Dementias

Study Notes

Sources: Kaplan & Sadock's Synopsis of Psychiatry (12th Ed), Oxford Textbook of Psychiatry, Cummings' Neuropsychiatry and Behavioral Neuroscience

PART 1: OVERVIEW AND DEFINITIONS

1.1 Definition and Conceptual Evolution

Dementia, from Latin demens (without mind), refers to an acquired, persistent impairment in cognition that represents a decline from a previously higher level of functioning and is severe enough to interfere with daily activities.

The term "dementia" has been progressively replaced in formal classification systems:

• DSM-5 (2013): Replaced with Major Neurocognitive Disorder (Major NCD) and Mild Neurocognitive Disorder (Mild NCD)
• ICD-11 (2022): Uses Dementia as the overarching term but categorizes subtypes using neurocognitive disorder framework
• The shift reflects: (a) destigmatization, (b) inclusion of milder presentations, (c) recognition of early intervention windows

1.2 DSM-5 Diagnostic Criteria

Major Neurocognitive Disorder (Major NCD)

A. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains:

• Complex attention
• Executive function
• Learning and memory
• Language
• Perceptual-motor
• Social cognition

B. Cognitive deficits interfere with independence in everyday activities (bills, medications, etc.)

C. Not exclusively during delirium

D. Not better explained by another mental disorder (depression, schizophrenia)

Mild Neurocognitive Disorder (Mild NCD)

Same as above but:

• Modest (not significant) decline
• Deficits do NOT interfere with independence (may require greater effort or compensatory strategies)

1.3 ICD-11 Criteria for Dementia

ICD-11 requires:

1. Decline from a previous level of cognitive functioning
2. Impairment in two or more cognitive domains (memory, executive function, attention, language, visuospatial abilities)
3. Interference with ability to function independently in daily activities
4. Not due to normal ageing, delirium, or another mental/behavioral disorder

ICD-11 Subtypes of Dementia:

• 6D80 Dementia due to Alzheimer disease
• 6D81 Dementia due to cerebrovascular disease
• 6D82 Dementia due to Lewy body disease
• 6D83 Dementia due to frontotemporal lobar degeneration
• 6D84 Dementia due to psychoactive substances
• 6D85 Dementia due to HIV
• 6D86 Dementia due to prion disease
• 6D8Y Other specified dementia

PART 2: EPIDEMIOLOGY

2.1 Global Burden

2.2 India-Specific Epidemiology

10/66 Study (Prince et al.): Landmark study showing dementia prevalence in India at ~3.4% in those 60+. Important because it used population-based sampling and culturally validated tools.

DEMENTIA INDIA REPORT 2010: Published by ARDSI, foundational document for Indian dementia policy. Estimated 3.7 million affected (now revised upward to 5.3 million with updated data).

2.3 Risk Factors

Non-Modifiable

• Age (strongest risk factor)
• Female sex
• Family history / genetics
• Down syndrome (almost universal AD by 40s)

Modifiable (Lancet Commission 2020: 12 modifiable risk factors)

Total potentially modifiable: ~40% of dementia cases

PART 3: MILD COGNITIVE IMPAIRMENT (MCI)

3.1 Definition and Criteria (Petersen 2004, updated)

MCI represents the transitional zone between normal ageing and dementia.

Petersen Criteria for MCI:

1. Subjective cognitive complaint (preferably corroborated by informant)
2. Objective cognitive impairment (>1.5 SD below age/education norms on standardized tests)
3. Preserved general cognitive function
4. Intact or minimally impaired activities of daily living (ADLs)
5. Does not meet criteria for dementia

3.2 Types of MCI

Swipe to compare →

3.3 Conversion Rates

• ~10-15% of MCI cases convert to dementia per year
• After 5 years: ~50% have converted
• 20-30% of MCI revert to normal cognition
• Amnestic MCI has highest conversion risk to AD

3.4 DSM-5 Equivalent

MCI = Mild Neurocognitive Disorder in DSM-5

PART 4: ALZHEIMER'S DISEASE (AD)

4.1 Background

First described by Alois Alzheimer in 1906, patient Auguste Deter, 51-year-old woman with progressive memory loss, delusions, and paranoia. Autopsy revealed senile plaques and neurofibrillary tangles.

Most common cause of dementia worldwide (~60-70% of cases).

4.2 Neuropathology

Gross Pathology

• Cortical atrophy, most prominent in:
• Hippocampus (earliest)
• Entorhinal cortex
• Parietal and temporal association cortices
• Relative sparing of primary motor and sensory cortices (until late)
• Ventricular enlargement (ex vacuo)
• Weight of brain reduced by 10-15%

Microscopic Pathology (Two Hallmarks)

1. Senile Plaques (Amyloid/Neuritic Plaques)

• Extracellular deposits of beta-amyloid (Aβ) peptide
• Derived from cleavage of Amyloid Precursor Protein (APP)
• Dense core surrounded by dystrophic neurites
• Two types:
• Neuritic plaques, with tau-positive dystrophic neurites (pathological)
• Diffuse plaques, less compact, less pathological significance

2. Neurofibrillary Tangles (NFTs)

• Intraneuronal accumulations of hyperphosphorylated tau protein
• Normal tau stabilizes microtubules; in AD, abnormal phosphorylation causes tau to aggregate
• Paired helical filaments (PHFs), characteristic ultrastructure
• Stage distribution: Braak & Braak staging (I-VI)
• Stages I-II: Entorhinal cortex
• Stages III-IV: Hippocampus, limbic system
• Stages V-VI: Neocortex (correlates with clinical dementia)

Additional Pathological Features

• Granulovacuolar degeneration, in hippocampal neurons
• Hirano bodies, eosinophilic intraneuronal inclusions
• Neuronal loss, estimated 50-75% reduction in nucleus basalis of Meynert (cholinergic neurons)
• Synaptic loss, best correlate of cognitive decline
• Amyloid angiopathy, Aβ deposits in vessel walls

4.3 Neurochemistry

4.4 The Amyloid Cascade Hypothesis (Hardy & Selkoe, 1992; revised 2002)

Core Proposition: The central event in AD pathogenesis is the abnormal accumulation of Aβ peptide, which triggers a cascade leading to neurodegeneration.

Sequence:

1. Imbalance between Aβ production and clearance
2. Aβ aggregation → oligomers (most toxic form) → plaques
3. Synaptic dysfunction and neuronal stress
4. Tau hyperphosphorylation and tangle formation
5. Neuroinflammation (microglial activation, astrocytosis)
6. Widespread neuronal death and synaptic loss
7. Clinical dementia

APP Processing:

• Non-amyloidogenic pathway: α-secretase cleaves APP within Aβ region → no Aβ formed
• Amyloidogenic pathway: β-secretase (BACE1) and γ-secretase cleave APP → Aβ40 and Aβ42
• Aβ42 is more amyloidogenic and deposits earlier
• γ-secretase complex includes Presenilin-1 (PSEN1) and Presenilin-2 (PSEN2)

Criticisms of Amyloid Cascade Hypothesis:

• Anti-amyloid therapies (immunotherapy) have had limited clinical success
• Amyloid can be present without clinical dementia
• Tau pathology may correlate better with cognitive symptoms
• "Amyloid accumulation = AD", necessary but may not be sufficient

Current revision: Dual-hit model, Aβ + tau + neuroinflammation all contribute; no single cascade

4.5 Tau Pathology

• Tau is a microtubule-associated protein encoded by MAPT gene (chromosome 17)
• In AD: hyperphosphorylated tau dissociates from microtubules and aggregates intraneuronally
• Braak Staging (I-VI): Hierarchical spread from entorhinal cortex → limbic → neocortex
• Tau PET correlates better with cognitive symptoms than amyloid PET
• Tau spreads via connected neural networks (prion-like propagation hypothesis)

4.6 Genetics of Alzheimer's Disease

APOE Alleles:

• APOE2: Protective
• APOE3: Neutral (most common)
• APOE4: Risk allele, 3-4x risk in heterozygotes; 8-12x in homozygotes
• APOE4 does NOT guarantee AD, it is a risk factor, NOT a deterministic mutation
• APOE4 lowers age of onset by ~7-10 years per allele

4.7 Clinical Stages of Alzheimer's Disease

NIA-AA 2018 Research Framework (Biological Staging: A/T/N)

Preclinical AD: A+ T- or A+ T+, no symptoms

Prodromal AD (MCI): A+ T+, mild symptoms

Dementia due to AD: A+ T+ N+, significant impairment

Clinical Staging (Reisberg Global Deterioration Scale / Clinical Dementia Rating)

Memory Loss Pattern in AD:

• Earliest: Episodic memory (recent events, new learning)
• Then: Semantic memory (names, facts)
• Relatively preserved until late: Remote (autobiographical) memory, procedural memory, implicit memory

4.8 Biomarkers

CSF Biomarkers (Lumbar Puncture)

Sensitivity/Specificity of CSF biomarkers: ~90%/90% for AD vs controls

Neuroimaging Biomarkers

MRI:

• Medial temporal lobe atrophy (MTA), especially hippocampus and entorhinal cortex
• Scheltens score for MTA (0-4): Score ≥2 suggests AD
• White matter changes (incidental)
• Global atrophy pattern: posterior > frontal (unlike FTD)

Amyloid PET (Florbetapir/Flutemetamol/Florbetaben):

• Positive scan: diffuse cortical amyloid accumulation
• Normal = white matter signal only
• Sensitivity ~96%, Specificity ~93% for AD pathology
• FDA-approved; expensive, not widely available in India

FDG-PET:

• Measures glucose metabolism
• AD pattern: temporo-parietal hypometabolism ± posterior cingulate
• Spares primary motor, sensory, visual cortex until late
• Useful for differentiating AD from FTD (frontal hypometabolism in FTD)

Tau PET (Flortaucipir/AV-1451):

• Newer; directly images tau tangles
• Correlates better with cognitive symptoms than amyloid PET
• Shows hierarchical Braak-stage pattern

Blood Biomarkers (Emerging: 2020s)

4.9 Pharmacotherapy for Alzheimer's Disease

Cholinesterase Inhibitors (ChEIs)

Mechanism: Inhibit acetylcholinesterase (and in some cases butyrylcholinesterase) → increase synaptic acetylcholine → compensate for cholinergic deficit

Common Side Effects of ChEIs (cholinomimetic):

• Nausea, vomiting, diarrhea (dose-related)
• Anorexia, weight loss
• Bradycardia (sick sinus, AV block, caution)
• Nightmares (especially donepezil, take in morning)
• Syncope

Clinical Evidence:

• Modest but consistent benefit on cognition (ADAS-Cog +3-4 points vs placebo)
• Benefit on ADLs and global function
• Insufficient evidence for disease modification
• Benefits may be maintained for 1-2 years

Memantine (Ebixa, Namenda)

Mechanism: Uncompetitive, voltage-dependent NMDA receptor antagonist → reduces pathological glutamatergic excitotoxicity; preserves physiological NMDA activity

• Approved for moderate-to-severe AD
• Dose: 5mg OD → 20mg OD (titrated over 4 weeks)
• Can be combined with ChEIs (additive benefit in moderate-severe AD, Tariot et al., 2004)
• Side effects: Dizziness, headache, confusion (usually mild)

Newer Disease-Modifying Agents (Anti-Amyloid Immunotherapy)

Key Points on Anti-Amyloid Therapy:

• Target: early-stage AD (MCI or mild dementia stage)
• Require biomarker confirmation (amyloid PET or CSF)
• Main risk: ARIA (Amyloid-Related Imaging Abnormalities), ARIA-E (edema) and ARIA-H (microhemorrhages), occurs in 20-40% on MRI, symptomatic in 3-10%
• APOE4 homozygotes have highest ARIA risk
• Not yet available in India (cost ~$26,500/year for lecanemab)

Non-Pharmacological Management

• Cognitive stimulation therapy (CST), evidence base comparable to ChEIs
• Physical exercise, reduces progression risk
• Structured activities, reality orientation
• Environmental modifications (safety)
• Music therapy, particularly for agitation

PART 5: VASCULAR DEMENTIA (VaD)

5.1 Overview

Second most common cause of dementia (~15-20% globally; ~30% in India). Results from cerebrovascular disease causing brain injury and cognitive impairment.

5.2 Types of Vascular Dementia

5.3 Hachinski Ischemic Score (HIS)

Used to clinically differentiate VaD from AD (Hachinski et al., 1975).

Interpretation:

• Score ≥7: Vascular dementia
• Score ≤4: Alzheimer's disease
• Score 5-6: Mixed or inconclusive

5.4 Clinical Features of VaD

Onset and Course:

• Typically abrupt onset (post-stroke)
• Stepwise deterioration (each stroke → new step down)
• May plateau between episodes

Cognitive Profile:

• Executive dysfunction prominent (working memory, planning, attention)
• Memory impairment: encoding relatively preserved, but retrieval impaired
• Psychomotor slowing
• Emotional lability, emotional incontinence

Neurological Signs:

• Focal deficits (hemiparesis, dysarthria, dysphagia)
• Gait disturbance (marche a petit pas in subcortical VaD)
• Pseudobulbar palsy
• Urinary incontinence

Neuropsychiatric:

• Depression (very common, post-stroke depression)
• Apathy
• Emotional incontinence (laughter/crying without provocation)

5.5 Neuroimaging in VaD

CT:

• Low-density areas (infarcts)
• Periventricular hypodensities (white matter changes)

MRI:

• Multiple infarcts of varying ages
• White matter hyperintensities (T2/FLAIR), periventricular and deep white matter
• Lacunar infarcts (basal ganglia, thalamus, pons)
• Fazekas scale for white matter changes (0-3)

5.6 Diagnostic Criteria

NINDS-AIREN Criteria (National Institute of Neurological Disorders and Stroke, Association Internationale pour la Recherche et l'Enseignement en Neurosciences):

Probable VaD:

1. Dementia (MMSE and clinical exam)
2. Cerebrovascular disease (focal signs + neuroimaging evidence)
3. Temporal relationship: dementia onset within 3 months of stroke, or abrupt onset/stepwise deterioration

Possible VaD:

• Dementia + focal signs but no neuroimaging
• Dementia + neuroimaging but no clear temporal relationship

5.7 Management of VaD

Primary Prevention:

• Control vascular risk factors: hypertension, diabetes, hyperlipidemia, smoking cessation
• Antiplatelet therapy (aspirin, clopidogrel) for secondary prevention

Symptomatic Treatment:

• ChEIs: modest evidence; donepezil approved in some countries
• Memantine: some evidence
• No established disease-specific treatment

Vascular Risk Factor Management:

• Target BP <130/80 mmHg (JNC guidelines)
• Statin therapy
• HbA1c control

PART 6: DEMENTIA WITH LEWY BODIES (DLB)

6.1 Background

DLB is the second most common neurodegenerative dementia (~15-20%) after AD. Often underdiagnosed. Named after Friederich Heinrich Lewy who described the inclusion bodies in 1912.

6.2 Pathology

Lewy Bodies:

• Intraneuronal inclusions of aggregated alpha-synuclein protein
• Core: dense protein aggregate
• Halo: radiating filaments
• Location: cortical (DLB), brainstem substantia nigra (PD), both (DLB/PDD)

Braak Staging for Lewy Body Disease:

• Stages 1-2: Olfactory bulb, brainstem (no clinical symptoms)
• Stages 3-4: Amygdala, limbic (early symptoms)
• Stages 5-6: Neocortex (dementia)

Neurochemistry:

• Dopamine (nigrostriatal): decreased → parkinsonism
• Acetylcholine: markedly decreased (more than AD) → cognitive symptoms
• Noradrenaline: decreased
• Serotonin: decreased

6.3 Clinical Features: McKeith Criteria (2017)

Essential Feature:

• Dementia, defined as progressive cognitive decline sufficient to interfere with social/occupational function

Core Clinical Features (2 = probable; 1 + biomarker = probable):

Supportive Features:

• Severe sensitivity to antipsychotics (neuroleptic sensitivity)
• Postural instability, falls, syncope
• Autonomic dysfunction (orthostatic hypotension, constipation, urinary incontinence)
• Hypersomnia
• Hyposmia (anosmia)
• Neuropsychiatric symptoms: depression, apathy, anxiety, delusions

Indicative Biomarkers (for probable DLB diagnosis):

6.4 DLB vs PDD: The 1-Year Rule

6.5 Cognitive Profile of DLB

• Early: Visuospatial deficits (constructional apraxia), attentional fluctuations
• Frontal-subcortical pattern: executive dysfunction, processing speed
• Memory: relatively preserved in early stages compared to AD
• Later: global decline

6.6 Management of DLB

Neuroleptic Sensitivity in DLB:

• Occurs in 30-50% of DLB patients exposed to conventional antipsychotics
• Also with risperidone, olanzapine at higher doses
• Can cause rapid functional decline and death
• Mechanism: hypersensitive D2 receptors in the context of cholinergic deficits

Safe Antipsychotics in DLB (relatively):

• Quetiapine (low dose, least dopamine blockade)
• Clozapine (evidence in Parkinson's psychosis; requires CBC monitoring)

Cognitive Symptoms:

• Rivastigmine: approved for DLB and PDD (cholinergic deficit most severe in DLB)
• Donepezil: evidence, not formally approved for DLB in all jurisdictions
• Memantine: modest benefit

Motor Symptoms:

• Levodopa: modest benefit for parkinsonism; may worsen hallucinations
• Avoid dopamine agonists (worsen psychosis)

Psychiatric Symptoms:

• Depression: SSRIs (sertraline, escitalopram)
• Anxiety: SSRIs, low-dose benzodiazepines (caution, oversedation)
• Psychosis: quetiapine, clozapine only

Sleep (RBD):

• Clonazepam 0.25-2mg at bedtime (evidence-based; injury prevention)
• Melatonin 3-12mg (safer in elderly)

PART 7: FRONTOTEMPORAL DEMENTIA (FTD)

7.1 Overview

FTD encompasses a group of neurodegenerative diseases characterized by progressive degeneration of the frontal and/or temporal lobes. It is the THIRD most common neurodegenerative dementia (after AD and DLB) and the MOST common dementia in those under 65.

Prevalence: 10-15% of all dementias; peak incidence ages 45-65

7.2 Clinical Syndromes

PPA = Primary Progressive Aphasia, language-first syndrome

7.3 Behavioral Variant FTD (bvFTD): Rascovsky Criteria (2011)

Required: Neurodegenerative syndrome with progressive behavior/cognition

Possible bvFTD (3 of 6):

Probable bvFTD: Above + neuroimaging showing frontal/anterior temporal atrophy/hypometabolism

Definite bvFTD: Above + histopathological confirmation

7.4 Semantic Dementia (svPPA)

• Anomia: inability to name objects/people
• Empty speech: uses circumlocutions ("the thing you use to...")
• Surface dyslexia and dysgraphia (reads phonetically)
• Preserved syntax and phonology
• Preserved day-to-day memory (episodic) in early stages
• Face recognition impairment (prosopagnosia), right temporal variant
• MRI: asymmetric left anterior temporal lobe atrophy

7.5 Progressive Nonfluent Aphasia (nfvPPA)

• Effortful, halting speech
• Agrammatism (telegraphic speech, dropped function words)
• Phonological errors, apraxia of speech
• Preserved comprehension early
• May progress to mutism
• Often develops overlapping motor neuron disease features
• MRI: left posterior frontal and insular atrophy

7.6 Neuropathology of FTD

Grossly: Knife-blade atrophy of frontal and temporal gyri (most marked in bvFTD and svPPA)

FTLD-Tau (tau-positive inclusions):

• Pick's disease (FTLD-Pick): Argyrophilic Pick bodies (tau-positive intraneuronal inclusions with 3R tau); ballooned neurons (Pick cells)
• Progressive Supranuclear Palsy (PSP): 4R tau; globose tangles; tufted astrocytes
• Corticobasal Degeneration (CBD): 4R tau; astrocytic plaques; neuronal achromasia

FTLD-TDP (TDP-43-positive):

• Most common FTLD pathology (~50%)
• TDP-43 is a nuclear RNA-binding protein; pathological cytoplasmic inclusions
• Associated with MND (Motor Neuron Disease / ALS)

FTLD-FUS (FUS-positive):

• Rare (<10%)

7.7 Genetics of FTD

C9orf72, hexanucleotide repeat expansion (GGGGCC), accounts for ~25% of familial FTD and ~35% of familial ALS. Single most common genetic cause of both FTD and ALS.

7.8 Management of FTD

• No approved disease-modifying therapy
• Behavioral symptoms: SSRIs first-line (sertraline, fluvoxamine) for disinhibition, compulsions, hyperorality
• Atypical antipsychotics: low doses for severe behavioral disturbance
• Avoid ChEIs and memantine, no evidence; may worsen behavioral symptoms (galantamine may worsen hyperorality)
• Speech and language therapy
• Genetic counseling (family members)
• Caregiver education: empathy impairment explanation

PART 8: NORMAL PRESSURE HYDROCEPHALUS (NPH)

8.1 The Hakim-Adams Triad

NPH = Classic triad (described by Adams and Hakim in 1965):

Gait in NPH: Magnetic gait (feet appear glued to floor), wide-based, short steps, difficulty initiating, en bloc turns. Distinguished from Parkinson's: no tremor, no rigidity at initiation.

8.2 Pathophysiology

• Chronic impairment of CSF absorption (arachnoid villi)
• Normal opening CSF pressure on LP (<20 cm H2O), despite enlarged ventricles
• Hydrocephalus compresses periventricular white matter tracts
• Disruption of frontal-subcortical circuits → gait, continence, cognition deficits

8.3 Diagnosis

Imaging:

• CT/MRI: Disproportionately enlarged ventricles (Evans index >0.3) with normal or small sulci over convexities
• DESH (Disproportionately Enlarged Subarachnoid-Space Hydrocephalus) on MRI, high specificity
• Tight sulci over vertex

CSF Tap Test (Miller Fisher Test):

• LP with removal of 30-50 mL CSF
• Positive if gait improves within 24-72 hours
• Sensitivity 50-60%; specificity ~80%
• Positive tap test predicts good shunting outcome

Extended CSF Drainage (External lumbar drain):

• 3-5 days of continuous drainage
• Higher sensitivity than tap test for predicting shunt response

8.4 Treatment

Ventriculoperitoneal (VP) shunt:

• Definitive treatment for idiopathic NPH
• Best outcomes: young age, short symptom duration, predominant gait symptoms, positive tap test
• Complications: over-drainage (subdural hematoma), infection, shunt failure
• Response: Gait improves best (50-80%), continence improves (50-60%), cognition improves least (25-40%)

PART 9: REVERSIBLE DEMENTIAS

9.1 Mnemonic: "DEMENTIAS"

9.2 Key Reversible Causes

Hypothyroidism

• Cognitive slowing, memory impairment, depression, psychosis ("myxoedema madness")
• Check: TSH, free T4
• Treatment: levothyroxine → cognitive improvement usually within 6-12 weeks

Vitamin B12 Deficiency

• Combined subacute degeneration of spinal cord + cognitive impairment
• Psychiatric: depression, psychosis, irritability
• Check: serum B12, homocysteine, methylmalonic acid (more sensitive)
• Treatment: B12 supplementation (IM hydroxocobalamin or high-dose oral)

Neurosyphilis

• Dementia, personality change, psychiatric symptoms; classic tabes dorsalis + GPI (General Paralysis of the Insane)
• Check: VDRL/RPR (blood), TPHA/FTA-abs, CSF VDRL (definitive)
• Treatment: penicillin G IV

HIV-Associated Neurocognitive Disorder (HAND)

• Spectrum from asymptomatic to HIV-associated dementia (HAD)
• Subcortical pattern: psychomotor slowing, frontal-executive deficits
• Pathology: activated microglia, giant cells, HIV encephalitis
• Treatment: ART (antiretroviral therapy), reverses early HAND

Depression: Pseudodementia

• Cognitive impairment due to depression, mimicking dementia
• Features: onset correlated with depressive episode, subjective complaints > objective deficits, "I don't know" answers, inconsistent performance
• Kiloh (1961) coined the term pseudodementia

Differentiating Pseudodementia (Depression) from True Dementia:

Medication-Induced Cognitive Impairment

• Anticholinergics (TCAs, antihistamines, oxybutynin, antipsychotics with high ACh blockade)
• Benzodiazepines (sedation, anterograde amnesia)
• Opioids (especially in elderly)
• Corticosteroids (delirium, cognitive impairment)
• Alcohol (Wernicke-Korsakoff, alcoholic dementia)

PART 10: CREUTZFELDT-JAKOB DISEASE (CJD)

10.1 Prion Diseases

Prion diseases = Transmissible Spongiform Encephalopathies (TSEs), caused by misfolded prion proteins (PrPSc) that propagate by converting normal PrPC to PrPSc.

Types of CJD:

10.2 Sporadic CJD: Clinical Features

• Rapidly progressive dementia (weeks-months)
• Myoclonus (present in 90%, stimulus-sensitive)
• Cerebellar ataxia, visual disturbances
• Extrapyramidal signs
• Akinetic mutism (terminal stage)
• Median survival: 5-6 months; 85% die within 1 year

10.3 Investigations in CJD

10.4 Variant CJD (vCJD)

• Linked to BSE ("mad cow disease")
• Affects younger patients (mean age 28)
• Psychiatric onset: depression, anxiety, behavioral change (before dementia)
• Ataxia, sensory symptoms prominent
• EEG: No PSWC (unlike sCJD)
• MRI: "Pulvinar sign", bilateral high signal in posterior thalamus (DWI/FLAIR)
• CSF: 14-3-3 negative; tonsil biopsy can show PrPSc
• Survival: 12-14 months

PART 11: BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA (BPSD)

11.1 Overview

BPSD = Non-cognitive symptoms of dementia, occurs in 90% of patients during the course of dementia.

11.2 Types of BPSD

Most common delusion in AD: Theft delusion ("someone is stealing my things"), misidentification of misplaced objects

Most common BPSD: Apathy (~70%)

11.3 Assessment of BPSD

Neuropsychiatric Inventory (NPI), Cummings:

• 12 domains: delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, sleep, appetite
• Informant-based
• Rates frequency (1-4) and severity (1-3) separately
• NPI score = frequency × severity for each domain

Cohen-Mansfield Agitation Inventory (CMAI): Rates agitation severity

11.4 Non-Pharmacological Interventions (First-Line)

• Person-centered care: Know the person's history, preferences, lifelong habits
• Validation therapy: Accept and enter the patient's reality rather than correcting
• Music therapy: Strong evidence for agitation, particularly personalized music
• Bright light therapy: Sleep disturbances, sundowning
• Exercise: Reduces agitation, improves sleep
• Reminiscence therapy: Photos, objects from past; reduces depression
• Structured activities: Reduces wandering, agitation
• Environmental modification: Safe, uncluttered, low stimulation at night
• Caregiver training: Most important intervention

11.5 Pharmacological Management of BPSD

Agitation/Psychosis:

Depression in Dementia:

• SSRIs: sertraline, citalopram (escitalopram preferred in elderly, less CYP450 interactions)
• Avoid TCAs (anticholinergic effects)
• Mirtazapine: if sleep disturbance + depression + appetite loss

Anxiety:

• SSRIs first-line
• Low-dose buspirone
• Avoid benzodiazepines (falls, cognitive worsening, paradoxical agitation)

Sleep Disturbance:

• Melatonin 2-10mg (safest)
• Low-dose trazodone 25-100mg
• Mirtazapine 7.5-15mg
• Avoid diphenhydramine (anticholinergic), benzodiazepines (if possible)

Agitation, Memantine:

• Some evidence for reducing agitation in moderate-severe AD
• Safer profile than antipsychotics

CATIE-AD Study (2006): No significant cognitive or behavioral benefit of olanzapine, quetiapine, or risperidone over placebo in AD-related BPSD; significant adverse effects noted.

PART 12: COGNITIVE ASSESSMENT TOOLS

12.1 Mini-Mental State Examination (MMSE): Folstein (1975)

• Most widely used bedside cognitive screen
• Time: 5-10 minutes
• Total: 30 points

Scoring:

• 24-30: Normal
• 18-23: Mild impairment
• 12-17: Moderate impairment
• 0-11: Severe impairment

Limitations:

• Ceiling effect in highly educated
• Floor effect in low literacy
• Misses frontal and executive dysfunction
• Language/cultural bias
• Copyrighted (fees for use)

12.2 Montreal Cognitive Assessment (MoCA): Nasreddine (2005)

• Better sensitivity than MMSE for MCI
• Time: 10-15 minutes
• Total: 30 points

Scoring: ≥26 = Normal; Add 1 point if education ≤12 years

Advantages over MMSE: Better for MCI, executive function, visuospatial domains; free; multilingual versions available

12.3 Addenbrooke's Cognitive Examination-III (ACE-III)

• Time: 15-20 minutes
• Total: 100 points
• Subtests: Attention (18), Memory (26), Fluency (14), Language (26), Visuospatial (16)
• Cut-off: ≤88 suggests cognitive impairment
• VLOM ratio: [Verbal fluency + Language] / [Orientation + Memory delayed recall], helps differentiate AD (VLOM <2.2) from FTD (VLOM ≥3.2)

12.4 Clinical Dementia Rating (CDR): Morris (1993)

• Staging instrument (not a screening test)
• Rated across 6 domains: Memory, Orientation, Judgment/Problem Solving, Community Affairs, Home & Hobbies, Personal Care

CDR Sum of Boxes (CDR-SoB): 0-18; more sensitive to change; used in clinical trials

12.5 ADAS-Cog (Alzheimer's Disease Assessment Scale: Cognitive Subscale)

• 11-item scale
• Total: 70 points (higher score = worse)
• Used in clinical trials (primary endpoint in most AD drug trials)
• Includes word recall, naming, following commands, constructional praxis, ideational praxis, orientation, word recognition, comprehension, word-finding, recall test instructions

12.6 Clock Drawing Test (CDT)

• Simple, rapid, culturally fair
• Tests: executive function (planning), visuospatial, language comprehension
• Score 1-10 (Shulman scoring); 0-4 (Watson scoring)
• Sensitive to frontal and parietal dysfunction

12.7 Neuropsychiatric Inventory (NPI)

• 12-domain informant-based assessment of BPSD
• Each domain: screening question → if positive, frequency (1-4) and severity (1-3) → NPI score per domain = F × S (max 12 per domain)
• Total max: 144
• Also measures caregiver distress per domain (0-5)

PART 13: CAREGIVER BURDEN

13.1 Overview

Family caregivers of dementia patients are the "hidden second patients." The progressive, prolonged nature of dementia combined with BPSD creates one of the heaviest caregiver burdens of any disease.

India-specific: ~85-90% of dementia care is provided by family members; no structured respite care infrastructure; significant financial, physical, and psychological burden.

13.2 Components of Caregiver Burden

13.3 Assessment Tools

Zarit Burden Interview (ZBI): 22-item; most widely used; total 0-88; higher = greater burden

• Little burden: 0-20
• Mild-moderate: 21-40
• Moderate-severe: 41-60
• Severe: 61-88

Caregiver Strain Index (CSI): 13-item; quick screen

13.4 Interventions for Caregiver Burden

• Psychoeducation: Disease course, managing BPSD, what to expect
• Skill training: Communication techniques, managing challenging behaviors
• Support groups: Significant benefit for emotional support and practical advice
• Respite care: Day centers, temporary placement, reduces burnout
• Individual psychological therapy: CBT for depression, acceptance-based approaches
• Self-care promotion: Sleep, own medical appointments
• Advance care planning: Reduces emergency decision-making burden

PART 14: LEGAL AND ETHICAL ISSUES IN DEMENTIA

14.1 Capacity Assessment

Capacity is decision-specific and time-specific. A patient with dementia may have capacity for some decisions (e.g., choosing lunch) but not others (e.g., complex financial decisions).

Four Components of Capacity (MacCAT-T framework):

1. Understanding: Can the patient understand the relevant information?
2. Appreciation: Can they appreciate how it applies to their situation?
3. Reasoning: Can they reason about the options?
4. Communication: Can they express a consistent choice?

Key Principle: Diagnosis of dementia does NOT automatically mean lack of capacity.

14.2 Legal Instruments

India: Mental Healthcare Act 2017 includes provisions for advance directives and nominated representatives.

14.3 Driving and Dementia

• Any stage of dementia raises concerns about driving safety
• Mild dementia: individualized assessment required (on-road test, neuropsychological testing)
• Moderate-severe dementia: generally cannot drive safely
• Ethical duty to warn vs confidentiality, varies by jurisdiction; India has no mandatory reporting law currently

14.4 Elder Abuse

• Higher in dementia (80% of elder abuse involves some cognitive impairment)
• Financial exploitation: most common type in dementia
• Physical abuse, neglect, emotional abuse
• Assessment: Elder Abuse Suspicion Index (EASI)
• Mandatory reporting: varies by state in India

PART 15: DELIRIUM SUPERIMPOSED ON DEMENTIA (DSD)

15.1 Overview

DSD is one of the most clinically challenging scenarios, dementia increases the risk of delirium 2-5 fold, and delirium worsens the trajectory of dementia.

Prevalence: 22-89% of dementia patients admitted to hospital develop delirium

15.2 Differentiating Delirium from Dementia vs DSD

15.3 Confusion Assessment Method (CAM)

Delirium diagnosis requires features 1+2 PLUS either 3 or 4:

1. Acute onset and fluctuating course
2. Inattention
3. Disorganized thinking
4. Altered level of consciousness

15.4 Management of DSD

• Identify and treat underlying precipitant (infection, metabolic, medications, pain)
• Non-pharmacological first: reorientation, familiar faces, lighting, early mobilization, hearing aids/glasses
• Pharmacological: low-dose haloperidol (0.25-1mg), cautiously; risperidone
• NEVER benzodiazepines as first-line (worsen confusion, increase fall risk)
• Avoid antipsychotics in DLB-related DSD (neuroleptic sensitivity)

PART 16: SUMMARY TABLE: KEY COMPARISONS

16.1 Differentiating the Four Major Dementias

QUICK REFERENCE: EXAM FACTS

1. Most common dementia worldwide: Alzheimer's disease (60-70%)
2. Most common dementia in under-65s: Frontotemporal dementia
3. India dementia prevalence: 5.3 million (ARDSI data)
4. Most common hallucination in DLB: well-formed visual hallucinations
5. 1-year rule: DLB (dementia ≤1 year before/after parkinsonism) vs PDD (>1 year)
6. Neuroleptic sensitivity: DLB, avoid conventional antipsychotics
7. Hakim-Adams triad: gait + incontinence + dementia (NPH)
8. Hachinski score: ≥7 = VaD; ≤4 = AD
9. Most amyloidogenic Aβ species: Aβ42
10. Best correlate of cognitive decline in AD: synaptic loss (not plaques/tangles)
11. APOE4 risk: 3-4x heterozygote; 8-12x homozygote
12. First ChEI: Tacrine (now obsolete, hepatotoxic)
13. Dual inhibitor (AChE + BuChE): Rivastigmine
14. EEG finding in CJD: periodic sharp wave complexes (PSWC)
15. Most common pathological tau in Pick's disease: 3R tau
16. C9orf72: most common cause of familial FTD + ALS
17. Pseudodementia: coined by Kiloh (1961)
18. MoCA normal cutoff: ≥26 (add 1 if education ≤12 years)
19. MMSE max score: 30; CDR-SoB max: 18
20. Lecanemab trial: CLARITY-AD; 27% slowing of decline

Sources: Kaplan & Sadock's Synopsis of Psychiatry 12th Ed, Oxford Textbook of Psychiatry 6th Ed, Cummings' Neuropsychiatry and Behavioral Neuroscience 3rd Ed, NIA-AA 2018 Research Framework, McKeith Criteria 2017, Rascovsky Criteria 2011

Model Answers

ANSWER 1: Define dementia. Classify and describe the clinical features of Alzheimer's disease. Add a note on its pharmacological management.

Definition (1 mark)

Dementia is a syndrome of acquired, persistent, progressive cognitive decline affecting two or more cognitive domains, including memory, language, executive function, visuospatial abilities, or social cognition, representing a decline from a previously higher level of functioning, and severe enough to interfere with daily occupational or social activities.

Per DSM-5: Now termed Major Neurocognitive Disorder (Major NCD). Per ICD-11: Dementia is retained as an overarching diagnostic category.

Classification of Dementia (2 marks)

By Aetiology:

By Reversibility: Reversible (~15%) vs Irreversible

By Age: Pre-senile (<65 years) vs Senile (≥65 years)

By Cortical Anatomy: Cortical (AD, FTD) vs Subcortical (VaD, DLB, PSP, HD) vs Mixed

Alzheimer's Disease: Pathology (3 marks)

Epidemiology: Most common dementia (60-70%); prevalence doubles every 5 years after age 65; India: ~5.3 million total dementia cases (ARDSI 2023), with AD comprising the majority.

Gross Pathology: Cortical atrophy predominantly affecting hippocampus, entorhinal cortex, and parietal and temporal association areas. Ventricular enlargement (ex vacuo).

Microscopic Hallmarks:

• Senile plaques, extracellular deposits of beta-amyloid (Aβ42) peptide; neuritic plaques are pathologically significant
• Neurofibrillary tangles (NFTs), intraneuronal accumulations of hyperphosphorylated tau protein in paired helical filaments; Braak staging I-VI
• Synaptic loss, the best histological correlate of cognitive decline

Neurochemistry: Marked reduction in acetylcholine (nucleus basalis of Meynert, 50-90%), noradrenaline, serotonin; glutamatergic dysregulation.

Genetics: APP (chromosome 21), PSEN1 (chromosome 14), PSEN2 (chromosome 1), early-onset familial; APOE4 (chromosome 19), risk factor for late-onset sporadic.

Clinical Features (2 marks)

Early (Mild) Stage:

• Episodic memory impairment, forgetting recent events, appointments
• Word-finding difficulties (anomia)
• Spatial disorientation in unfamiliar environments
• Mild impairment in instrumental ADLs (finances, medications)
• Insight often preserved

Middle (Moderate) Stage:

• Progressive memory loss; retrograde involvement
• Impaired orientation (time, then place)
• Language deterioration (paraphasia, reduced vocabulary)
• Apraxia, agnosia, acalculia
• Behavioural and psychological symptoms (delusions of theft, wandering, agitation)
• Dependent in basic ADLs

Late (Severe) Stage:

• Severe global cognitive decline
• Non-communicative
• Double incontinence
• Motor signs (rigidity, myoclonus in late stages)
• Bedridden, aspiration, death from intercurrent illness

MMSE Range: Mild ~18-23; Moderate ~12-17; Severe 0-11

Pharmacological Management (2 marks)

Cholinesterase Inhibitors (mild-moderate):

Swipe to compare →

NMDA Antagonist (moderate-severe):

• Memantine 5→20mg OD, reduces glutamatergic excitotoxicity
• Can combine with donepezil for additive benefit (Tariot et al., 2004)

Newer Agents (early AD with biomarker confirmation):

• Lecanemab (Leqembi), anti-Aβ protofibrils antibody; 27% slowing of decline (CLARITY-AD, 2022)
• Donanemab, FDA approved 2024; TRAILBLAZER-ALZ 2 trial
• Risk of ARIA (amyloid-related imaging abnormalities), requires MRI monitoring

BPSD Management: Risperidone (best evidence) for psychosis/agitation; SSRIs for depression; melatonin for sleep; non-pharmacological interventions first-line.

ANSWER 2: Describe the clinical features, diagnosis, and management of Dementia with Lewy Bodies (DLB). Highlight the differences from Parkinson's Disease Dementia.

Definition and Overview (1 mark)

DLB is a neurodegenerative dementia characterised by the pathological accumulation of alpha-synuclein (Lewy bodies) in cortical and subcortical neurons, producing a clinical triad of fluctuating cognition, recurrent visual hallucinations, and parkinsonism. It is the second most common neurodegenerative dementia (~15-20%).

Pathology (2 marks)

• Lewy bodies: Intraneuronal inclusions of misfolded alpha-synuclein; eosinophilic core with radiating halo
• Distribution: cortical > subcortical (in DLB); brainstem predominant (in PD)
• Neurochemistry: Severe cholinergic deficit (greater than AD); dopaminergic deficit (nigrostriatal); noradrenergic and serotonergic loss
• Braak staging: stages 5-6 (neocortical involvement) in DLB

McKeith Criteria 2017: Clinical Features (3 marks)

Essential: Progressive dementia interfering with daily function; prominent early deficits in attention, executive function, visuospatial ability; memory may be relatively preserved initially.

Core Clinical Features (need 2 for "probable"):

Supportive Features:

• Severe neuroleptic sensitivity (hallmark, can be fatal)
• Postural instability, falls, syncope
• Autonomic dysfunction (orthostatic hypotension, constipation)
• Neuropsychiatric: depression, anxiety, delusions
• Hypersomnia, hyposmia

Indicative Biomarkers:

• Reduced DAT uptake on DaTSCAN (SPECT)
• Abnormal cardiac MIBG scintigraphy
• PSG confirmation of REM sleep without atonia

Diagnosis (2 marks)

• Clinical diagnosis per McKeith 2017 criteria
• DaTSCAN: reduced striatal dopamine transporter uptake, distinguishes DLB from AD
• EEG: posterior slow wave activity; complex transient waves
• MRI: relative preservation of medial temporal lobe (vs AD); generalised atrophy
• FDG-PET: occipital hypometabolism (distinctive, preserved in AD)
• Neuropsychological testing: early visuospatial and attentional deficits

Management (2 marks)

Cognitive: Rivastigmine (approved; significant benefit given severe cholinergic deficit); donepezil (off-label)

Parkinsonism: Levodopa (modest benefit; may worsen psychosis); avoid dopamine agonists

Psychosis, CRITICAL POINT:

• AVOID conventional antipsychotics (haloperidol, chlorpromazine), neuroleptic sensitivity reaction (30-50%): severe rigidity, autonomic crisis, accelerated cognitive decline, death
• Use ONLY: quetiapine (low dose) or clozapine (with CBC monitoring)

Sleep (RBD): Clonazepam 0.25-2mg nocte; melatonin 3-12mg

Depression: SSRIs (sertraline, escitalopram)

DLB vs PDD (Differences) (on request or as note):

ANSWER 3: Classify Frontotemporal Dementia (FTD). Describe the clinical features of behavioral variant FTD (bvFTD) and its management.

Definition and Overview (1 mark)

Frontotemporal dementia (FTD) encompasses a group of neurodegenerative conditions characterised by progressive degeneration of the frontal and/or temporal lobes, presenting with prominent changes in behaviour, personality, or language. It is the most common dementia in those under 65 years (peak onset 45-65 years) and the third most common neurodegenerative dementia overall.

Classification (2 marks)

Clinical Syndromes:

Associated Syndromes (FTD spectrum):

• Progressive Supranuclear Palsy (PSP)
• Corticobasal Degeneration (CBD)
• FTD-MND (FTD with Motor Neuron Disease), TDP-43 pathology, C9orf72 mutation

Neuropathological Classification:

• FTLD-Tau (Pick's disease, CBD, PSP)
• FTLD-TDP (~50%; includes FTD-MND)
• FTLD-FUS (rare)

bvFTD: Rascovsky Criteria 2011 (3 marks)

Requires 3 of 6 core features for Possible bvFTD:

1. Disinhibition:

• Socially inappropriate behaviour (offensive remarks, physical impropriety)
• Loss of social tact and manners
• Impulsive, reckless actions (inappropriate spending, sexual disinhibition)

2. Apathy / Inertia:

• Loss of motivation and drive
• Persists throughout the day (unlike depression which may fluctuate)
• Reduced spontaneous behaviour, social withdrawal

3. Loss of Sympathy / Empathy:

• Diminished response to others' emotions
• Change in social relationships
• Indifference to close family members

4. Perseverative / Compulsive Behaviour:

• Stereotyped repetitive acts (tapping, humming, clapping)
• Ritual behaviours, fixed routines
• Hoarding, collecting
• Dietary changes (preference for sweets, carbohydrates, specific foods)

5. Hyperorality and Dietary Changes:

• Oral fixation; putting objects in mouth
• Gluttony, food cramming
• Altered food preferences; increased alcohol/tobacco

6. Neuropsychological Profile:

• Executive dysfunction (planning, abstraction, working memory)
• Relative sparing of memory (episodic) and visuospatial in early stages
• Frontal release signs (snout, grasp reflex)

Important: Insight is impaired, patient does not recognise their behaviour as abnormal.

Memory Pattern: Unlike AD, episodic memory is relatively preserved early in bvFTD. This is a key distinction.

Imaging:

• MRI: frontal and anterior temporal atrophy (bilateral, often asymmetric)
• FDG-PET: frontal and anterior temporal hypometabolism
• DaTSCAN: typically normal (unlike DLB)

Genetics (on request) (1 mark)

• MAPT (chromosome 17): tau mutations
• GRN/Progranulin (chromosome 17): TDP-43 pathology
• C9orf72 (chromosome 9): most common familial cause (hexanucleotide repeat expansion); also causes familial ALS

Management (2 marks)

No disease-modifying therapy.

Behavioural Symptoms:

• SSRIs (sertraline 50-200mg, fluvoxamine), first-line for disinhibition, compulsive behaviours, hyperorality, aggression; evidence from open-label studies
• Low-dose atypical antipsychotics (quetiapine, olanzapine) for severe agitation/aggression
• Avoid ChEIs, no evidence; galantamine may worsen hyperorality
• Avoid memantine, conflicting evidence; some suggest worsening

Non-Pharmacological:

• Structured routine (reduces compulsive behaviours)
• Redirection techniques
• Environmental safety (wandering, impulsive acts)
• Caregiver education: empathy deficits explained, carers must understand "he knows who I am but doesn't care how I feel"

Genetic Counselling:

• Autosomal dominant families (MAPT, GRN, C9orf72), genetic testing for at-risk members
• Predictive testing protocols

Speech-Language Therapy: For PPA variants

ANSWER 4: Discuss Normal Pressure Hydrocephalus: clinical features, diagnosis, and treatment.

Definition (1 mark)

Normal Pressure Hydrocephalus (NPH) is a clinical syndrome characterised by the triad of gait disturbance, urinary incontinence, and cognitive impairment, in the setting of ventriculomegaly on imaging with normal or intermittently normal cerebrospinal fluid pressure on lumbar puncture. It was first described by Adams and Hakim (1965).

Aetiology and Pathophysiology (2 marks)

Idiopathic NPH (iNPH): No identifiable cause; most common in elderly

Secondary NPH: Follows known insult, subarachnoid haemorrhage, head injury, meningitis, prior neurosurgery

Pathophysiology:

• Impaired CSF absorption at the arachnoid villi (Pacchionian granulations)
• CSF accumulation → ventricular enlargement
• Normal or intermittently elevated CSF pressure (pressure waves occur transiently)
• Ventricular expansion compresses periventricular white matter, especially frontal-subcortical circuits
• Disruption of frontosubcortical pathways → gait, continence, cognition triad

Clinical Features: Hakim-Adams Triad (3 marks)

Order of Appearance: Gait → Incontinence → Dementia (the G-I-D sequence)

Important nuances:

• Not all three features present in all patients
• Gait disturbance is earliest and most prominent
• Cognitive impairment is often mild to moderate
• Differentiation of gait from Parkinson's: NPH has no tremor, arm swing may be preserved, no rigidity at initiation, improved by cadence cues inconsistently

Investigations and Diagnosis (2 marks)

Imaging:

• CT/MRI brain: ventriculomegaly (Evans index >0.3: bifrontal horn diameter / internal skull diameter); small or absent cortical sulci over the vertex (high convexity); DESH pattern on MRI (Disproportionately Enlarged Subarachnoid-Space Hydrocephalus, periventricular edema with sulcal obliteration)
• MRI: periventricular signal changes, aqueductal flow void (on CINE MRI)

Lumbar Puncture:

• Opening pressure: <200 mm H2O (normal), defining criterion
• CSF composition: normal

CSF Tap Test (Miller Fisher Test):

• Remove 30-50 mL CSF
• Assess gait before and 1-24-72 hours after
• Positive if gait improves, predicts shunt response (sensitivity 50-60%, specificity ~80%)

Extended Lumbar Drain:

• 3-5 days continuous CSF drainage (~150-200 mL/day)
• Higher sensitivity for predicting shunt response

Neuropsychological Testing: Pre- and post-tap comparison; documents baseline cognitive profile

Treatment (2 marks)

Ventriculoperitoneal (VP) Shunt:

• Definitive treatment
• Best response: young age, short duration, gait-predominant presentation, positive tap test
• Response rates: gait 50-80%, incontinence 40-60%, cognition 25-40%
• Complications: over-drainage (subdural haematoma), use programmable pressure valves; infection; shunt failure; intracranial haemorrhage

Programmable Valves: Preferred, allow non-invasive pressure adjustment post-implantation

Endoscopic Third Ventriculostomy (ETV): Alternative in selected cases

ANSWER 5: Write an essay on reversible causes of dementia with special emphasis on pseudodementia.

Definition and Importance (1 mark)

Reversible dementia refers to cognitive impairment that, when the underlying cause is identified and treated, results in partial or complete improvement. Approximately 15% of dementia presentations have a potentially reversible component. Identifying reversible causes is critical because many are treatable and can prevent permanent cognitive damage.

Classification: "DEMENTIAS" Mnemonic (2 marks)

Key Reversible Causes (3 marks)

Hypothyroidism:

• Symptoms: cognitive slowing, memory impairment, psychomotor retardation, depression, psychosis ("myxoedema madness")
• Diagnosis: TSH elevated, free T4 low
• Treatment: levothyroxine, cognitive improvement within 6-12 weeks

Vitamin B12 Deficiency:

• Psychiatric manifestations: depression, irritability, mania, psychosis
• Cognitive: slowing, memory impairment, confusion
• Neurological: subacute combined degeneration of spinal cord
• Investigations: serum B12 <200 pg/mL; methylmalonic acid (elevated, more sensitive); homocysteine (elevated)
• Treatment: IM hydroxocobalamin; high-dose oral B12 (1000mcg/day)

Neurosyphilis:

• General Paralysis of the Insane (GPI): dementia, personality change, grandiose delusions, dysarthria, Argyll Robertson pupil
• Tabes dorsalis component
• Investigations: blood VDRL/RPR (screening), TPHA/FTA-ABS (confirmatory), CSF VDRL
• Treatment: penicillin G IV 18-24 million units/day × 10-14 days

HIV-Associated Neurocognitive Disorder (HAND):

• Spectrum: asymptomatic NCI → MND → HAD
• Subcortical pattern: psychomotor slowing, executive dysfunction
• Diagnosis: CSF HIV RNA, neuroimaging, neuropsychological battery
• Treatment: ART (combination antiretroviral), can reverse early HAND

Medication-Induced:

• Anticholinergics (most common iatrogenic cause of cognitive impairment in elderly)
• Benzodiazepines (anterograde amnesia, sedation)
• Review and rationalise polypharmacy

Pseudodementia: Depressive Pseudodementia (2 marks)

Definition: Pseudodementia (term coined by Kiloh, 1961) refers to a reversible, dementia-like cognitive syndrome occurring in the context of a primary psychiatric disorder, most commonly major depression, that mimics neurodegenerative dementia but resolves with appropriate psychiatric treatment.

Pathophysiology: Depression impairs attention, concentration, working memory, and motivation, producing objective cognitive deficits. Neurobiological correlates include HPA axis dysregulation, hippocampal volume loss (reversible), and reduced prefrontal activity.

Differential Features:

Management:

• Treat underlying depression: SSRIs first-line (sertraline, escitalopram, mirtazapine)
• ECT if severe depression with cognitive impairment, often rapid improvement
• Neuropsychological follow-up to confirm cognitive recovery
• Note: pseudodementia is a risk factor for later true dementia (15-20% convert over 3 years)

ANSWER 6: Describe the clinical features and management of Behavioral and Psychological Symptoms of Dementia (BPSD).

Definition and Epidemiology (1 mark)

Behavioral and Psychological Symptoms of Dementia (BPSD), also known as neuropsychiatric symptoms of dementia, refers to the non-cognitive manifestations of dementia including disturbances of perception, thought content, mood, and behaviour. BPSD affects approximately 90% of patients with dementia at some point in their illness course. They are the primary drivers of caregiver distress and institutionalisation.

Classification (2 marks)

Most common delusion in AD: Theft delusion (misattributing misplaced objects to theft)

Most common BPSD overall: Apathy (~70%)

Most distressing for carers: Agitation and aggression

Assessment, NPI (Neuropsychiatric Inventory, Cummings): 12-domain informant-based scale; each domain scored as frequency (1-4) × severity (1-3); max 144 points; also records caregiver distress per domain.

Non-Pharmacological Management: FIRST LINE (3 marks)

Principle: Identify and address triggers (pain, infection, environment, unmet needs) before any pharmacological intervention.

Pharmacological Management (2 marks)

Agitation/Psychosis:

CATIE-AD Study (2006): No significant efficacy advantage of risperidone, olanzapine, or quetiapine over placebo; significant adverse effects. Reinforces non-pharmacological priority.

Depression in Dementia:

• SSRIs: sertraline 50mg, escitalopram 5-10mg
• Mirtazapine 7.5-30mg (if depression + insomnia + anorexia)
• Avoid TCAs (anticholinergic burden)

Anxiety:

• SSRIs first-line
• Buspirone 5-10mg TDS
• Avoid benzodiazepines if possible (falls, paradoxical agitation, cognitive worsening)

Sleep Disturbance:

• Melatonin 2-10mg nocte (safest)
• Trazodone 25-100mg nocte
• Mirtazapine 7.5-15mg
• Avoid antihistamines (anticholinergic), benzodiazepines (falls, cognitive worsening)

Summary Approach (2 marks)

Step 1: Identify and treat reversible precipitants (pain, UTI, constipation, medication toxicity)

Step 2: Non-pharmacological interventions (tailored to symptom type)

Step 3: Pharmacological only if above fails or patient/carer safety at risk; reassess every 3 months; attempt dose reduction after 3-6 months of stability

ANSWER 7: Discuss the role of biomarkers in the diagnosis of Alzheimer's disease.

Introduction (1 mark)

Biomarkers in Alzheimer's disease (AD) are measurable biological parameters that reflect underlying pathological processes, enabling diagnosis in the pre-symptomatic or early symptomatic stages, before significant neurodegeneration. The NIA-AA 2018 Research Framework (Jack et al.) operationalised the A/T/N classification system, shifting AD diagnosis from purely clinical to biologically defined.

Rationale for Biomarkers (1 mark)

Clinical diagnosis of AD has ~80% accuracy when performed by dementia specialists. Biomarkers improve diagnostic accuracy to >90%. They are essential for:

• Entry criteria in clinical trials (anti-amyloid therapies require amyloid confirmation)
• Early/preclinical diagnosis enabling preventive intervention
• Differential diagnosis from non-AD dementias
• Monitoring disease progression and treatment response

A/T/N Classification (2 marks)

Profiles:

• A+/T-/N- = Alzheimer's pathological change (no tauopathy)
• A+/T+/N- = Alzheimer's disease (early)
• A+/T+/N+ = Alzheimer's disease (established neurodegeneration)
• A-/T+/N+ = Non-AD tauopathy

CSF Biomarkers (2 marks)

CSF biomarkers can detect pathological changes 10-15 years before clinical symptoms.

Neuroimaging Biomarkers (2 marks)

Structural MRI:

• Medial temporal lobe atrophy (MTA), especially hippocampus and entorhinal cortex
• Scheltens MTA scale (0-4): score ≥2 suggests AD
• VBM (voxel-based morphometry): global atrophy pattern temporo-parietal > frontal

Amyloid PET (Florbetapir, Flutemetamol, Florbetaben):

• Positive: diffuse cortical binding (beyond white matter)
• Sensitivity ~96%, Specificity ~93%
• Presence of amyloid does not equal AD (20-30% cognitively normal elderly have amyloid+)
• FDA-approved; required for anti-amyloid therapy eligibility

Tau PET (Flortaucipir/AV-1451):

• Images neurofibrillary tangles directly
• Follows Braak staging hierarchically
• Correlates better with cognitive symptoms than amyloid PET

FDG-PET:

• AD pattern: bilateral temporo-parietal + posterior cingulate hypometabolism
• Spares primary sensorimotor and occipital cortex until late
• Differentiates AD from FTD (frontal hypometabolism)

Blood Biomarkers (1 mark: emerging/recent advances)

Blood biomarkers represent the future of AD screening, enabling large-scale, low-cost, accessible detection before expensive PET or lumbar puncture.

ANSWER 8: Describe the clinical features, investigations, and management of Creutzfeldt-Jakob Disease (CJD).

Introduction and Classification (1 mark)

Creutzfeldt-Jakob Disease (CJD) is a rare, rapidly progressive, invariably fatal prion disease belonging to the group of Transmissible Spongiform Encephalopathies (TSEs). The causative agent is PrPSc, a misfolded, protease-resistant isoform of the normal cellular prion protein (PrPC) that propagates by inducing conformational change in normal PrPC.

Types:

Clinical Features (3 marks)

Sporadic CJD:

• Onset: Mean age 60-65 years; median survival 5-6 months (85% die within 1 year)
• Prodrome: anxiety, depression, insomnia, vague cognitive complaints
• Rapidly progressive dementia (weeks to months, HALLMARK)
• Myoclonus, stimulus-sensitive; present in 90%; pathognomonic in context
• Cerebellar ataxia, dysarthria
• Extrapyramidal signs (rigidity, dystonia)
• Visual disturbances (cortical blindness, Heidenhain variant)
• Pyramidal signs
• Akinetic mutism, terminal stage
• Death: aspiration pneumonia, sepsis

Variant CJD (vCJD):

• Onset: Much younger (mean 28 years), BSE-linked dietary exposure
• Psychiatric onset: depression, anxiety, withdrawal, personality change (6-12 months before neurological features)
• Sensory symptoms: dysaesthesias, pain (characteristic)
• Later: progressive dementia, ataxia, involuntary movements
• NO periodic EEG changes (unlike sCJD)
• Survival: 12-14 months (longer than sCJD)

Investigations (2 marks)

WHO Diagnostic Criteria (Sporadic CJD):

• Definite: neuropathological/immunohistochemical confirmation
• Probable: rapidly progressive dementia + EEG PSWC OR positive RT-QuIC + ≥2 of (myoclonus, visual, cerebellar, pyramidal/extrapyramidal, akinetic mutism)
• Possible: does not meet above but <2 years progressive dementia

Management and Prognosis (2 marks)

No disease-modifying treatment exists. All CJD is fatal.

Palliative/Supportive Management:

• Symptom control: clonazepam for myoclonus; opioids for pain
• Hospice/palliative care: early involvement
• Psychological support: family counselling; anticipatory grief
• Infection control: universal precautions; CJD-contaminated instruments require special decontamination (autoclaving standard ineffective, requires 1M NaOH or 134°C extended autoclaving)

Notifiable Disease: CJD is a notifiable condition in most jurisdictions including India.

ANSWER 9: Discuss the assessment of cognitive function with reference to MMSE and MoCA.

Introduction (1 mark)

Cognitive assessment tools serve multiple functions in clinical practice: screening for cognitive impairment, staging severity, monitoring progression, and assessing treatment response. Brief bedside cognitive tests are essential first-line tools but must be interpreted in the context of age, education, cultural background, and sensory deficits.

MMSE: Mini Mental State Examination (Folstein et al., 1975) (3 marks)

Overview: 30-point screening tool; 5-10 minutes; most widely used globally; assesses orientation, registration, attention, recall, language, and visuospatial.

Scoring Thresholds:

• 27-30: Normal
• 24-26: Questionable/MCI range
• 18-23: Mild dementia
• 12-17: Moderate dementia
• 0-11: Severe dementia

Limitations:

• Ceiling effect in highly educated individuals (misses MCI)
• Floor effect in low literacy/education
• Does NOT assess frontal/executive function (planning, abstraction)
• Poor at detecting frontal or subcortical dementias (FTD, VaD)
• Language and cultural bias
• Copyrighted (Psychological Assessment Resources), fees apply

MoCA: Montreal Cognitive Assessment (Nasreddine et al., 2005) (3 marks)

Overview: 30-point screening tool; 10-15 minutes; developed specifically to detect MCI; better sensitivity for executive and visuospatial deficits.

Correction: Add 1 point if total education ≤12 years

Normal cutoff: ≥26/30 (adjusted)

Advantages over MMSE:

• Higher sensitivity for MCI (sensitivity ~90% vs MMSE ~18% for MCI)
• Includes executive and visuospatial tasks
• Detects frontal and subcortical dementias better
• Free; available in >50 languages
• Better for younger, educated patients

Comparison Table (2 marks)

Other Tools (1 mark)

• ACE-III (100 points): Comprehensive; VLOM ratio for AD vs FTD differentiation
• CDR (Clinical Dementia Rating): Staging; CDR-SoB tracks change
• ADAS-Cog (70 points): Gold standard for clinical trials
• Clock Drawing Test: Quick executive/visuospatial screen
• NPI: BPSD assessment (informant-based)

ANSWER 10: Discuss the vascular dementia: types, clinical features, Hachinski score, and management.

(Refer to Comparisons file D4 for full VaD vs AD table and to Study Notes Part 5 for comprehensive coverage.)

Definition and Overview (1 mark)

Vascular dementia (VaD) is cognitive impairment caused by cerebrovascular disease. It is the second most common cause of dementia (15-20% globally; ~30% in India due to high vascular risk factor burden). Pathologically heterogeneous, encompasses multiple subtypes linked by the underlying mechanism of vascular brain injury.

Types (2 marks)

Clinical Features (2 marks)

• Abrupt onset, stepwise course (each stroke = new step)
• Focal neurological deficits (hemiparesis, dysarthria, cranial nerve signs)
• Gait disturbance: marche a petit pas (subcortical VaD)
• Urinary incontinence: frontal-subcortical
• Emotional lability / emotional incontinence
• Executive dysfunction prominent; psychomotor slowing
• Memory: retrieval impairment > encoding (unlike AD)
• Depression: very common (post-stroke depression)

Hachinski Ischemic Score (2 marks)

Score ≥7 = VaD; Score ≤4 = AD; Score 5-6 = Mixed/inconclusive

Management (1 mark)

• Primary/secondary prevention: BP control (<130/80), diabetes control, antiplatelet therapy, statins, smoking cessation, exercise
• Cholinesterase inhibitors: modest evidence (donepezil approved in some countries for VaD)
• Memantine: some evidence
• No established disease-modifying therapy for VaD itself

ANSWERS 11–15: Additional High-Yield Topics

ANSWER 11: Caregiver burden in dementia: assessment and management

(Key points: Zarit Burden Interview 22-item/88 points; hidden second patient; psychoeducation + support groups + respite care; 50-70% of caregivers develop depression; India, 85-90% family-based care, no infrastructure)

ANSWER 12: MCI: definition, types, conversion rates, management

(Key: Petersen criteria; amnestic vs non-amnestic; 10-15%/year conversion; 20-30% revert; DSM-5 = Mild NCD; no approved pharmacotherapy; lifestyle modifications, hearing aids, exercise; monitoring)

ANSWER 13: Delirium superimposed on dementia: clinical features and management

(Key: 22-89% hospitalised dementia patients; acute on insidious onset; CAM criteria; identify and treat precipitant; non-pharmacological first; low-dose haloperidol cautiously; NEVER benzodiazepines first-line; never antipsychotics in DLB delirium)

ANSWER 14: Genetics of Alzheimer's disease

(Key: APP ch21 / PSEN1 ch14 / PSEN2 ch1, early-onset familial; APOE4 ch19, 3-4x hetero, 8-12x homo, risk not destiny; TREM2 ch6, microglial; Down syndrome, trisomy 21 → extra APP)

ANSWER 15: Ethical and legal issues in dementia: capacity and advance directives

(Key: Capacity = decision-specific + time-specific; 4 components of capacity, understand, appreciate, reason, communicate; MHA 2017 advance directives; driving assessment; testamentary capacity; financial exploitation most common elder abuse in dementia; guardianship)

Sources: Kaplan & Sadock's Synopsis of Psychiatry 12th Ed, Oxford Textbook of Psychiatry 6th Ed, Cummings' Neuropsychiatry and Behavioral Neuroscience 3rd Ed

Mnemonics & Memory Tricks

MNEMONIC 1: Reversible Causes of Dementia: "DEMENTIAS"

Swipe to compare →

MNEMONIC 2: NPH Triad: "The 3 Ws"

MNEMONIC 3: DLB Core Features: "FLiRP"

MNEMONIC 4: Hachinski Ischemic Score Items: "A STEP FRESH"

Features that score 2 points (remember separately): Abrupt onset (2), Fluctuating course (2), History of strokes (2), Focal symptoms (2), Focal signs (2)

MNEMONIC 5: Alzheimer's Genetics: "APP PSEN APOE"

• APP → Chromosome 21 (same as Down syndrome → universal AD)
• PSEN1 → Chromosome 14 (most common familial AD cause)
• PSEN2 → Chromosome 1 (least penetrant familial)
• APOE4 → Chromosome 19 (sporadic risk factor, "19 rhymes with fine wine, and APOE is about late-life risk")

MNEMONIC 6: FTD Behavioral Variant Features: "DELPHI" (Rascovsky Criteria)

MNEMONIC 7: Cholinesterase Inhibitors: "Don Ri Gal"

MNEMONIC 8: CJD Investigations: "ERT"

MNEMONIC 9: Tau vs Amyloid: "TAU LATER, AMYLOID FIRST"

1. Amyloid accumulates FIRST (15-20 years before symptoms), CSF Aβ42↓, amyloid PET+
2. Tau tangles follow (10-15 years before symptoms), CSF p-tau↑, tau PET+
3. Neurodegeneration last (5-10 years before symptoms), FDG-PET↓, MRI atrophy
4. Clinical symptoms appear LAST

MNEMONIC 10: Capacity Assessment: "UARC"

MNEMONIC 11: McKeith Biomarkers for DLB: "DAP" (Indicative Biomarkers)

MNEMONIC 12: Braak Stages (NFT Distribution in AD): "EC Hip Lim Neo"

MNEMONIC 13: FTD Genetics: "MAPT GRN C9"

MNEMONIC 14: BPSD Management Ladder: "N-P-R"

MNEMONIC 15: Differentiating AD from Pseudodementia: "COMPASS"

MNEMONIC 16 (Bonus): MMSE Domains: "ORARNCWCR" (Or A Rainbow Never Comes Without Colour Reading)

Total = 30

MNEMONIC 17 (Bonus): VaD Types: "MSSBC"

QUICK RECALL CARD

Sources: Kaplan & Sadock's Synopsis of Psychiatry 12th Ed, Oxford Textbook of Psychiatry 6th Ed, Cummings' Neuropsychiatry and Behavioral Neuroscience 3rd Ed

High-Yield Comparisons

TABLE 1: AD vs VaD vs DLB vs FTD: Master Comparison

Swipe to compare →

TABLE 2: MCI vs Mild Dementia (Major vs Mild NCD)

TABLE 3: MMSE vs MoCA: Full Comparison

TABLE 4: Donepezil vs Rivastigmine vs Galantamine

TABLE 5: DLB vs PDD: The 1-Year Rule

TABLE 6: Reversible vs Irreversible Dementias

TABLE 7: BPSD Pharmacotherapy Summary

TABLE 8: Cognitive Assessment Tools Comparison

TABLE 9: CJD Types Comparison

TABLE 10: AD Pharmacotherapy: Timeline and Mechanism

SUMMARY: Key Numbers to Memorise

Sources: Kaplan & Sadock's Synopsis of Psychiatry 12th Ed, Oxford Textbook of Psychiatry 6th Ed, Cummings' Neuropsychiatry and Behavioral Neuroscience 3rd Ed, McKeith 2017, Rascovsky 2011, NIA-AA 2018

PYQ Frequency Analysis

SECTION 1: FREQUENCY HEATMAP

Swipe to compare →

SECTION 2: QUESTION FORMAT ANALYSIS

10-Mark Long Essay Questions (Most Common for Dementias)

5-Mark Short Answer Questions (Frequent)

Viva / Short Note Patterns

SECTION 3: TOPIC-WISE QUESTION BANK (Reconstructed)

Alzheimer's Disease

1. Define dementia. Classify dementia and describe the clinical features and management of Alzheimer's disease. (10 marks)
2. Describe the neuropathological changes seen in Alzheimer's disease. (5 marks)
3. Write a note on the amyloid cascade hypothesis. (5 marks)
4. Describe the genetics of Alzheimer's disease. (5 marks)
5. What are the pharmacological options available for the management of Alzheimer's disease? (5 marks)
6. Write a note on biomarkers in the diagnosis of Alzheimer's disease. (5 marks)
7. Classify cholinesterase inhibitors. Describe their mechanism of action, indications, and side effects. (10 marks)
8. What is memantine? Describe its mechanism of action and role in dementia. (5 marks)
9. Write a note on newer disease-modifying therapies in Alzheimer's disease. (5 marks)
10. Describe the neuropsychological changes in Alzheimer's disease and their assessment. (10 marks)
11. What is APOE4? Describe its role in Alzheimer's disease. (5 marks)
12. Describe the A/T/N classification of Alzheimer's disease biomarkers. (5 marks)

Vascular Dementia

1. Classify vascular dementia. Describe the clinical features and Hachinski Ischemic Score. (10 marks)
2. Write a note on Hachinski Ischemic Score. (5 marks)
3. Describe the neuroimaging findings in vascular dementia. (5 marks)
4. Write a note on CADASIL. (5 marks)
5. Compare and contrast Alzheimer's disease and vascular dementia. (10 marks)

Dementia with Lewy Bodies

1. Describe the clinical features, diagnosis and management of Dementia with Lewy Bodies. Differentiate from Parkinson's Disease Dementia. (10 marks)
2. What is neuroleptic sensitivity in DLB? Describe its management. (5 marks)
3. Write a note on REM sleep behaviour disorder in dementia. (5 marks)
4. Describe the McKeith criteria for DLB. (5 marks)
5. What is DaTSCAN? Describe its role in DLB. (5 marks)

Frontotemporal Dementia

1. Classify frontotemporal dementia. Describe the clinical features and management of behavioral variant FTD. (10 marks)
2. Write a note on semantic dementia. (5 marks)
3. Describe the genetics of frontotemporal dementia. (5 marks)
4. Compare Pick's disease with Alzheimer's disease. (5 marks)
5. Write a note on progressive non-fluent aphasia. (5 marks)

NPH and Reversible Dementias

1. Describe Normal Pressure Hydrocephalus, clinical features, investigations and treatment. (10 marks)
2. Write an essay on reversible causes of dementia. (10 marks)
3. Describe pseudodementia, clinical features and differentiation from true dementia. (5 marks)
4. Write a note on the CSF tap test in NPH. (5 marks)
5. What is myxoedema madness? Describe cognitive features of hypothyroidism. (5 marks)
6. Describe the clinical features of neurosyphilis and its management. (5 marks)

BPSD

1. Describe the behavioral and psychological symptoms of dementia. Discuss their pharmacological and non-pharmacological management. (10 marks)
2. Write a note on the Neuropsychiatric Inventory (NPI). (5 marks)
3. Describe the management of agitation in dementia. (5 marks)
4. What are the risks of antipsychotic use in dementia? Discuss evidence-based alternatives. (10 marks)
5. Write a note on CATIE-AD study. (5 marks)

CJD

1. Describe the clinical features, investigations and management of Creutzfeldt-Jakob disease. (10 marks)
2. Compare sporadic CJD with variant CJD. (5 marks)
3. What is RT-QuIC? Describe its significance in CJD diagnosis. (5 marks)
4. Write a note on prion diseases. (5 marks)

Cognitive Assessment

1. Describe the MMSE, components and scoring. What are its limitations? (10 marks)
2. Compare MMSE with MoCA. Which is better for detecting MCI and why? (10 marks)
3. Write a note on the Clinical Dementia Rating (CDR) scale. (5 marks)
4. Describe ADAS-Cog and its role in clinical trials. (5 marks)
5. What is the MoCA? Describe its components and advantages over MMSE. (5 marks)
6. Write a note on clock drawing test. (5 marks)

MCI

1. Define Mild Cognitive Impairment. Classify and describe conversion rates. (10 marks)
2. Differentiate MCI from early Alzheimer's disease. (5 marks)
3. What is Mild Neurocognitive Disorder as per DSM-5? (5 marks)

Legal and Ethical

1. Discuss capacity assessment in a patient with dementia. (10 marks)
2. Write a note on advance directives and dementia. (5 marks)
3. Describe the ethical issues in driving cessation in dementia. (5 marks)

Caregiver

1. Describe caregiver burden in dementia, assessment and management. (10 marks)
2. Write a note on the Zarit Burden Interview. (5 marks)

SECTION 4: EXAMINER'S FAVOURITE TRAPS AND HOW TO AVOID THEM

SECTION 5: PREDICTED HIGH-PROBABILITY QUESTIONS (2026 Exam)

Almost Certain (prepare as 10-mark essays)

1. Classify dementia. Describe clinical features and management of Alzheimer's disease, include newer disease-modifying therapies.
2. Describe BPSD, classification, assessment (NPI), and evidence-based management.
3. Clinical features, diagnosis and management of DLB, differentiate from PDD.
4. Reversible dementias, with special emphasis on pseudodementia and its differentiation from true dementia.

Very Likely (prepare as 5-mark short answers + be ready for 10)

1. Normal Pressure Hydrocephalus, Hakim-Adams triad, tap test, VP shunt outcomes.
2. Behavioral variant FTD, Rascovsky criteria and management.
3. Compare MMSE and MoCA, with specific focus on MCI detection.
4. Vascular dementia, Hachinski Ischemic Score and management.
5. Biomarkers in AD, A/T/N framework, CSF, PET, blood biomarkers.
6. CJD, sporadic vs variant, EEG findings, RT-QuIC.

Watch These (may appear as short answers or viva)

1. Caregiver burden assessment and management, Zarit scale.
2. Capacity assessment in dementia, components and clinical approach.
3. Lecanemab and donanemab, mechanism, trial results, ARIA.
4. C9orf72, role in FTD and ALS.
5. Delirium superimposed on dementia, CAM criteria, management.

SECTION 6: MARKS ALLOCATION STRATEGY

For a 10-Mark Essay on Dementia

For a 5-Mark Short Answer

General Rules

• Tables score better than paragraphs, examiners scan for structure
• Start with definition, even if not asked; sets the frame
• End with a clinical pearl or management note, shows applied knowledge
• Never waste space on re-reading the question, jump to content

SECTION 7: TOPIC CROSS-LINKS

These topics frequently appear together in the same question or as sub-parts:

Analysis based on PG exams MD Psychiatry examination papers 2007-2026, PG theory papers, PG entrance patterns, and published question bank compilations.

Quick Review

VIGNETTE 1: The Professor Who Forgot His Lectures

Case:

Mr. Arvind Kulkarni, 72 years old, retired professor, is brought by his wife with a 3-year history of progressive memory difficulty. Initially he began forgetting appointments and students' names. Over the past year, he has been unable to manage his finances, gets lost in familiar neighbourhoods, and repeats the same questions within minutes. He denies any memory problems, "my wife is overreacting." There are no focal neurological signs. MMSE score: 19/30. MRI brain shows bilateral hippocampal and parietal atrophy. He has no vascular risk factors.

Q1. What is the most likely diagnosis? What specific MMSE finding pattern supports this?

Answer: Most likely diagnosis is Alzheimer's disease (Major Neurocognitive Disorder due to AD).

Supporting features: insidious onset, progressive course over 3 years, episodic memory impairment as the dominant early symptom, denial/anosognosia (patient minimises deficits, contrasts with pseudodementia), instrumental ADL impairment (finances, navigation), no vascular risk factors, MMSE 19/30 (mild-moderate range), bilateral hippocampal atrophy on MRI (medial temporal lobe atrophy, hallmark of AD).

MMSE pattern: disproportionate loss on orientation (temporal first: year/month/date before place), registration/recall (3-word recall severely impaired), with relative preservation of language tasks early.

Q2. What investigations would you order to confirm the diagnosis and exclude reversible causes?

Answer:

First-line bloods (exclude reversible): FBC, ESR, LFT, RFT, TFT (TSH), blood glucose, serum B12, folate, VDRL, HIV serology, serum calcium.

Neuroimaging: MRI brain (already done, shows MTA; Scheltens score ≥2 in bilateral hippocampus).

Neuropsychological testing: MoCA (more sensitive than MMSE for documenting profile), ACE-III (VLOM ratio to differentiate AD from FTD).

CSF biomarkers (if available/clinical trial): Aβ42↓, phospho-tau↑, total-tau↑, Aβ42/40 ratio↓, confirms AD pathology.

Amyloid PET (if available): Positive cortical amyloid uptake, confirms amyloid pathology; required for anti-amyloid therapy eligibility.

FDG-PET (if diagnosis uncertain): Bilateral temporo-parietal + posterior cingulate hypometabolism, AD pattern.

Q3. Outline the pharmacological management. What is the role of lecanemab in this patient?

Answer:

Current stage: Mild-moderate AD (MMSE 19/30), appropriate for cholinesterase inhibitor initiation.

Cholinesterase inhibitor: Donepezil 5mg OD for 4-6 weeks → titrate to 10mg OD. Alternative: rivastigmine (oral or patch) or galantamine.

Add memantine if progresses to moderate-severe stage (MMSE <15) or as combination for added benefit.

Lecanemab eligibility: Requires (a) early AD, MCI or mild dementia stage; (b) amyloid PET positive or CSF amyloid biomarkers confirming amyloid pathology; (c) MMSE ≥22 (mild stage) preferred. With MMSE 19, this patient is at the border, may qualify for mild AD criteria. Main risk: ARIA-E and ARIA-H (require baseline and surveillance MRI). APOE4 genotyping recommended pre-treatment (APOE4 homozygotes: highest ARIA risk). Benefit: 27% slowing of clinical decline (CLARITY-AD trial, 2022).

Non-pharmacological: Cognitive stimulation, structured activities, caregiver education, environmental safety modifications, driving assessment.

VIGNETTE 2: The Retired Brigadier with a "Good Day, Bad Day"

Case:

Mr. Dharamveer Singh, 74 years old, retired army officer, is brought by his son with 2-year history of fluctuating memory and attention. His son reports that some days he is completely lucid, converses normally, and recalls recent events; on other days he seems confused, stares blankly, and cannot recognise his grandchildren. Over the past year, he reports seeing "small children playing in the corner of the room", which he initially found amusing, now frightening. His wife notes he cries out during sleep and has knocked her off the bed twice while "fighting in his dreams." He has mild right-hand tremor and slowness noticed for the past 8 months. MMSE: 23/30.

Q1. What is the most likely diagnosis? Which four features point to this diagnosis?

Answer: Most likely diagnosis: Dementia with Lewy Bodies (DLB).

The four McKeith core features are all present:

1. Fluctuating cognition, good days and bad days, episodic confusion, variable alertness
2. Recurrent visual hallucinations, well-formed, detailed (small children), early in course
3. REM sleep behaviour disorder (RBD), acting out dreams, vocalisation, injuring bed partner
4. Parkinsonism, resting tremor + bradykinesia (right hand, slowness)

Per McKeith 2017 criteria: 2 of 4 core features = Probable DLB. This patient has all 4 = Probable DLB with high confidence.

Q2. His son asks about treating the visual hallucinations with haloperidol. What is your response?

Answer: Haloperidol is absolutely contraindicated in DLB.

Neuroleptic sensitivity reaction occurs in 30-50% of DLB patients exposed to conventional antipsychotics (and higher-dose atypicals). Clinical consequences: severe Parkinsonism, autonomic instability, impaired consciousness, accelerated cognitive decline, and death in severe cases.

Mechanism: DLB involves severe dopaminergic deficit (nigrostriatal) combined with profound cholinergic deficits. Blocking D2 receptors with haloperidol produces catastrophic extrapyramidal and autonomic decompensation.

Safe options for psychosis in DLB:

• Quetiapine (preferred): 12.5-25mg at night; lowest dopamine blockade among atypicals; titrate slowly
• Clozapine: 6.25-25mg; evidence from Parkinson's psychosis literature; requires regular CBC (agranulocytosis risk)
• Rivastigmine: Treatment of cognitive symptoms also reduces hallucinations (cholinergic restoration); first-line overall

First step before any antipsychotic: Trial of rivastigmine (cholinesterase inhibitor), reduces frequency and distress of hallucinations in DLB without neuroleptic sensitivity risk.

Q3. Describe the investigations you would perform to confirm the diagnosis.

Answer:

Clinical biomarkers (McKeith 2017 indicative biomarkers):

• DaTSCAN (SPECT): Reduced dopamine transporter uptake in striatum, expected to be abnormal in DLB; distinguishes DLB from AD (normal DaTSCAN)
• Cardiac MIBG scintigraphy: Reduced cardiac adrenergic uptake, abnormal in DLB/PDD; preserved in AD
• Polysomnography (PSG): Confirms REM sleep without atonia, objective confirmation of RBD

Neuroimaging:

• MRI: relative preservation of medial temporal lobe (unlike AD); generalised atrophy; no significant WMH
• FDG-PET: occipital hypometabolism (characteristic of DLB; unlike AD where occipital is spared until late)

Neuropsychological testing: Visuospatial deficits early (constructional apraxia, Rey figure), attentional fluctuation, frontal-executive deficits

EEG: Posterior slow wave activity, transient sharp waves, supportive but not diagnostic

VIGNETTE 3: The CEO Who Became Rude

Case:

Mr. Rakesh Mehta, 57 years old, successful businessman, is brought by his wife with an 18-month history of personality change. She reports that he has become "a completely different person", making offensive comments to clients, spending impulsively on unnecessary purchases, and recently exposing himself in a shopping mall. He has been eating voraciously, particularly craving sweets, and has gained 8 kg. He shows no remorse or awareness of his behaviour. Neuropsychological testing shows executive dysfunction but relatively preserved memory and visuospatial skills. MRI brain: frontal and anterior temporal atrophy bilaterally.

Q1. What is the diagnosis? List the specific diagnostic criteria met.

Answer: Diagnosis: Behavioral Variant Frontotemporal Dementia (bvFTD), Rascovsky Criteria 2011.

Features present (need 3 of 6 for POSSIBLE; neuroimaging evidence = PROBABLE):

MRI: frontal and anterior temporal atrophy = PROBABLE bvFTD

Age 57 is characteristic, bvFTD is the most common dementia in those under 65.

Q2. What is the role of genetic testing in this patient? Name the three most important genes.

Answer: Genetic testing is indicated because:

• Age of onset <65 years
• Family history (if present), autosomal dominant inheritance in ~30-40% of familial FTD
• FTD-MND co-occurrence raises C9orf72 probability significantly

Three key genes:

Swipe to compare →

Process: Genetic counselling before testing; inform about implications for first-degree relatives; predictive testing protocol for at-risk family members.

Q3. Describe the management of this patient, pharmacological and non-pharmacological.

Answer:

No disease-modifying therapy available.

Pharmacological, behavioural symptoms:

• SSRIs first-line: Sertraline 50-200mg/day or fluvoxamine 50-300mg/day, evidence for reducing disinhibition, compulsive behaviours, hyperorality, impulsive acts (open-label studies)
• Low-dose atypical antipsychotics (quetiapine 25-50mg) for severe behavioural disturbance unresponsive to SSRIs
• Avoid: Cholinesterase inhibitors (no evidence; galantamine may worsen hyperorality); memantine (conflicting, some suggest worsening)

Non-pharmacological:

• Structured daily routine, reduces compulsive behaviours through predictability
• Redirection techniques for disinhibited behaviour
• Environmental safety, financial power of attorney urgently (before capacity is fully lost); remove credit cards, car keys
• Staff and family training: explain empathy impairment; de-personalise the behaviour
• Occupational therapy for meaningful activity

Legal/social urgency: At 57, capacity may still be partially present, urgent advance care planning, lasting power of attorney for finances and health, will review. His business and financial affairs are at high risk from impulsive decisions.

VIGNETTE 4: The Triad That Points to a Treatable Diagnosis

Case:

Mrs. Kamala Iyer, 70 years old, retired teacher, is brought with a 1-year history of progressive gait difficulty, urinary urgency with occasional incontinence, and gradual cognitive decline. Her daughter notes she walks with short, shuffling steps and takes a long time to "get going" from a chair. Neurological examination: wide-based gait, no tremor, no rigidity at rest, arm swing preserved. She has no history of hypertension, diabetes, or head injury. CT brain shows disproportionately enlarged lateral ventricles with an Evans index of 0.34, and the cortical sulci over the vertex appear effaced. Lumbar puncture opening pressure: 160 mm H2O.

Q1. What is the diagnosis? What findings confirm it?

Answer: Diagnosis: Idiopathic Normal Pressure Hydrocephalus (iNPH), Hakim-Adams syndrome.

Confirming findings:

• Clinical triad: Gait apraxia (magnetic gait, wide-based, short steps, difficulty initiating) + urinary incontinence (urge type) + cognitive decline (frontal-subcortical pattern), appearing in the classic G-I-D sequence
• CT findings: Evans index 0.34 (>0.3 confirms ventriculomegaly) + effaced sulci over the vertex (disproportionate, ventricles enlarged but convexity sulci small = DESH pattern)
• LP opening pressure: 160 mm H2O = NORMAL (<200 mm H2O), defining criterion: large ventricles with normal pressure
• Gait characteristics: Magnetic gait with preserved arm swing and no resting tremor, distinguishes from Parkinson's disease

Q2. What is the CSF tap test? How does it help?

Answer: The CSF Tap Test (Miller Fisher Test):

Procedure: Lumbar puncture with removal of 30-50 mL of CSF; gait and cognitive function assessed before and at 1 hour, 24 hours, and 72 hours post-tap.

Positive result: Objective improvement in gait (shorter step time, wider step length, increased gait velocity on timed tests) within 24-72 hours.

Diagnostic value:

• Sensitivity: ~50-60%
• Specificity: ~80-90%
• A positive tap test strongly predicts good shunting outcome (PPV ~75-90%)
• A negative tap test does not exclude NPH (false negative rate ~40-50%)

Extended lumbar drain (if tap test negative but clinical suspicion high):

• 3-5 days continuous CSF drainage via external lumbar drain (~150-200 mL/day)
• Higher sensitivity than single tap test (~70-80%)
• Cumbersome but more predictive

Q3. Describe the surgical treatment and expected outcomes.

Answer:

Ventriculoperitoneal (VP) Shunt:

• Catheter placed in lateral ventricle → peritoneal cavity
• Uses a pressure-adjustable (programmable) valve, allows non-invasive pressure setting post-operatively
• General anaesthesia required

Predictors of good outcome:

• Young age (relative)
• Short symptom duration (<2 years)
• Gait-predominant presentation (vs dementia-predominant)
• Positive CSF tap test
• No significant comorbid white matter disease

Expected response rates:

Complications:

• Over-drainage → subdural haematoma (use programmable valve to adjust)
• Shunt infection (~5%)
• Shunt failure/malfunction (requires revision)
• Intracranial haemorrhage (insertion-related)

VIGNETTE 5: The Widow Who "Can't Remember Anything"

Case:

Mrs. Sujata Patel, 65 years old, retired bank manager, is brought by her son 6 months after her husband's death. She reports severe memory difficulty, inability to concentrate, poor sleep, and loss of appetite. She scores 21/30 on MMSE. She volunteers extensively during testing: "I can't do this, I've forgotten everything, I'm useless." On formal testing, her performance is inconsistent, she scores 0/3 on word recall in one trial but 3/3 in another. She has a previous history of depression 10 years ago, resolved with antidepressants. MRI brain: no significant atrophy.

Q1. What is the most likely diagnosis and how does it differ from true dementia?

Answer: Most likely diagnosis: Depressive Pseudodementia (Depressive Pseudodementia, Kiloh 1961), now conceptualised as a major depressive episode with prominent cognitive symptoms.

Features supporting pseudodementia over true dementia:

True dementia features absent: no anosognosia, no consistent deficits, no pattern-specific neuropsychological loss, no structural changes.

Q2. What investigations would help differentiate, and what is your management plan?

Answer:

Investigations to differentiate:

Management:

1. Antidepressant: Escitalopram 5-10mg OD (or sertraline 50mg OD), first-line for elderly depression
2. Mirtazapine 15-30mg if insomnia + poor appetite prominent (sedating, orexigenic)
3. Psychotherapy: Grief-focused CBT; behavioural activation; interpersonal therapy
4. Monitor cognition: Formal MoCA at 3 months, should improve with depression remission
5. ECT: If severe, refractory, or rapid functional decline, also diagnostically confirmatory if cognitive improvement occurs

Caution: 15-20% of pseudodementia patients convert to true dementia within 3 years, follow-up neuropsychological assessment at 12 months essential.

Q3. What is the significance of this diagnosis for long-term prognosis?

Answer:

• Pseudodementia is not entirely benign despite being "reversible"
• 15-20% conversion rate to true dementia (usually AD) within 3 years
• Cognitive deficits may not fully resolve, residual cognitive impairment (especially processing speed and memory) in 30-40%
• Depression itself is a risk factor for dementia (proposed mechanisms: HPA dysregulation, neuroinflammation, hippocampal volume loss from glucocorticoid toxicity)
• Long-term: depression is both a prodrome AND a risk factor for AD
• Follow-up: Annual neuropsychological review for 3-5 years; monitor for emerging dementia features despite depression treatment

VIGNETTE 6: The Young Man with Rapidly Progressive Confusion

Case:

Mr. Pradeep Kulkarni, 62 years old, previously healthy, presents to neurology with a 6-week history of rapidly worsening confusion, unsteadiness, and abnormal jerking movements of his limbs. His wife reports the confusion began 2 months ago but has progressed alarmingly. On examination: marked cognitive impairment, cerebellar ataxia, stimulus-sensitive myoclonus, and extrapyramidal signs. MMSE: 12/30 (dropped from normal 2 months ago). EEG shows periodic sharp wave complexes at approximately 1.5 Hz. MRI brain (DWI): cortical ribboning with restricted diffusion in the cortex and basal ganglia.

Q1. What is the diagnosis and what investigations confirm it?

Answer: Diagnosis: Sporadic Creutzfeldt-Jakob Disease (sCJD).

Diagnostic criteria met (WHO Probable sCJD):

• Rapidly progressive dementia (6 weeks from normal to MMSE 12), hallmark
• Myoclonus, stimulus-sensitive, present, one of the core features
• Cerebellar ataxia, present
• EEG: Periodic sharp wave complexes (PSWC) at 1-2 Hz, pathognomonic for sCJD
• MRI (DWI): Cortical ribboning + basal ganglia DWI restriction, characteristic pattern

Confirmatory investigations:

Q2. How would you distinguish this from variant CJD?

Answer:

Q3. What management would you institute and what infection control measures are required?

Answer:

No disease-modifying treatment. CJD is uniformly fatal. Management is entirely palliative and supportive.

Symptom management:

• Clonazepam 0.5-2mg TDS, for myoclonus
• Opioids (morphine), for pain and distress in late stages
• Antidepressants if mood symptoms in prodrome
• Nasogastric/PEG feeding consideration: ethically complex; family discussion required

Palliative care:

• Early hospice referral
• Anticipatory prescribing (myoclonus, agitation, pain)
• Family counselling: anticipatory grief, what to expect (akinetic mutism, death 5-6 months)
• Psychological support for family: genetic implications if familial variant suspected

Infection control (critical):

• CJD is a notifiable disease in India
• Standard universal precautions for healthcare workers (gloves, gown)
• Prions are resistant to standard sterilisation, specific decontamination required:
• Surgical instruments: extended autoclave at 134°C for 18 minutes OR immersion in 1M NaOH for 1 hour
• Single-use instruments preferred for all invasive procedures
• Corneal, dura mater, and tissue donations are absolutely contraindicated
• Autopsy: specialist neuropathology centre only, with enhanced PPE
• Genetic testing (PRNP): only if familial CJD suspected; genetic counselling mandatory first

VIGNETTE 7: Post-Stroke Forgetfulness

Case:

Mr. Ashok Rao, 68 years old, hypertensive, diabetic, smoker (40 pack-years), presents with cognitive decline that his son describes as "step-by-step worsening, not gradual." He had a stroke 2 years ago with full motor recovery, then a TIA 8 months ago. After each event, his memory and executive function dropped and never fully recovered. He has dysarthria, brisk reflexes, and a positive snout reflex. MRI brain: multiple lacunar infarcts in basal ganglia and thalamus, periventricular white matter hyperintensities (Fazekas 3). Hachinski score: 9.

Q1. Diagnose and classify this patient's dementia type.

Answer: Diagnosis: Vascular Dementia (VaD), most likely Multi-infarct dementia with subcortical component.

Classification:

• Multi-infarct type: Multiple strokes with stepwise deterioration pattern
• Subcortical ischaemic VaD component: Lacunar infarcts in basal ganglia/thalamus + periventricular WMH (Fazekas 3), subcortical white matter disease pattern

Supporting evidence:

• Hachinski score 9 (≥7 = VaD)
• Stepwise deterioration (not gradual as in AD)
• Clear temporal relationship between cerebrovascular events and cognitive steps
• Multiple vascular risk factors (HTN, DM, smoking)
• MRI: lacunar infarcts + periventricular WMH
• Neurological signs: dysarthria, brisk reflexes, snout reflex (pseudobulbar features, subcortical)

Q2. What are the principles of management?

Answer:

Secondary vascular prevention (most important):

• Antiplatelet therapy: Aspirin 75-150mg OR clopidogrel 75mg daily (if aspirin intolerant); dual antiplatelet briefly post-TIA then single agent
• BP control: Target <130/80 mmHg, ACE inhibitor or ARB preferred (ramipril, perindopril have RCT evidence for dementia prevention in vascular disease)
• Statin therapy: Atorvastatin 40-80mg, LDL <70 mg/dL target
• Glycaemic control: HbA1c <7% (individualise)
• Smoking cessation: Immediately; reduces further vascular events by 50%
• Anticoagulation: If AF present (warfarin or DOAC), not antiplatelet

Symptomatic treatment for cognition:

• ChEIs (donepezil): modest evidence in VaD; some guidelines recommend
• Memantine: some evidence; particularly for subcortical VaD
• No disease-modifying therapy specific to VaD

Neuropsychiatric symptoms:

• Post-stroke depression: SSRIs (sertraline); very common, must screen actively
• Emotional lability (pseudobulbar affect): SSRIs or very low dose TCAs

Q3. What is the Hachinski Ischemic Score and how is it calculated in this patient?

Answer:

The Hachinski Ischemic Score (HIS) was developed to clinically differentiate vascular dementia from Alzheimer's disease based on clinical features (Hachinski et al., 1975). Maximum score = 18.

Calculation for this patient:

Score ≥7 = VaD (this patient scores well above threshold).

VIGNETTE 8: The Man Who Lost His Words

Case:

Mr. Venkatesh Iyer, 61 years old, retired journalist, is referred by a speech therapist with a 2-year history of progressive language difficulty. He can no longer name common objects, "that thing you use for...", and struggles to understand words. His vocabulary has shrunk remarkably. However, his memory for day-to-day events is intact, he remembers what he had for lunch, his appointments, and recent news. His face recognition is also impaired. MRI shows asymmetric left anterior temporal lobe atrophy.

Q1. Identify the syndrome and its FTD subtype.

Answer: Syndrome: Semantic Variant Primary Progressive Aphasia (svPPA), also called Semantic Dementia.

Key features:

This is one of the three FTD clinical syndromes:

1. bvFTD, behavioural and personality changes (frontal)
2. svPPA (this case), semantic loss (left anterior temporal)
3. nfvPPA, effortful, agrammatic speech (posterior frontal/insula)

Q2. How does this differ from progressive non-fluent aphasia (nfvPPA)?

Answer:

Q3. What is the management approach and prognosis?

Answer:

No disease-modifying therapy.

Speech-Language Therapy (central):

• Semantic knowledge exercises, slow the rate of vocabulary loss
• Communication aids, picture boards, AAC (Augmentative and Alternative Communication) devices
• Caregiver training in communication strategies

Cognitive rehabilitation:

• Naming therapy (relearning word-picture associations), modest short-term benefit
• Personalised vocabulary maintenance

Behavioural symptoms (if present):

• As disease progresses, svPPA may develop bvFTD features (right temporal involvement, or spread to frontal)
• SSRIs for any emerging disinhibition or compulsive behaviours

Prognosis:

• svPPA has relatively slower progression than bvFTD
• Median survival from symptom onset: ~8-12 years (longer than bvFTD at 6-8 years)
• Language deterioration → mutism → late global cognitive decline
• Personality and social cognition remain relatively preserved until late (then may develop FTD features)

VIGNETTE 9: Delirium on Dementia

Case:

Mr. Gajanan Deshmukh, 78 years old, known case of mild AD (MMSE 22, on donepezil 10mg), is admitted to medicine ward for a urinary tract infection. Over the next 24 hours, his son notices an acute change, he is seeing insects on the ceiling, cannot recognise his son, is pulling out his IV line, and shouting. He was lucid when admitted. Nursing staff ask the resident to prescribe "something to calm him down quickly."

Q1. What is the diagnosis and what features distinguish it from his baseline dementia?

Answer: Diagnosis: Delirium Superimposed on Dementia (DSD).

Distinguishing DSD from baseline dementia:

CAM (Confusion Assessment Method), met:

1. Acute onset and fluctuating course, YES
2. Inattention, YES
3. Disorganised thinking, YES
4. Altered level of consciousness, YES

(Need 1+2 and either 3 or 4)

Dementia is the single biggest risk factor for delirium, 2-5x increased risk. DSD worsens long-term dementia trajectory.

Q2. What is the immediate management priority?

Answer:

Step 1, Identify and treat the precipitant (most important):

• Treat UTI: appropriate antibiotics (urine culture and sensitivity; empirical if septic)
• Other precipitant checklist: pain (unrecognised), constipation, urinary retention, dehydration, electrolyte imbalance, medication toxicity (new drugs?), hypoxia, hypoglycaemia

Step 2, Non-pharmacological interventions (first-line):

• Reorientation: gentle, repeated, familiar faces and voices
• Lighting: bright light in daytime, dim at night, circadian cues
• Familiar objects from home
• Early mobilisation (sit out of bed if clinically safe)
• Restore sensory aids: hearing aids, glasses
• Maintain hydration and nutrition
• Minimise invasive monitoring/lines

Step 3, Pharmacological (only if safety risk or severe distress):

• Low-dose haloperidol 0.25-0.5mg oral/IM, cautiously (NOT first-line; only if non-pharm fails and risk to self/others)
• Avoid benzodiazepines as first-line, worsen confusion, increase fall risk, paradoxical agitation
• Note: This patient has AD, donepezil may continue (cholinergic support may help)
• If DLB were the underlying dementia: NEVER haloperidol, neuroleptic sensitivity (although this case is AD, awareness of the DLB caution is essential)

Q3. What is the prognosis of delirium superimposed on dementia?

Answer:

DSD has a significantly worse prognosis than delirium in non-demented individuals:

• Higher mortality (in-hospital and 6-month) compared to delirium alone or dementia alone
• Accelerated cognitive decline, each episode of DSD associated with faster progression of underlying dementia
• Incomplete resolution, cognitive function often does not return fully to pre-delirium baseline (step-down effect)
• Increased institutionalisation, DSD episodes are major triggers for nursing home placement
• Caregiver impact, acute behavioural disturbance during DSD episodes is highly distressing and often precipitates carer breakdown

Preventive strategy (HELP, Hospital Elder Life Program):

• Proactive delirium prevention: mobility, hydration, cognitive engagement, sleep protocol, sensory aid maintenance
• Delirium is largely preventable (30-40% reduction with HELP protocol)
• For this patient: family education on DSD risk; delirium care plan documented for future admissions

VIGNETTE 10: APOE4 Positive Result

Case:

Ms. Ananya Sharma, 42 years old, software engineer, attends a genetics clinic. Her mother was diagnosed with AD at age 62, and her maternal grandmother also had dementia. She underwent a direct-to-consumer genetic test and is told she is homozygous APOE4/APOE4. She is extremely anxious and asks: "Does this mean I will definitely get Alzheimer's? Should I start medications now? Should I do a PET scan?"

Q1. How do you interpret her APOE4 homozygous result?

Answer:

APOE4 is a risk factor, NOT a deterministic mutation.

Key counselling points:

• APOE4/4 does NOT guarantee AD, 40-50% of APOE4 homozygotes do not develop AD
• APOE4 lowers mean age of onset by ~7-10 years per allele
• It is not a Mendelian dominant mutation like PSEN1, no deterministic inheritance
• Unlike BRCA1, APOE4 does not trigger surveillance protocols or preventive surgery
• She should NOT be treated as a patient, she is currently cognitively normal at age 42

Q2. Should she start cholinesterase inhibitors or undergo amyloid PET now?

Answer:

No, neither is currently indicated.

Cholinesterase inhibitors:

• Indicated for symptomatic dementia or MCI with documented cognitive decline
• No evidence of benefit in cognitively normal individuals, even high-risk ones
• Potential harms: side effects without benefit; psychological impact of treating a well person as a patient

Amyloid PET:

• No current clinical indication in asymptomatic individuals, even APOE4 homozygotes
• Being used in RESEARCH settings (A4 trial, AHEAD 3-45 trial), but these are research studies
• Positive amyloid PET in a cognitively normal person = "Alzheimer's pathological change", but does NOT mean she will develop dementia, and no treatment is currently approved to act on this
• Potential harms: anxiety, insurance implications, no actionable treatment decision

What IS recommended:

• Cognitive baseline assessment (MoCA, neuropsychological battery), to document baseline for future comparison
• Vascular risk factor optimisation (most modifiable: BP, DM, lipids, smoking, exercise, sleep, hearing)
• Lifestyle interventions: aerobic exercise (strongest evidence for risk reduction), Mediterranean diet, social engagement, cognitive activity
• Annual follow-up with neuropsychological testing from age ~50
• Clinical trial enrolment (AHEAD 3-45 or similar, testing lecanemab in preclinical AD in APOE4 carriers)
• Psychological support: genetic counselling for anxiety management

Q3. What genetic counselling principles apply to this case?

Answer:

Key principles:

1. Non-directive counselling: Counsellor presents information objectively; patient makes their own decisions about testing, surveillance, disclosure
2. Pre-test counselling: Should have occurred before the direct-to-consumer test, she bypassed this (a limitation of DTC testing)
3. Implications for family members: Her children each have a 50% chance of inheriting one APOE4 allele (she is 4/4; any children will receive one 4); her siblings should be informed of the possibility
4. Insurance discrimination: APOE4 results should be treated as sensitive; potential implications for life/health insurance in some jurisdictions
5. Psychosocial impact: APOE4/4 result generates significant anxiety; psychological support and follow-up essential; anxiety itself may impair cognitive performance (ruling out performance anxiety on baseline tests)
6. Right not to know: Apply to siblings and children, they have the right not to know their own APOE status
7. Distinguish from PSEN1/PSEN2/APP: Those ARE deterministic mutations; APOE4 is NOT, counselling language must reflect this clearly

VIGNETTE 11: Capacity to Make a Will

Case:

Mr. Ramchandra Kulkarni, 80 years old, with mild-to-moderate AD (MMSE 18/30, CDR 1), wishes to update his will to exclude one of his four children. His solicitor contacts the attending psychiatrist for a formal assessment of testamentary capacity.

Q1. Define testamentary capacity and describe its four legal components.

Answer:

Testamentary capacity is the legal and psychiatric determination that a person has sufficient mental capacity to make a valid will at the time of execution.

It was defined in the legal case Banks v Goodfellow (1870), which established four criteria. A testator (person making a will) must:

Key legal principle (Banks v Goodfellow): A person can have a diagnosis of dementia AND still have testamentary capacity for a specific will, if the above criteria are met. Capacity is decision-specific.

Q2. How would you conduct the capacity assessment?

Answer:

Formal structured assessment:

1. Review records: Current cognitive test scores (MMSE 18, mild-moderate); neuropsychological profile; current medication; recent clinical notes

1. Interview patient alone (and separately with informant):
2. Apply the four Banks v Goodfellow criteria above
3. Explore: Does he know all four children? Can he name them? Does he understand what the will does? Can he articulate why he wishes to exclude this child, is the reason rational and his own, or delusional?

1. Assess for delusions (critical):
2. The most common issue is a persecutory or theft delusion about the excluded child
3. If he believes the child "is stealing from him" based on a theft delusion (common in AD) → this delusion may be poisoning his judgment → capacity for THIS decision = compromised
4. If he has a clear, rational, non-delusional explanation (e.g., "this child never visits, we have been estranged for 30 years") → delusion-free, rational decision → capacity may be intact

1. Document thoroughly: Time, date, verbatim responses, clinical reasoning, conclusion

1. Outcome: If capacity intact → sign capacity certificate supporting will execution. If impaired → advise solicitor; may need Court of Protection/Guardian involvement

Q3. What are the broader ethical and legal issues in dementia and capacity?

Answer:

• Driving: Mild AD, requires on-road assessment. Moderate AD, generally unsafe. India has no mandatory reporting law currently; clinician has duty to advise strongly
• Financial decisions: Complex financial decisions require higher capacity than simple ones; power of attorney should be executed while capacity is present
• Treatment decisions: Each medical decision assessed individually; a patient who cannot manage finances may still have capacity to consent to a tooth extraction
• Advance Directives (MHA 2017): Valid in India; allow future treatment/refusal instructions; nominated representative can be appointed
• Elder abuse: Higher in dementia, financial exploitation most common; duty to report if suspected
• Research participation: Higher ethical bar, independent ethics review, family/representative consent alongside patient assent

VIGNETTE 12: The Caregiver Who Is Breaking Down

Case:

Mrs. Kamini Iyer, 68 years old, has been caring for her husband with moderate AD (MMSE 14/30, BPSD prominent, wandering at night, delusions, aggressive behaviour) for 4 years. She attends clinic alone. She is tearful throughout, reports sleep deprivation for months ("he keeps getting up at night"), has stopped meeting friends entirely, and has lost 5 kg over 3 months. She says "I don't want to put him in a home, I promised I wouldn't." Zarit Burden Interview score: 54/88.

Q1. Assess caregiver burden in this case, what does the Zarit score indicate?

Answer:

Zarit Burden Interview (ZBI): 22-item self-report scale assessing subjective caregiver burden across physical, emotional, social, and financial domains. Each item rated 0-4; total range 0-88.

Score interpretation:

Mrs. Iyer's score: 54 = Moderate to severe burden

Clinical manifestations of burden present:

• Physical: Sleep deprivation, weight loss (5 kg), exhaustion
• Psychological: Tearfulness, social withdrawal, high distress
• Social: Complete social isolation (stopped meeting friends)
• Role entrapment: Feeling unable to leave ("I promised")
• Bereavement: Anticipatory grief, her husband is present but psychologically "gone"

This caregiver is at high risk of developing major depression (50-70% of dementia caregivers develop depression) and medical complications from neglect of her own health.

Q2. What interventions would you recommend for her?

Answer:

Multi-level caregiver support:

1. Psychoeducation (immediate priority):

• Dementia course and prognosis, what to expect; planning ahead
• BPSD explanation, "he cannot control this behaviour; the disease controls him"
• Practical guidance: managing nocturnal wandering (locks, door alarms, safe spaces), managing aggression (de-escalation, not confrontation)

2. Practical/Environmental:

• Sleep hygiene for patient: Melatonin 5-10mg (reduce nocturnal waking); bright light therapy in daytime; structured activity to increase daytime activity → improve night sleep
• Door alarms, GPS tracking devices (wandering safety)
• Daycare centre attendance, gives her 8 hours of respite daily

3. Formal support:

• Respite care: Discuss day program + periodic in-patient respite (2-4 weeks/year)
• ARDSI (Alzheimer's and Related Disorders Society of India), caregiver support groups, helpline, resource connection
• Home nursing support for personal care (bathing, medications)

4. Psychological support for her:

• Grief counselling, normalise anticipatory mourning
• Challenge the "promise", explore meaning, reframe care options as expressions of love not betrayal
• Individual CBT or supportive therapy for depressive features
• Screen formally for depression (PHQ-9 or HDRS), she may need antidepressant treatment
• Peer support group (other dementia caregivers), powerful validation

5. Financial counselling:

• Benefits available (government schemes for elderly and disability in India)
• Long-term financial planning

Q3. When would institutionalisation be appropriate to discuss, and how would you approach this conversation?

Answer:

Indicators that institutionalisation should be actively discussed:

Approach to the conversation:

1. Acknowledge the promise: "I understand this was a commitment that came from love."
2. Reframe: "The promise was to care for him. Placing him in a facility where he gets 24-hour specialised care while you can visit daily and be his wife, not his nurse, may be the most caring thing you can do."
3. Address guilt: Normalise; explain caregiver health is also patient's welfare
4. Explore options: Memory care units vs nursing homes vs respite care as step before permanent placement
5. Involve family: Other children should share decision, reduce burden on her alone
6. No rush: This is a process conversation; she needs time; revisit at next appointment
7. Practical visit: Arrange a visit to a memory care facility before deciding

All patient names in this document are fictitious. Sources: Kaplan & Sadock's Synopsis of Psychiatry 12th Ed, Oxford Textbook of Psychiatry 6th Ed, Cummings' Neuropsychiatry and Behavioral Neuroscience 3rd Ed, DSM-5, ICD-11, McKeith 2017, Rascovsky 2011, NIA-AA 2018