An over view of Cognitive disorders (MCI, Dementia) and etiological sub-types of dementia.

1. Dr. Sunil Suthar

2.  Cognition is a term referring to the mental processes
involved in gaining knowledge and comprehension.
 Cognition includes memory, language, orientation,
judgment, performing actions (praxis), and problem
solving etc.
 Cognitive disorders reflect disruption in one or more of
the above domains, and are also frequently complicated
by behavioural symptoms.

3. DSM-IV TRICD-10
 Delirium
 Mild
Neurocognitive
disorders
 Major
Neurocognitive
Disorders
Organic, including
symptomatic, mental
disorders (F00-F09)
 Dementia in AD
 Vascular Dementia
 Dementia in other diseases
classified elsewhere
 Unspecified Dementia
 Organic Amnestic Disorder
 Delirium
 Other mental disorder due
to brain damage
&dysfunction (Mild
Cognitive Disorder
DSM-5
 Delirium
 Dementia
 Amnestic
disorders
 Cognitive
Disorder NOS

4.  Normal cognition
 Subjective cognitive impairment
 Mild cognitive impairment
 Dementia
(Reisberg)

5.  1962 – Karl-Benign senescent forgetfulness
 Malignant senescent forgetfulness
 1986 – NIMH- Age associated memory
impairment
 1994 –IPA- Age associated cognitive decline
 1997 –Canadian study of health - Cognitive
impairment no dementia
 1999 – Peterson – MCI
 2013 – DSM 5 - Mild Neurocognitive Disorder

6.  Age > 50 years
 Subjective complains of memory loss interfering daily
activities
 Memory performance on neuropsychological tests is at
least one SD less than younger adults.
 Intact global intellectual functioning.
 No dementia or any condition that produce cognitive
impairment (stroke, brain trauma).

7.  SCI is characterized by subjective decline in memory and
functioning but does not meet the clinical definition of
MCI, in which subtle changes may become visible to
observers and cognitive impairment is elicited with testing.
 The study found that healthy subjects with SCI who were
otherwise cognitively normal were 4.5 times more likely to
develop MCI or dementia within about 7 years than
healthy subjects without SCI.

8.  Mild cognitive impairment (MCI) is a syndrome of
cognitive decline that exceeds normal age-associated
changes, but is less than that seen in dementia.
 MCI appears to be a transitional state to Alzheimer’s
disease and other forms of dementia.

9.  Dementia refers to a spectrum of brain disorders all of
which involve cognitive impairment but vary widely in
terms of cause, course and prognosis.
 Progressive loss of cognitive/intellectual functions.
 Without impairment of consciousness.

10.  Dementia is a syndrome due to disease of the
brain, usually of a chronic or progressive nature.
 There is disturbance of multiple higher cortical
functions, including memory, thinking,
orientation, comprehension, calculation, learning
capacity, language, and judgement.
 Dementia produces an appreciable decline in
intellectual functioning, and usually some
interference with personal activities of daily
living, such as washing, dressing, eating, personal
hygiene, excretory and toilet activities.

11. DSM-IV TRICD-10
 Significant cognitive
decline from a
previous level of
performance in one
or more cognitive
domains-
1. complex attention,
2. executive function,
3. Learning & memory,
4. language,
5. perceptual-motor
6. social cognition
 Interfere with
independence in
everyday activities
 Ex- Delirium,
Depression, Schiz
etc.
 Decline in memory
 Decline in other
cognitive abilities
 Preserved awareness
of the environment
 Decline in emotional
control or
motivation, or a
change in social
behaviour
 Should have been
present for at least
six months
DSM-5
 Memory
impairment
 One or more of
the following
cognitive
disturbance
1. Aphasia
2. Apraxia
3. Agnosia
4. Executive
dysfunction
 Significant
impairment in
functioning
 Ex- delirium,
schiz, depression
etc.

12.  Prevalence of MCI – 15%
 Prevalence of Dementia – 5 to 7%
 Prevalence of Dementia in India-
◦ Rural area – 0.6 to 3.5%
◦ Urban area – 0.9 to 4.8%

13.  The Dementia India report, 2010 – 3.7 million
Indians were suffering from Dementia. Burden of
Cost for dementia care- 14,700 Crore rupees.
 One of main cause of disability – 12% YLD &
1%YLL
 Impact on caregivers

14.  History - important to interview family
 Physical and Neurologic examination
 Mental status
ABC
 ( A- activity of daily living, B – Behavior, C –Cognition)

15.  Age: 60-70 years
 Gender: female
 Prior stroke
 Hardening of the
arteries
 Heart disease
 High blood pressure
 Diabetes
 Diet
• Cholesterol problems
• Atrial fibrillation
• Smoking
• Low Education
• Family history

16.  Neurodegenerative Diseases
◦ Alzheimer’s disease
◦ Parkinson’s disease
◦ Diffuse Lewy body disease
◦ Progressive supranuclear palsy
◦ Multisystem atrophy
◦ Huntington’s disease
◦ Frontotemporal dementias – e.g. Pick’s disease

17. Type of Dementia % in total Cases
Alzheimer’s Dementia 50-55
Vascular Dementia 30-35
Lewy body Dementia 5-7
Frontotemporal Dementia 3-5
Other Dementias 10-15

18.  Structural Disease or Trauma
◦ Normal pressure hydrocephalus
◦ Neoplasms
◦ Dementia pugilistica
 Vascular Disease
◦ Vascular dementia
◦ Vasculitis
 Heredometabolic Disease
◦ Wilson’s disease
◦ Other late-onset lysosomal storage diseases

19.  Demyelinating or Demyelinating Disease
◦ Multiple sclerosis
 Infectious Disease
◦ Human immunodeficiency virus, type 1
◦ Tertiary syphilis
◦ Creutzfeldt-Jakob disease
◦ Progressive multifocal leukoencephalopathy
◦ Whipple’s disease
◦ Chronic meningitis – e.g. Cryptococcal

20.  Nutritional deficiency:
◦ Vitamin B12 deficiency, Folate deficiency, thiamine
deficiency.
 Organ failure:
◦ Uremic and hepatic encephalopathy
 Endocrine disease:
◦ Diabetes mellitus, hyper/ hypo thyroidism, Cushing's
syndrome etc

21. D = Drugs, Delirium
E = Emotions (depression)&
Endocrine Disease
M=Metabolic Disturbances
E = Eye & Ear Impairments
N =Nutritional Disorders
T = Tumors, Toxicity, Trauma to Head
I = Infectious Disorders
A= Alcohol, Arteriosclerosis
•Alzheimer’s Dementia
•Lewy Body Dementia
•Pick’s Disease
(Frontotemporal
Dementia)
•Parkinson’s
•Heady Injury
•Huntington’s Disease
•Creutzfeldt- Jacob
Disease

22. S.N Feature Cortical versus subcortical
1 Memory C> SC
2 Cognition Aphasia, apraxia and agnosia more common in C, slowed
cognitive processing and disruption in arousal and
attention more common in SC
3 Motor
behaviour
SC>C
4 Motivation Apathy common in both but SC>C
5 Mood Depression common in both but SC>C
6 Pathology Primary changes to neocortex and hippocampus; primary
changes to deep structures like thalamus, basal ganglia, etc
7 Language No aphasia in SC, early aphasia in C
8 Speech Dysarthric in SC, normal in C (late deterioration)
9 Coordination SC>C

23.  Blood sugar
 Complete Blood Count,
 Serum Urea, Creatinine, Electrolytes
 Thyroid function tests
 Serum B 12 & Folate
 Electrocardiogram
 Chest X-ray
 CT Scan of head/ MRI head
 Lumber Puncture (if suspicion of infectious etiology)
 Tests for syphilis, HIV
 Drug screen if appropriate
 Brain biopsy (for confirmatory diagnosis).

24.  Changes in personality
 Delusions and hallucinations
 Mood
 Catastrophic reaction
 Sundowning: drowsiness, confusion, ataxia, falls.

25.  Wandering
 Change in eating habits
 Altered sleep
 Incontinence

26.  Delirium
 Depression
 Schizophrenia
 Normal ageing
 Mental retardation

27. S.N Pseudodementia Dementia
1 Informant aware of memory disturbance
and can date the onset accurately
Onset is insidious and informant usually can
not date onset.
2 Patient complains enthusiastically about
the memory loss
Unlikely
3 Questions about cognitive functions lead
to DON’T KNOW RESPONSE
accompanied by irritation
Try their best but are incorrect
4 History is usually short and often there is
a previous history of depressive episode
History is long and depressive episode may
or may not be present
5 Depressed patients perform better on
memory tests.
Don’t perform well.
6 Memory complains are accompanied by
insomnia, diurnal variation etc.
May or may not be present

28. Feature Dementia Delirium
Onset Slow Rapid
Duration Months to years Hours to week
Attention Preserved Fluctuates
Memory Impaired Impaired recent and
immediate
Speech Word finding difficulty Incoherent
Sleep & wake cycle Fragmented sleep Disrupted sleep, day night
reversal
Thoughts Impoverished Disorganized
Awareness Unchanged Reduced
Alertness Usually normal Hypervigilant or reduced
vigilance

29.  Alzheimer’s disease (AD) is the most common
form of dementia, representing approximately 60-
70% of all cases.
 In 1907, Alois Alzheimer first described the
condition that later assumed his name.
 Alzheimer’s disease is a cortical dementia
characterized by a slow, progressive loss of
cognitive functions.
 AD is the fourth leading cause of death in USA.
No Indian data regarding it.

30.  Characterized by:
◦ Progressive loss of cortical neurons
◦ Formation of amyloid plaques (beta-amyloid is major
component)
◦ Intraneuronal neurofibrillary tangles (hyperphosphorylated tau
proteins is major constituent)

31.  AD is characterized by generalized cerebral cortical
atrophy with widespread cortical neuritic (or senile)
plaques (NPs) and neurofibrillary tangles (NFTs).
 Following mechanisms have been attributed for the
development of Alzheimer’s dementia
◦ Amyloid cascade theory
◦ Neuronal loss
◦ Cholinergic hypothesis
◦ Excitotoxicity
◦ Genetic factors

32.  1. Memory loss that affects job skills
 2. Difficulty performing familiar tasks
 3. Problems with language
 4. Disorientation to time and place
 5. Poor or decreased judgment
 6. Problems with abstract thinking
 7. Misplacing things
 8. Changes in mood or behavior
 9. Changes in personality
 10. Loss of initiative
(Alzheimer’s Association.)

33.  Vascular dementia is the second most common
cause of dementia after Alzheimer's disease.
 Cerebrovascular disease is the second most
common cause of dementia and may be partially
responsible for as much as 30 percent of cases.
 Prevalence rates range from approximately 1.5
percent in people aged 70 to 75 years of age to
approximately 15 percent in people older than 80
years of age.

34.  10% to 20% of elderly patients with dementia have
MRI or CT evidence of focal stroke with focal signs
on neuro exam.
 Dementia begins with stroke and progression step-
wise, suggesting recurrent vascular events
 Develop: early incontinence, gait disturbance, and
flattening of affect
 Treat risk factors for vascular disease.

35.  Hypertension
 Arrhythmia
 Diabetes mellitus
 Vasculitis
 Pulmonary disease
 Substance abuse
 Hyperlipidemia
 Low level of B12 & Folate associated with
increased homocysteine levels- risk of stroke

36. 2 points
1. Abrupt onset
2. Fluctuating course
3. h/o strokes
4. Focal neurological
symptoms
5. Focal neurological
signs
1 point
1. Stepwise deterioration
2. Nocturnal confusion
3. Relative preservation of
personality
4. Depression
5. Somatic complains
6. Emotional incontinence
7. h/o hypertension
8. Associated atherosclerosis
Total score < 4= Alzheimer’s disease
Total score > 7= Vascular dementia

37.  CT scan in multi-infarct
dementia. The ventricles
are normal in size, but there
are patchy radiolucencies
throughout the white
matter. These indicate the
presence of demyelinated
patches, which result from
multiple small infarcts in
the brain.

38. Characteristics Alzheimer’s Disease Vascular Dementia
Sex Women Men
Age Generally over age 75 years Generally over age 60 years
Onset & progression Gradually progressive Stuttering or episodic, with
stepwise deterioration
History of hypertension Less common Common
History of
stroke(s),transient ischemic
attack(s),or other focal
neurological symptoms
Less common Common
Hypertension Less common Common
Focal neurological signs Uncommon Common
Emotional lability Less common More common
Cognitive deficits Uniform patchy

39.  It is a dementia associated with degenerative atrophy of frontal and
temporal lobes.
 Frontotemporal dementia, also known as frontotemporal
degeneration, includes Pick's disease, primary progressive aphasia
and semantic dementia.
 Often begins with marked behavioral disturbances, unlike AD
 Classic form – Pick’s disease
 Patients frequently hot-tempered and socially disinhibited
 Illness progresses for years, like AD
 No treatment is available for it and there is inevitable decline.
 About 50% of patients have family history.

40.  An uncommon type of cortical dementia.
 Frontotemporal dementias have been estimated to account
for 5 and 20 percent of degenerative dementias.
 It is clinically similar to Alzheimer’s in the late stages.
 Early, extravagant personality changes & stereotyped
language output (repetitive joke telling) may help in
differentiating it from AD.

41. Features Pick’s disease AD
Personality change Early Late
Amnesia Late Early
Language disturbances Early Late
Stereotypes Early Mid or late
Apraxia, agnosia, alexia Late Variable
Kluver-Bucy syndrome Early Late
Visuospatial disorientation Rare Common
Age of risk Mean 50, up to 80yrs Risk increases with age
CT Scan Fronto-Temporal atrophy Widespread atrophy
Gross Pathology Anterior hemi. Atrophy, Posterior hemispheric
atrophy,
Histopathology pick’s body Neurofibrillary tangle
Length of illness 2-11 yrs 5-25 yrs

42. ◦ Rapid onset of dementia, transmissible: prion protein
◦ Onset between 40 and 75 years
◦ The disease is usually progressive with 50% of patients
dying within 6-9 months.
◦ Spongiform degeneration and gliosis in cortex
◦ 90% of patients have myoclonus vs. 10% in AD
◦ Progressive dementia and change in personality over weeks
to months
◦ EEG – diffuse slowing and periodic triphasic sharp waves
or spikes
◦ CSF – test for characteristic amino acid 14-3-3 sequence
◦ PrP in tonsils- Suggestive of CJD
◦ MRI- Pulvinar sign in Posterior thalamus

43.  Huntington's disease is classically associated with the development of
dementia.
 Sub-cortical type of dementia, characterized by more motor
abnormalities and fewer language abnormalities than in the cortical
type of dementia.
 The dementia of Huntington's disease exhibits psychomotor slowing
and difficulty with complex tasks, but memory, language, and insight
remain relatively intact in the early and middle stages of the illness.

44.  As the disease progresses, the dementia becomes
complete; the features distinguishing it from
dementia of the Alzheimer's type are the high
incidence of depression and psychosis, in addition
to the classic choreo-athetoid movement disorder.
 Usually have family history.
 DNA repeat expansion: HD mutation through
PCR to measure the number of CAG repeats in
the HD gene.

45.  Encephalopathy in HIV infection is associated with dementia
and is termed acquired immune deficiency syndrome (AIDS)
dementia complex, or HIV dementia.
 About 14% of pts with HIV develop dementia.
 The AIDS Task Force criteria for AIDS dementia complex
require laboratory evidence for systemic HIV, at least two
cognitive deficits, and the presence of motor abnormalities or
personality changes. Personality changes may be manifested
by apathy, emotional lability, or behavioural disinhibition.
 Treat with antiretroviral – may slow dementia

46.  It is a disease of basal ganglion.
 Dementia is present in about 35% - 55% of patients with
Parkinson’s disease.
 Dementia occurs usually late in the disease.
 It causes the dementia of subcortical type.
 Lewy bodies may accompany the neuronal loss in involved
nuclei.
 Depression should be ruled out while assessing the patient for
cognitive deficits.
 The appearance of a single cognitive symptom does not mean
that dementia will develop.
 Cognitive symptoms in PD usually appear after physical
symptoms.

47.  Lewy bodies
◦ pathologic inclusions hallmark of Parkinson’s disease when
restricted to brain stem
 Patients have clinical parkinsonism with early and
prominent dementia
 Lewy bodies found in brain stem, limbic system, and
cortex
 Visual hallucinations and cognitive fluctuations
common
 Patients sensitive to adverse effects of neuroleptics.

48. The patient must have sufficient cognitive decline to interfere with social
or occupational functioning. Early in the illness, memory symptoms may
not be as prominent as attention, frontosubcortical skills, and
visuospatial ability. Probable DLB requires two or more core symptoms,
whereas possible DLB only requires one core symptom.
Core features
Fluctuating levels of attention and alertness
Recurrent visual hallucinations
Parkinsonian features (cogwheeling, bradykinesia, and resting tremor)
Supporting features
Repeated falls
Syncope
Sensitivity to neuroleptics
Systematized delusions
Hallucinations in other modalities (e.g. auditory, tactile)

49.  Triad
1. Dementia: typically subcortical
2. Gait instability
3. Urinary incontinence
 Walk with “feet stuck to floor”
 Symptoms progress over weeks to months
 CT shows ventricular enlargement out of
proportion to cortical atrophy

50.  Most important test – therapeutic LP
1. Remove large amount of CSF
2. Examine gait and cognitive function
 Ventriculoperitoneal shunt may correct if:
◦ Patients improve within minutes to hours of removal of 30
to 40 mL of spinal fluid
◦ Trauma or subarachnoid hemorrhage
 Cause is derangement of CSF hydrodynamics