Rohit Kumar Turi Clinical Psychologist

2. Vascular (Multi-infarct) dementia
(MID)
 2nd most common cause.
30%
 ↑ with age, more common
in men
 May coexist with AD
 MRI demonstrates focal
strokes – multiple lacunes
within the subcortical and
even cortical regions

3. Etiology
 VaD caused by atherosclerotic blood vessels to the brain
 Periods of ↓ed blood flow, resulting in repeated
ministrokes in brain
 Ministrokes cause areas of cell death called infarcts.
 If the ministrokes continue, symptoms similar to AD
appear
 The causes & risk factors for VaD r same for vascular dis
in gen:
• high levels of serum cholesterol and triglycerides
• high levels of homocysteine and C-reactive protein
• smoking, etc.
 People with VaD have exposure to higher levels of
fibrinogen (clotting factor) over a long period of time

4. Clinical features
 Cardiovascular Risk Factors
 Cerebral infarction, anoxia/hge due to
arteriosclerotic plaques/thromboembolism.
 Focal neurological signs, multiple risk
factors for cerebrovascular disease
 Relatively sudden onset; recovery
 Cognitively: Step-wise decline
 Decline occurs with each successive stroke
 Cognitive abilities typically involve frontal
symptoms, but can also include other cognitive
difficulties depending on stroke region.

6. Binswanger
Disease

7. Binswanger disease
 Cardinal Features
 Cardiovascular Risk Factors (hypertension)
 Subcortical dementia with executive dysfunction,
memory loss, slowed motor function, ataxia,
incontinence, & loss of verbal fluency. Apathy,
depression, behavioral disturbances & EPS
common.
 Difficulty sustaining “mental set” over time
 Difficulty switching from one task to the other
 Learning and memory is compromised by attention
disturbance, is not a pure anterograde amnesia like AD.
 MRI demonstrates white matter abnormalities and
no focal strokes

8. Time
Binswanger disease
(Subcortical Vascular
Dementia)
Vascular
(Multi Infarct)
Dementia
Time

9. Dementia with Lewy bodies

10. Dementia with Lewy Bodies
 2nd most common dementia
 USA UK 10-25%
 India 6-12%
 China 2-9%
 Japan 0.1%
 Starts in the 6th-7th decade

11. Dementia with Lewy Bodies
 Cardinal features:
- dementia (100%)
- fluctuating cognition (60-80%)
- parkinsonism (80-90%)
- recurrent visual hallucinations (50-75%)
 Supporting features:
– Falls
– Syncope
– Neuroleptic sensitivity
– Systematized delusions
– Hallucinations in other modalities (auditory, tactile)
– REM sleep disorders

12. Dementia with Lewy Bodies

13. Cortical Lewy body

14. Dementia with Lewy Bodies

15. PET in AD,
DLB, FTD

16. Frontotemporal dementia
(Pick’s disease )
Definition: clinicopathologic condition
consisting of deterioration of personality &
cognition assoc. with prominent frontal &
temporal lobe atrophy
 25 times rarer than Alzheimer’s dementia
 Assymetrical frontal or temporal atrophy
 Etiology: unclear; linkage to Ch17,tau
protein mutations
 More common in younger age; onset 35-
75yrs; 20-40 % have family history

17. Frontotemporal dementia
 Gradual change in personality & behavior;
disinhibition, apathy, limited insight, irritable,
inappropriate, impulsive, potentially aggressive
 Perseveration of words, stereotyped behavior,
mental rigidity, inflexibility.
 KB syn: hypersexuality, hyperorality, utilization
beh
 Gradual change in language fun: speech is
impoverished, lack spontaneity. Impairment in
word meaning, reading & writing– perseverative
& echolalic speech—mutism.

18. Pathology
Prominent frontal and temporal lobar
atrophy
Atrophy may be associated with Pick’s
bodies, tauopathy, nonspecific superficial
cortical neuron loss (DLDH)

19. Frontotemporal dementia
Frontal variant Pick Bodies

20. Frontotemporal dementia

21. Cortical
atrophy in
FTD

22.  The marked atrophy of Pick's disease produces
"knife-like" thinning of the gyri in frontal lobes
and temporal lobes.

23. Investigations
Neuropsychology:
Impaired frontal lobe tests in absence of
severe amnesia, aphasia, or visuospatial
deficits
Imaging:
Atrophy or decreased uptake in the frontal or
anterior temporal lobes (bilateral or unilateral)
by MRI, CT, PET, SPECT

24. Normal PET FTD PET

25. FTD

26. FTD Disease Progression

27. FTD subtypes
Progressive
Non-Fluent
Aphasia
(PNFA) Social/Executive
Semantic
Dementia

28. Clinical features distinguish FTD
subgroups
 Dysexecutive
 behavioral disturbances
 Disturbances on tests of executive functioning
 Usually loss of insight into disturbances
 Semantic Dementia & Progressive Non-
Fluent Aphasia
 disruptions of language

31. Degeneration of the basal
ganglia
 Huntington’s disease
 Rare: 5 in 100,000
 abnormal ‘exaggerated movements
 Parkinson's disease
 Common: 1 in 100 over age 65
 General slowing of voluntary movements
 Both diseases involve the basal ganglia,
but in opposite ways

32. Huntington’s Disease
 Huntington’s chorea in 1872
 Prevalence: 0.6 % in white people; less in
black people
 Equally in males and females
 Onset in beyond the age of 30 - 50 years
after the reproductive phase
 Relentless progression of cognitive &
behavioral decline, Leading to death after
5- 20 years

33. Symptoms
 Motor:
 Chorea subtle, excessive, purposeless fidgeting
 Hyperkinetic hypoton, uncontrolled movements,
distally accentuated
like in a confused or embarrassed state
 Dancing like movements, grimacing
 Tongue, speech, swallowing
 Mental:
 Depressed early, later withdrawn, eccentric &
socially isolated
 Schizophrenia-like psychotic symptoms
 Dementia

34. Neuropathology of Huntington’s
Disease
 Caudate nucleus markedly atrophic & gliotic
 frontal lobe pyramidal neuronal loss with
thinning of grey matter
 Polyglutamine nuclear inclusions present
 ↓ GABA in caudate nucleus

35. Aetiology of Huntington’s Disease
 Single gene autosomal dominant disorder with
complete penetrance. New mutations rare
 1 parent bears the gene: 50 % of the children will
fall ill
 1983 HD locus on the short arm of chromosome
4p
 1995 HD a polyglutamine disease: Protein
Huntingtin
 enhanced CAG repeat frequency
 CAG triplet repeat normal: 11 -34
 in HD 37 – 86
 Correlation between repeat frequency & onset of
diesease

36.  Morphology
 A disease of the basal ganglia / striatum
 In HD the spiny I neurons of the striatum
degenerate
 (GABAergic, ENKergic)
 Neurochemistry
 GABAergic projection to the GPe

37. Parkinson’s disease
 Etiology
 Neurons in substantia nigra die
or become impaired (cause
unknown).
 These cells produce the
dopamine.
 Dopamine allows smooth,
coordinated function of the
body’s muscles and movement.
 When approx 80% of the
dopamine producing cells are
damaged, PD symptoms
appear.

38. Parkinson’s disease
 PD symptoms: tremor (shaking),
slowness of movement,
rigidity (stiffness), and
difficulty with balance; may also include
small,cramped handwriting,
stiff facial expression,
shuffling walk, muffled speech and
depression

39. Neurodegeneration
Progressive loss of
dopaminergic
neurons in the
substantia nigra
Formation of Lewy
bodies
Impacts multiple
neurochemical
pathways
dopamine
norepinephrine
serotonin
acetylcholine
GABA
glutamate
Neuronal
Complexity

40. Lewy bodies in Midbrain: Hallmark of
PD

41.  The loss of pigmentation in the substantia nigra
of the midbrain at the left in a patient with
Parkinson's disease is contrasted with a normal
midbrain at the right. Parkinson's disease is
marked clinically by a "pill-rolling" tremor at rest,
mask-like facies, and cogwheel rigidity of limbs,
among other findings.

42.  At the left, normal numbers of neurons in
the subtantia nigra are pigmented. At the
right, there is loss of neurons and loss of
pigmentation with Parkinson's disease.

44. Stage 1
Stage 2
Stage 3
Stag
e 1
Unilateral involvement;
blank faces; affected arm
in semiflexed position
with tremor; patient
leans to unaffected side.
Progression to stage 2 in
~18 months.
Stag
e 2
Bilateral involvement
with early postural
changes; slow, shuffling
gait with decreased
excursion in legs; tremor
on both sides; rigidity. To
stage 3 in ~25 months.
Stag
e 3
Pronounced gait
disturbances and
moderate generalized
disability; postural
instability with tendency
to fall; still independent.
To stage 4 in ~42 months.

45. Stage 4
Stage 5
Stage 4
Significant
disability;
limited
ambulation
with assistance.
Progression to
stage 5 in ~17
months.
Stage 5
Complete
invalidism;
patient
confined to bed
or chair; cannot
stand or walk
with assistance.

46. Parkinson’s Disease:
 Typical Cognitive Profile:
 Retention of Problem Solving Abilities with only
fluctuations in attention and processing speed
 Intact learning and memory, although rapid retrieval
is compromised
 Visuoperceptual abilities may be variable
 Not demented
 Typical Emotional Profile:
 Depressive symptoms reported or may appear
 May appear apathetic or report apathetic symptoms.

47. The picture for Parkinson's
disease is very
encouraging.
DBS for the treatment of
tremor in Parkinson's
disease using a single
implanted electrode or two
implanted electrodes
(bilateral, meaning one on
each side of the brain).
Parkinson’s
Disease:
Treatment

48. Parkinson’s disease
with dementia
 Typically over age 70
 Often has cardiovascular risk factors (hypertension,
diabetes)
 May retain response to Levodopa treatment
 Cognitive Symptoms of PD with:
 Pronounced intellectual decline relative to premorbid
estimates
 Impairment in one other domain:
 Impaired Learning and Memory
 Impaired Language Difficulty
 Impaired Abstract Reasoning

49. Thank
You