This document discusses the classification and pathological features of various types of dementia. It describes how dementia can be classified based on the pathological proteins involved, such as amyloid/tau in Alzheimer's disease or alpha-synuclein in dementia with Lewy bodies. It also discusses primary degenerative dementias that primarily affect the cerebral cortex, as well as primary degenerative dementias that involve other brain areas. Secondary and non-degenerative dementias are also outlined. The clinical features and distinguishing characteristics of different types of dementia like Alzheimer's disease, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia are summarized.

1. CLASSIFICATION
OF DEMENTIA
Prof.(Dr) O P Singh

2. BASED ON PATHOLOGICAL FEATURES
Pathology Disorders
Amyloid/Tau Alzheimer’s disease
Alpha-Synuclein Dementia with Lewy Bodies
Parkinson’s Dementia
Multisystem Atrophy
Tau Pathology Frontotemporal Dementia
Progressive Supranulear Palsy
Corticobasilar Degeneration
Trinucleotide repeat Huntington’s Disease
Spinocerebellar Ataxia
Toxic/Metabolic Wilson’s Disease
Hallervorden-Spatz Disease
Prion related dementias Creutzfeldt-Jakob Disease
Gerstmann-Straussler Disease
Fatal Familial Insomnia

3. PRIMARY DEGENERATIVE DEMENTIA
• Dementia ‘Pure’ – Neurodegenerative disorder primarily involving cerebral cortex.
Alzheimer’s disease
FTD
 Primary Progressive Aphasia
 Semantic Dementia
Posterior cortical atrophy –
 Primary Progressive Apraxia
 Primary Progressive visual-spatial Impairment

4. PRIMARY DEGENERATIVE DEMENTIA
• Dementia ‘Plus’ – Neurodegenerative disorders involving additional brain areas
such as basal ganglia or other subcortical structures.
DLB
Parkinson’s disease dementia
Corticobasal degeneration
Huntington’s disease
Progressive Supranuclear Palsy

5. SECONDARY/NON DEGENERATIVE DEMENTIAS
• Vascular – multi infarct dementia, strategic single infarct dementia
• Infectious – HIV, Neurosyphilis, Whipple’s disease,
• Demyelinating – Multiple Sclerosis
• Endocrine – Hypothyroidism, Cushing’s syndrome, Adrenal insufficiency
• Vitamin deficiency – B12, B1, folate, niacin
• Toxicities – heavy metal, Wernicke-Korsakoff syndrome, Marchiafava-Bignami
• Others – NPH, Dementia syndrome of Depression.

6. CORTICAL VS SUBCORTICAL DEMENTIA

7. NOT ALL MEMORY DISTURBANCE IS ALZHEIMER’S DISEASE
Dementia Clinical features
Alzheimer’s disease Memory Deficit
Aphasia, Apraxia, Agnosia
DLB Memory Deficit
Fluctuating attention,
Extrapyramidal signs,
Psychosis
FTD Memory Deficit
Speech/ Language Disorders, Disinhibition,
Hyperorality
Huntington’s disease Memory Deficit
Executive Dysfunction,
Chorea
Creutzfeldt-Jakob Disease Memory deficit
Ataxia, Myoclonus,
Language Disturbances.

8. COGNITIVE DECLINE
Depression
Other psych
Delirium Drug Induced Dementias
Alzheimer
Vascular
Lewy body / PD
Frontotemporal
Alcohol
Recreational
Prescriptions !
Many causes!
Alone, or
With dementia
Trauma, Tumor,
MS, HIV, Syphilis,
NPH,Vasculitis, CJD
Hepatic, Renal, or
Thyroid disease
Deficiency (B12)
Toxins, OSA
DIFFERENTIALS OF COGNITIVE DECLINE

9. VASCULAR DEMENTIA
• Features
 Abrupt onset and/or stepwise decline
 Fluctuating course
 H/o stroke
 Focal neurologic symptoms or signs
• Usually bilateral infarcts
• Often associated with executive
dysfunction, gait disorder, apathy,
incontinence

10. DEMENTIA WITH LEWY BODY
• Relatively earlier occipital and basal
ganglia degeneration
• Similar to Parkinson disease dementia
• α-synuclein aggregates into Lewy bodies
• Concurrent AD pathology is common
• REM sleep disorder (dream enactment)
• Neuroleptic sensitivity

11. FRONTOTEMPORAL DEMENTIA
• Often familial (30-50%)
• Overlap with progressive supranuclear
palsy, ALS, and cortico-basal
degeneration
• Pathologic aggregates of tau or TDP-43
• Behavior and personality change (may
misdiagnosed as a psychiatric
disorder)
• Executive dysfunction
• Progressive non-fluent aphasia

12. PARKINSON’S DISEASE DEMENTIA
• About 50 to 80 percent of Parkinson’s
eventually develop dementia.
• Average duration from a Parkinson’s
diagnosis to the development of dementia is
about 10 years.
• Changes in memory, concentration, and
judgment
• Difficulty interpreting visual information
• Muffled speech
• Rapid eye movement (REM) sleep disorder
• Visual hallucinations, delusions, and
paranoia
• Depression, irritability, anxiety, and sleep
disturbances

13. HUNTINGTON’S DISEASE
• Rare inherited disease
• About 3-7 / 100000 population
• Trinucleotide repeat defect.
• Usual age of onset 30-50 years
• Tetrabenzine can be used for
choreiform movements.

14. CREUTZFELDT JACOB DISEASE
• Rare disorder, affects 1 in one million
• Cause – Accumulation of Prion Proteins
• Age of onset – 50 , Rapidly Progressive, average survival 1 year.
• Early stages – failing memory, behavioral changes, poor coordination,
visual impairment.
• Associated features – Insomnia, depression, or unusual sensations.
• Late stage – Worsened mental deterioration, involuntary or jerky
movements, muscle weakness, blindness, and coma.

15. NORMAL PRESSURE
HYDROCEPHALUS
• Triad of DEMENTIA,
GAIT DISTURBANCES
& URINARY
INCONTINENCE.
• Can be
Primary/Idiopathic
• Secondary causes
include SAH,
Meningitis, Trauma,
Surgery etc.

16. MIXED DEMENTIA
• Overlap of Alzheimer’s disease with other Dementias.
• Distinguished by their underlying pathologies.
ALZHEIMER’S
60-70%
VASCULAR
DEMENTIA
10-20%
DEMENTIA
WITH LEWY
BODY
15-25%

18. NEUROLOGICAL EXAMINATION
• AD does not have motor abnormality until late
• Hemiparesis or focal neurological deficit – MID or SOL
• FTD – axial rigidity, supranuclear gaze palsy or features of ALS
• DLBD – initial parkinsonism features
• NPH - Gait problem, urinary incontinence
• PSP – unexpected fall, axial rigidity, vertical gaze palsy and dysphagia
• CJD – diffuse rigidity, akinetic state and myoclonus
• Dementia with myelopathy or neuropathy – alcohol or other vitamin deficiency or heavy metal intoxication

20. WHEN TO
SUSPECT
BVFTD?
• Personality:-
• Less tactful
• Improper manner, inappropriate touching
• Overt sexual comments
• Disinhibited physical acts or comments,impulsive
• Wandering
• Decreased spontaneity, interest and personal
hygiene.
• Emotion:-
• Blunting of emotion,less sympathy
• Less happiness or sadness

21. • Executive function:-
• Low insight
• Inefficiency in planning and problem solving
• Stimulus bound behaviour—echolalia, utilization (grasping, repeated using of
objects and reading aloud that they see.
• Special preoccupation:-
• Stereotyped behaviour (lip smacking, hand rubbing, clapping, counting aloud,
humming, collecting and hoarding object, counting money)
• Sweet food, cramming, bingeing

22. DLB
Consensus criteria: - 2005, McKeith
• Central feature: - Dementia (early features are impairment in attention.
Executive and visuospatial domains.
• Core features:-
 Fluctuating cognition with pronounced variation in attention and
alertness.
 Recurrent visual hallucination that are well-formed and detailed
 Spontaneous features of parkinsonism
• Suggestive features:-
 REM sleep behaviour disorder
 Severe neuroleptic sensitivity
 Low dopamine transporter uptake in basal ganglia by SPECT/PET
• Probable DL: -2 Core features/ one core + one suggestive features
• Possible DLB feature 1 Core / 1 suggestive feature

23. DLB- BEYOND
CRITERIA
 VH is most specific to DLB by 90% (sensitivity 22% in early
stage).
 Visuospatial impairment is most sensitive by 74%.
 Worse performance in attention, executive and visuospatial
and visuoconstructional spheres.
 74% of DLB and 45 % of AD have VS & VC impairment.
 Intersecting pentagon is very helpful in mild to moderate
dementia (MMSE>13) to differentiate DLB & AD
 In DLB, more involved are digit span, selective and
sustained attention, and fragmented letter identification
than AD.
 Intrusions are more common in DLB.It may be of memory
tasks (elements from one story to another), non-memory
(recitation of month-“England”), fluency and environmental.

24. DISEASES
CAUSING
TRANSIENT
AMNESIA
• TGA
• TBI
• Migraine
• Whiplash
• Seizure
• Hypoglycaemia
• Cerebral ischaemia
• Alcoholic blackout
• ECT
• Drugs eg Diazepam, Scopolamine
• Dissociative disorders

25. SOME D/DS
• Less aware of their memory loss
• Greater tendency to confabulate
• Longer span of retrograde amnesia
Diencephalic damage vs MTL damage
• Motor automatism/ unresponsiveness (CPS)
• Usually less duration(CPS)
• Repetitive queries during amnesia (TGA)
TGA vs CPS

26. DIFFERENTIATION
OF APHASIA WITH
SCHIZOPHRENIA
• Many aphasic patients had spent their life in mental hospitals
• Acute onset
• Word finding problem
• Paraphasic errors
• Associated features - delusions in psychosis and focal signs in
aphasia (Probably most important)

27. COGNITIVE ROLE OF DIFFERENT CORTICAL REGIONS
Dementia can also result from subcortical damage
Speech processing:
Temporal - Inability to comprehend – sometimes confused with deafness, fluent empty speech
Semantic problem – specific naming problems, reliance on jargon or low frequency words
Inferior frontal - Expressive problem – slow effortful language, pared down to essential words
Dyspraxia: parietal and frontal
Difficulty carrying out practical tasks – dressing, washing
Speech. Calculation also left parietal.
Visuoperceptual/spatial processing:
Occipital and parietal
Ignores half of space
(usually left half) e.g.
misses food on plate,
ignores people on left
Difficulty laying the table
Fails to recognise objects
Difficulty navigating surroundings –
bangs into doorframes etc
Executive function: frontal
Behavioural difficulties – aggression, apathy,
disinhibited, fatuous. Difficulty sequencing
tasks e.g. shopping, job. Development of rituals
Change in food preference
Memory and navigation: Medial temporal
Classically cannot recall recent events
Will not retain new information
Difficulty navigating surroundings

28. DEPRESSION
AND DEMENTIA
• Risk of dementia - ↑2 times with H/O Depn
• Recurrences – each recurrence ↑14% risk of dementia
• Late life depression - ↑risk for dementia
• Chronic depression - ↑risk for dementia often vascular

29. SUBTYPES OF
DEPRESSION IN
DEMENTIA
• Emotional reaction to cognitive deficits
• Recurrence of early and midlife major depressive
disorder
• Vascular depression of Alexopoulos
• Neurodegenerative process of AD causing depressive
symptoms

30. DEPRESSION
AND DEMENTIA
• 1/3 of the patients with dementia have depressive symptoms
• Risk of dementia is doubled in geriatric depressive patients
• Relationship between depression and dementia is not due to
vascular pathology
• Antidepressant treatment or physical exercise enhance
neurogenesis
• AAGP Annual
Meeting 2008

31. REASONS
BEHIND THE
ASSOCIATION
• Vascular risk factor – both depression and dementia
• ↑cortisol levels in depression – hippocampal atrophy
• Depression - ↑disequilibrium between Aβ production and
clearence
• Inflammatory process – both depression and dementia
• ↓BDNF found in depression – dementia
• Depression - ↓telomere length

32. DEPRESSION
AND APATHY
• Linguistic problem /difficult to diagnose
Mild to moderate stages
More self pity,rejection sensitivity,
anhenodia.
• Difficult to distinguish with apathy sometimes
• Sadness, feelings of guilt, self-criticism, helplessness and
hopelessness are not found in apathy

33. DEPRESSION
AND APATHY
• Apathy is lack of motivation and lack of emotional
responsiveness and emotional indifference.
• Apathy may be associated with disinhibition
• May be motoric, cognitive, affective
• Not concerned about the problem
• Medial PFC may be region

34. THANK YOU
ACK-PROF MALAY
GHOSHAL