable amount of repetition,
• lack of restraint - stealing or unsocial especially of brief words and
behaviour phrases.
• Obsession
• Often there is jargon and instead of
• Sexual misadventures being able to find the word to
describe an object, the person with
this disease will give a description of
• Kluver Bucy Syndrome
• hypersexuality, gluttony, and an it instead (ie., a "watch" referred to
obsession to touch and seize any objects as "something you tell the time
in the person's field of vision. with").
Overeating may lead to considerable
weight gain. Ü24

• Eventually the person becomes

mute.
 EMOTIONAL LABILITY AND FRONTAL
LOBE
• Orbitofrontal lesions – emotionally labile & affect is out of
proportion to that for the stimulus.
• Emotional incontinence
• Inappropriately humorous about serious subjects.

Ü25
ORBITOFRONTAL SYNDROME

Disinhibition & impulsivity of thought, affection & action:

• Lack of judgment, social tact.

• Irritability
• Inattention, increased motor activity

Ü26
 MANIA AND FRONTAL LOBE

• More often with Right

hemispherical lesions
• Orbitofrontal syndrome –
euphoria, uncontrolled
thinking and behavior and
insomnia

Ü27
Bilateral Frontal lobe lesion
6. Limitation of utilization
1. Pseudodepressed - Apathy, behavior
Abulia, akinetic mutism,
7. Frontal release sign
2. Impulsiveness and irritability a. Snout
3. Inability to sustain attention b. Suck
4. Decomposition of gait c. Palmomental
5. Sphincter disturbance d. Grasp
e. Brow tapping

Ü28
Can we predict who will develop
dementia?
Knowing the following risk factors in middle age a
calculation of future likelihood of dementia:
• Age
• Level of permits education
• Systolic BP
• BMI
• Total serum cholesterol
• Degree of physical activity

Patterson C et al CMAJ 2008; 178:548

 Frontal Lobe History taking
• Personality changes

• Hyperorality

• Distractibility

• Poor motivation

• Inability to adapt to new situations

• Poor problem solving skills Ü30

Frontal release sign

• Grasp reflex • Snout reflex

• Forceful grapping of object on
touching palm or sole • Palmomental
• Sucking reflex
• By touching the lips • Glabellar tap
• Groping reflex
• Involuntary following with
hand/eye of moving object
• Stimulus capture
• Utilization behavior

Ü31
 Trail Making Test

A 5 B
4

6
1 C
2
3 D
7
Various levels of difficulty:
1. “Please connect the letters in alphabetical order as fast as you can.”
2. “Repeat, as in ‘1’ but alternate with numbers in increasing order”
 EXECUTIVE DYSFUNCTION
Visual pattern completion test

Ü33
Ü34
VASCULAR DEMENTIA
A dementia of vascular origin,
including cerebrovascular disease or
cerebrovascular insufficiency.
 Malpighi was affected by stroke involving right side of his body. He got
clear of apoplexy & palsy in about 40 days; however he continued to
suffer “ in his memory and reason and melted into tears on slightest
occasion.”

This was, probably, the first case of Vascular Dementia in literature.

….Hachinski VC et al
 EPIDEMIOLOGY
• Vascular dementia is second most common dementia after the
degenerative dementias and is more common in Asian population.

• The prevalence of VaD, world over ranges from 3% to 21%.

70.00%
60.00%
A: ASIA 50.00%
40.00% AD
30.00% VaD
B: EUROPE 20.00% OTHERS
10.00%
0.00%
C: N. AMERICA A B C D
(J. Neurol. Sci 2002)
• Vascular cognitive impairment (VCI) is a heterogeneous group of cognitive
disorders that share a presumed vascular cause.

• VCI have a specific cognitive profile in which memory is preserved and

executive function impaired. (O’Brien 2003; but not always so)

• Common, costly, and possibly preventable.

• 5% of people over the age of 65 are estimated to have VCI.

• VCI has replaced the term MID (multi-infarct dementia)

• By requiring impairment in activities of daily living for a diagnosis
of dementia, many VaD cases are detected only when the brain
damage has reached a degree where successful treatment was no
longer possible.

• Thus, it has been suggested that a broader category be introduced

to include the whole spectrum of cognitive impairment related to
cerebrovascular disease.

VCI is, therefore, an umbrella term.

VASCULAR COGNITIVE IMPAIRMENT

VCIND
(Vascular VaD
cognitive MIXED
(Vascular
impairme
Dementia (VCI+AD)
nt NO
)
DEMENTI
A)
SUB TYPES OF VCI
VCIND (no dementia) Cognitive impairment at least involvement in
one domain
Unaffected activities of daily living
Do not meet currently accepted criteria for
dementia diagnosis
Most affected individuals have a period of
prolonged plateaus

VaD (Vascular dementia) Dementia

Mild memory impairment

Greater disturbance in executive

functioning

Fluctuating, gradual progressive, and/or

stepwise deteriorating cognition
MIXED VCI/AD Dementia
Major disturbance in memory

Atypical course (e.g. sudden exacerbation,

fluctuating, or with a mild plateaus) but
mimicking that of AD

More rapid cognitive impairment than

those of VCI or AD alone
TYPES OF VASCULAR COGNITIVE IMPAIRMENT
VASCULAR DEMENTIA
DISTRIBUTION

ÜCORTICAL ÜSUBCORTIC ÜSTRATEGIC

INFARCT AL INFARCT INFARCT

DEMENTIA DEMETIA
ETIOLOGYDEMENTIA

ÜLARGE ÜSMALL

VESSEL VESSEL
DEMENTIA DEMENTIA
• The most frequent form of VaD is caused by small-vessel disease
(50%), followed by large-vessel disease (23%), and then both (16%)

CEREBRAL
SMALL VESSEL
DISEASE
 RISK FACTORS

NON MODIFI
MODIFI ABLE
ABLE
• Hypertension
• Gender • Diabetes mellitus
• Age • Ischemic heart disease
• Genetic predisposition
• Peripheral vascular disease
• Ethnicity
• Smoking
• A previous history of stroke.
• Hyper-lipidemia
• The two most important non-modifiable risk factors are male gender and
increasing age.

• Genetic defects include monogenic disorders like CADASIL, hereditary

cerebral hemorrhage with amyloidosis, etc.

• Ethnicity: VaD represents over 50% of dementias in Japan….. However in a

recent study in China the prevalence of dementia subtypes was comparable
with that in Western countries (Zhang et al 2005).

• There is a history of prior stroke in 76% of patients with vascular dementia as

compared with only 5%–7% of people with AD.
• Diabetics are over three times more likely to experience stroke-associated
dementia.

• Heart failure: Cognitive impairment is seen in 26% of patients discharged

from hospital after treatment for heart failure, and it correlates with the
degree of LV dysfunction and systolic BP levels below 130 mm Hg.

• CABG surgery: the reported incidence of early cognitive disturbance ranges

from 33% to 83%; Long term cognitive outcome seems to be more
favourable for off-pump CABG.

• Dyslipidemia: elevated levels of LDL-C and decreased levels of HDL-C are

weak risk factors for VaD.
• T. Pohjasvaara et al. evaluated the effect of different clinical criteria for VaD in a series of
107 patients: Different criteria gave different frequency estimates in dementia
diagnosis.
• Most widely used are the NINDS-AIREN criteria and the most specific of all available
criteria.
DSM IV criteria for Vascular dementia (American Psychiatric Association)

The DSM-IV criteria have good sensitivity,

but low specificity
MODIFIED HACHINSKI SCORE

• A total score 7 or more indicates

Multi-infarct dementia.

• A total score 5-6 indicates Mixed

dementia.

• A total score 4 or less indicates

Alzheimer’s disease.
A. COGNITIVE IMPAIRMENT in VCI

1. Cognitive impairment documented by history taking, clinical manifestations, and

neuropsychological tests.

2. Presence cortical and/or subcortical cognitive impairment, but mainly as frontal

or subcortical impairment.

3. Cognitive impairment at least involvement in one domain (Aphasia, apraxia,

agnosia, executive function), or executive dysfunction/impaired memory plus
additional one cognitive impairment, with “patchy” distribution of cognitive
impairment in the earlier stage.

4. Affected people with/without impaired social abilities and/or ADL;

5. Affected people with/without neuropsychic symptoms or BPSDs (e.g., anxiety,

sleep alteration, depression, apathy, agitation, behavioral abnormality,
etc.).
CORTICAL INFARCT DEMENTIA (Multi infarct
dementia)
• Results from multiple large complete infarcts, usually from large-
vessel occlusions involving cortical (and also sub-cortical) areas.

• Characterized by TIAs or stroke episodes (athero thrombotic,

cardio embolic and infarcts in cortical watershed areas) in close
time relation to the development of dementia.

• Stepwise deterioration is considered a hallmark of MID

Axial CT showing large areas of cortical

and subcortical infarction in the right
hemisphere with associated dilation of
the right ventricle.
 CHARACTERISTIC SUBCORTICAL DEMENTIA CORTICAL DEMENTIA
Primary functional lesion Impaired information Domain-specific deficits
processing (aphasia, apraxia, agnosia)

Speed of cognition Slow Normal

Memory deficit Retrieval (recall aided by cues Encoding/storage (poor

and recognition) recognition memory)
Neuropsychiatric symptoms Apathy, depression Depression less common

Motor abnormalities Dysarthria, extrapyramidal Uncommon, gegenhalten

Pathology Prominent changes in Prominent changes in cortical

striatum and thalamus association areas

Exemplary dementia Progessive supranuclear palsy Alzheimer's disease

(Courtesy Dementia-A review

Ü58
Dr.Kadam)
SUBCORTICAL ISCHEMIC VASCULAR
DEMENTIA
BINSWANGER
LACUNAR
DISEASE
STATE

(Subcortical
(Multiple
arteriosclerotic
lacunar
encephalopath
infarctions)
y – SAE)
Main features are
dementia, a pseudobulbar
state, and a gait disorder,
alone or in combination.
BINSWANGER DISEASE (Subcortical arteriosclerotic encephalopathy
SAE)
• Onset between 50 to 65 years.
• Gradual onset of cognitive difficulties is the first sign of SAE in more than 50 % cases.
• Apathy, slowed thinking are prominent and memory deficits are most prominent for delayed recall,
with relative sparing of recognition memory
• Compared to Lacunar state, SAE is associated with more extensive WMLs and ventricular enlargement
STRATEGIC INFARCT DEMENTIA

• Isolated infarcts in “strategically” localized areas which

can cause cognitive disorders disproportional to their
size.

These include:
• Caudate nucleus
• Medial nucleus of thalamus
• Rest of the basal ganglia (esp. globus pallidus)
• Angular gyrus
• Basal forebrain, etc……
 CEREBRAL HEMORRHAGE RISK FACTORS

Spectrum

• Chronic SDH
• SAH
• ICH
• CAA (Cerebral Amyloid Angiopathy)
HYPOPERFUSION DEMENTIA

• CCF: The cognitive impairment is correlated with the degree of left-

ventricular dysfunction and with systolic blood pressures below 130 mmHg.
(Pullicino et al, 2001).

• Post CABG surgery.

• Post major surgery, particularly hip fracture repair.(esp. patients with

diabetes and hypertension)

• AF: In atrial fibrillation a reduced cardiac output might be responsible for

cerebral hypoperfusion.

• Cardiac arrest
VaD Vs AD
 • STEP 2: Now look for the pattern-
• STEP 1: Exclude all, treatable diseases global atrophy, focal atrophy and for
like subdural hematomas, tumors, vascular disease (i.e. infarcts, white
hydrocephalus, etc. matter lesions, lacunes, microbleeds)
• Vascular Dementia (VaD):
Global atrophy, diffuse white
matter lesions, lacunes and
'strategic infarcts‘

• Alzheimer's disease (AD): medial temporal lobe

atrophy (MTA) and parietal atrophy.

• Frontotemporal Lobar Degeneration (FTLD):

(asymmetric) frontal lobe atrophy and atrophy
of the temporal pole.
 WHEN TO CONSIDER WML SIGNIFICANT??

1. When the white matter

changes occupy at least 25%
of the white matter. Change
less than this is unlikely to
be of clinical significance
(Roman et al)

2. Use the FAZEKAS scale.

Axial FLAIR MRI showing extensive WM change occupying more than

25% of the white matter and consistent with a clinical diagnosis of
subcortical dementia.
1 Multiple punctate lesions

2 Beginning confluency of lesions

(bridging)

3 Large confluent lesions

• SUBDURAL HAEMORRHAGE

• SURGICALLY CURABLE
DEMENTIA!

Ü70
THANK YOU

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