ICD-10 requires: (1) Decline in memory and learning; (2) Decline in other cognitive abilities (judgment, thinking, general processing); (3) Duration > 6 months; (4) Impaired performance in daily living; (5) Clear consciousness ^[1]

ICD-10 codes: F00 (AD), F01 (Vascular dementia), F02 (Dementia in other diseases — Pick's, CJD, Parkinson's, Huntington's, HIV), F03 (Unspecified)

MCI: Subjective + Objective cognitive impairment without significant functional impairment. Intermediate stage between normal aging and dementia. Not all patients with MCI will progress to dementia. ^[1]

Why the amnestic vs non-amnestic distinction matters: Amnestic MCI (memory-predominant) has the highest conversion rate to AD. Non-amnestic MCI may progress to FTD or DLB instead.

Over 80% of dementia patients have BPSD. Delusions 60%, Affective symptoms 40%, Anxiety 35%, Verbal outburst 33%, Hallucination 20%, Aggression 13%. ^[1]

Two categories:

• Observed behaviours: screaming, restlessness, wandering, aggression, agitation, culturally inappropriate behaviour
• Elicited psychological symptoms: depression, anxiety, hallucination, delusion

Why BPSD matters:

• It is the main driver of caregiver stress
• It is the main reason for institutionalization
• It is a common exam topic — how to manage BPSD

Over 30 million people worldwide. 6–10% over 65 in North America. 9.1% prevalence in Hong Kong. "Milder" cognitive impairment 3–23%. Huge burdens to societies by 2050. ^[1]

1. Alzheimer's Disease (most common); 2. Vascular Dementia; 3. Dementia with Lewy Bodies. Mixed dementia usually means AD mixed with vascular. ^[1]

The lecture lists: Degenerative (AD, FTD, DLB), Endocrine, Mass lesion, Nutritional, Traumatic, Infectious, Autoimmune, Vascular.

Reversible causes ("DEMENTIA" mnemonic from Maksim notes) ^[2]:

~50–60% of all dementia cases. Prevalence increases with age: 10% at 65, 25% at 85. Early onset ( < 65 yo) vs late onset (≥ 65 yo). Duration: diagnosis to death 8–10 years. ^[1]

Risk factors:

• Genetics: PS1, PS2, APP (autosomal dominant, early onset); ApoE ε4 (risk factor for late onset)
• Female sex
• Family history
• Head trauma
• Low education
• Cardiovascular dysfunction (hypertension, diabetes, smoking)

1. Deposition of beta-amyloid peptides/amyloid plaques (extracellular) — Amyloid Cascade Hypothesis. 2. Formation of hyper-phosphorylated tau — Neurofibrillary Tangles (NFTs) (intracellular). 3. AD pathology usually involves the temporal lobe first, affecting hippocampus → memory impairment. 4. Cholinergic deficit: loss of cholinergic biosynthetic machinery, loss of basal forebrain cholinergic neurons → impairment of memory and attention. ^[1]

Understanding the pathology from first principles:

1. Amyloid Cascade Hypothesis: Amyloid Precursor Protein (APP) is a normal transmembrane protein. It can be cleaved by α-secretase (non-amyloidogenic, normal pathway) or by β- and γ-secretase (amyloidogenic pathway). The amyloidogenic pathway produces Aβ peptides (Aβ1-40 and Aβ1-42). Aβ1-42 is more prone to aggregation → oligomers → amyloid plaques → neurotoxicity → neuronal death.

2. Neurofibrillary Tangles (NFTs): Tau is a microtubule-associated protein that normally stabilizes axonal microtubules. In AD, tau becomes hyperphosphorylated → detaches from microtubules → aggregates into paired helical filaments → NFTs → disrupts axonal transport → neuronal death.

NFT expression needed for Aβ toxicity. NFT correlates with AD severity. NFT load higher in patients with ApoE4. Not specific for AD. Tauopathies share common end point. ^[1]

3. Temporal lobe predilection: The entorhinal cortex and hippocampus are affected earliest. This explains why short-term memory is the earliest and most prominent deficit in AD.

4. Cholinergic deficit: The nucleus basalis of Meynert (basal forebrain) provides cholinergic innervation to the cortex. In AD, these neurons degenerate → decreased acetylcholine → impaired memory and attention. This is the basis for cholinesterase inhibitor therapy.

The amyloid cascade timeline (from lecture slide): β-amyloid deposition begins decades before clinical symptoms (age 30-40), followed by microglial activation, then NFTs, then neuronal loss/neurochemical changes, and finally clinical dementia (age 70-90). ^[1]

The lecture shows imaging of hippocampal atrophy — the hallmark structural finding on MRI in AD. Medial temporal lobe atrophy (MTA) scoring on coronal MRI is used clinically.

AD Diagnosis requires: Patient history (collaterals very important), Physical examination, Neuropsychological tests, Blood tests: CBC, L/RFT, BG, TSH, B12, folate, VDRL; ECG, CXR, EEG (in specific case); Neuroimaging (CT, MRI; non-essential: PET, SPECT); CSF (total tau, phosphorylated tau, amyloid-beta) — seldom done in HK clinical setting. ^[1]

Why each investigation:

Mnemonic for basic bloods (from Ryan Ho): I (FOR)GET ABC — Imaging, Glucose, Electrolytes, Thyroid, Anaemia, B12/folate, Calcium ^[4]

"Definite": dementia with AD histopathology (post-mortem). "Probable": dementia demonstrated by clinical examination and neuropsychological testing, absence of other brain diseases. "Possible": dementia present but not typical AD presentation. ^[1]

In clinical practice, most diagnoses are "probable AD." "Definite" requires histopathological confirmation (autopsy).

Cognitive stimulation, Cognitive training, Cognitive rehabilitation, Exercise ^[1]

• Cognitive stimulation: Group activities involving discussion, reminiscence, games — evidence shows modest benefit for cognition and quality of life
• Cognitive training: Practising specific cognitive tasks (computer-based or otherwise)
• Cognitive rehabilitation: Individualized goals, compensatory strategies (calendars, reminders)
• Exercise: Aerobic exercise may slow cognitive decline and improve mood

1. Acetylcholinesterase Inhibitor (AChEI) — donepezil, rivastigmine, galantamine — for mild to moderate AD. Compensates cholinergic deficit. 2. Memantine — for moderate to severe AD — NMDA receptor antagonist. Neuroprotective and disease-modifying in theory. ^[1]

The lecture slide shows the natural history of AD from normal aging → amnestic MCI → mild dementia → loss of functional independence → behavioural symptoms → nursing home → severe stage. Drug mapping: AChEI from MCI through moderate stage; Antidepressants for early mood symptoms; Memantine from moderate stage; Atypical neuroleptics for BPSD in moderate-severe stages. ^[1]

Human monoclonal antibody selectively targeting aggregated Aβ. FDA approved 2021 (EMERGE and ENGAGE trials). Monthly IV infusions. First treatment directed at amyloid beta plaques. Risk: Amyloid-Related Imaging Abnormalities (ARIA) — brain swelling and bleeding. Monitoring: MRIs before, during titration, and with symptoms of ARIA. Effectiveness still under debate. ^[1]

Why this is important for exams: This represents a paradigm shift from symptomatic treatment to disease-modifying therapy targeting amyloid. However, the clinical benefit was modest and controversial (one trial positive, one negative). It highlights the amyloid cascade hypothesis in practice. Similar drugs: lecanemab (approved 2023), donanemab.

Step 1: Exclude physical illness potentially precipitating BPSD. Step 2: Non-pharmacological approaches — behaviour modifications, environmental modifications. Step 3: Medications — AChEI/memantine, antipsychotic, antidepressant, other neuroleptics. KEY: Keep lowest dose and shortest period if possible. Don't prescribe medications unless significant BPSD. ^[1]

Why exclude physical illness first? — A patient with dementia who becomes acutely agitated may have superimposed delirium from UTI, constipation, pain, or medication side effects. Treating the underlying cause is more effective and safer than adding psychotropics.

Non-pharmacological approaches for BPSD:

• Identify triggers (time of day, environment, hunger, pain)
• Maintain routine, reduce overstimulation
• Redirection, distraction
• Music therapy, aromatherapy, pet therapy
• Environmental modifications: adequate lighting, familiar objects, safety features

When medications are needed:

• Atypical antipsychotics (risperidone, quetiapine) at low doses for severe aggression/psychosis
• SSRIs for depressive/anxious BPSD
• Avoid typical antipsychotics (haloperidol) in DLB — pronounced sensitivity to antipsychotic EPSE ^[2][3]
• Benzodiazepines generally avoided (worsen confusion, increase fall risk)

• Covers similar content from a geriatrician's perspective (Dr. Shea Yat Fung, QMH)
• Mentions topics not covered in the primary lecture: Advanced directives, advanced care planning, feeding issues

• AChEI side effects (bradycardia, GI) are important in the context of polypharmacy
• Beers criteria / STOPP criteria — review medications that may worsen cognition (anticholinergics, benzodiazepines, antihistamines)

• Same lecturer — practical tips for psychogeriatric interviews
• Content of psychiatric history and mental state examination in elderly patients
• Emphasizes: purpose of history taking, collateral informant, mental state examination technique

• Dementia assessment is a key component of CGA
• Multidisciplinary team: geriatrician, psychiatrist, nurse, OT, PT, MSW, speech therapist

Stem: "A 69-year-old woman visited your clinic for the first time complaining of memory loss. She stated that her memory has been declining gradually for the 'past 3 or 4 years'. She also mentioned that she had trouble using appliances as she used to, and that she had forgotten how to comb her hair several times, which frightened her greatly. There was no family history of 'being senile'. Physical examination and laboratory investigations were essentially normal except for a blood pressure of 145/92 mmHg and a triglycerides level of 140 mg/dl."

Answer: G. Late-onset Alzheimer's disease

Rationale: Gradual decline over 3–4 years (insidious), memory loss + apraxia (can't use appliances, can't comb hair), age 69 (≥ 65 = late onset), normal labs except for cardiovascular risk factors. Classic AD presentation. Not early-onset (age ≥ 65). Not VaD (no stepwise decline, no stroke history). Not MCI (has functional impairment — can't do IADL).

Stem: "A 65-year-old man attended his first visit at your clinic with his wife. His wife told you that her husband had become 'a different person'. She thought that he must be upset about something because he seemed 'not to care about his appearance anymore' and that he 'swore using dirty words'. She had become 'too embarrassed to go to gatherings with him' because of his inappropriateness. The Mental Status Examination revealed an apathic, oriented man with mild memory deficits and he was easily distracted."

Answer: D. Frontotemporal dementia

Rationale: Personality and behavioural changes (disinhibition, apathy, loss of social decorum) with relatively mild memory deficits — hallmark of behavioural variant FTD. Age 65 is also compatible (FTD more common in younger-onset dementia). Not AD (behavioural > memory). Not DLB (no parkinsonism, no visual hallucinations).

Stem: "Which of the following is counted as an instrumental activity of daily living? A. Bathing B. Eating C. Preparing meals D. Toileting"

Answer: C. Preparing meals

Rationale: Bathing, eating, and toileting are all BADLs. Preparing meals is an IADL (along with finance, transportation, shopping, medications).

Stem: "Which of the following psychiatric conditions can mimic dementia and is known as 'pseudodementia' in a geriatric patient? A. Depressive disorder B. Manic episode C. Post-traumatic stress disorder D. Schizophrenia"

Answer: A. Depressive disorder

Rationale: Depression in the elderly can present with cognitive impairment (poor concentration, psychomotor slowing, memory complaints) that mimics dementia — termed "pseudodementia." This is reversible with appropriate antidepressant treatment.

Stem: "Mrs. Chan is an 87-year-old lady with early dementia. She had informed one of the clinical teams that she wished for 'do-not-attempt cardiopulmonary resuscitation (DNACPR)' when it comes to the end-of-life. However, there was no remark of 'Do not resuscitate (DNR)' in her patient record. One day she arrived at the A&E due to cardiac arrest and you are the doctor on duty. Her family insisted that you should perform CPR on her. (a) With reference to ethical principles, list two arguments for and two arguments against commencing resuscitation. (b) What would you do? Justify your answer."

Markscheme:

• For CPR: Autonomy (family's wishes may represent patient's change of mind), Beneficence (CPR may save life), No documented DNR (legally, default is to resuscitate without a valid order)
• Against CPR: Autonomy (patient's previously expressed wish for DNACPR), Non-maleficence (futile CPR causes suffering), Quality of life consideration with advanced dementia
• Action: In the absence of a documented DNR order, commence CPR (legal default) while contacting the clinical team to verify patient's advance directive. In the acute situation, the documented status takes precedence over verbal reports.

Stem: "Alzheimer's disease is the most common underlying cause of dementia. What is the MOST COMMON gene contributing to the risk of developing Alzheimer's disease? A. APOE gene B. COMT gene C. SERT gene D. TRIO gene"

Answer: A. APOE gene

Rationale: ApoE ε4 is the most well-established genetic risk factor for late-onset AD. PS1, PS2, and APP are autosomal dominant mutations causing early-onset familial AD but are rare. COMT relates to catecholamine metabolism (schizophrenia), SERT to serotonin transport (depression).