Dementia

Meet the patient

A 78-year-old former maths teacher is brought by her daughter, who is now managing her mother's bills. For two years her mother has asked the same question within minutes, mislaid her keys in the fridge, and last week could not find her way home from the corner shop. She is alert, her speech is fluent, and she laughs at her own forgetfulness — but her daughter quietly says she has stopped cooking and is eating badly. Bloods last month were normal.^[2]

Two exam questions are now live. Is this dementia, or a mimic? — and which subtype is it, because the drug and the prognosis both depend on the answer? The insidious episodic memory loss, preserved social graces, anosognosia, and the threshold crossing into impaired activities of daily living are the fingerprint of Alzheimer disease. The skill is to confirm it is dementia and not a mimic, then to classify the subtype.^[1]

What dementia is — a syndrome, not a disease

Dementia is best defined as an acquired, persistent and usually progressive global impairment of higher cortical function — memory, language, visuospatial skill, executive function, praxis, gnosis and personality — occurring in clear consciousness and severe enough to disrupt activities of daily living (ADLs).^[2]

Three elements of the definition carry weight in a viva:^[1]

• Acquired — distinguishes dementia from intellectual disability (developmental).
• In clear consciousness — distinguishes it from delirium, in which consciousness is clouded and the course is acute and fluctuating.
• Interferes with ADLs — distinguishes it from mild cognitive impairment (MCI), in which decline is present but independence is preserved.^[1]

The DSM-5 (2013) replaced the word "dementia" with major neurocognitive disorder (major NCD) and reserved mild neurocognitive disorder (mild NCD) for the equivalent of MCI. "Dementia" remains the clinical term in everyday practice and in NICE and most national guidelines.^[1]

The clinical skill in dementia is not recognising that a patient is cognitively impaired — it is confirming the diagnosis is truly dementia and not a mimic, identifying the underlying aetiology (because management, prognosis and genetic counselling differ by subtype), and delivering a structured, multidomain plan.^[1]

Classification — aetiology, anatomy, tempo

Dementia is classified along several axes; all four are examinable.^[1]

By aetiology (the classification that matters clinically):^[1]

^[2]

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By tempo of decline: progressive or insidious (Alzheimer, FTD); stepwise (vascular, multi-infarct); fluctuating (dementia with Lewy bodies).^[1]

The 1-year rule distinguishes dementia with Lewy bodies (DLB) from Parkinson disease dementia (PDD): cognitive symptoms arising at least one year before the motor features of parkinsonism equal DLB; cognitive decline arising after established Parkinson disease equals PDD. The pathology is essentially the same (alpha-synuclein); the distinction is clinical and matters for trial recruitment and drug selection.^[4]

How common, how preventable — the Lancet Commission

Dementia is the leading cause of disability in older adults worldwide. The WHO estimates about 55 million people live with dementia globally, with nearly 10 million new cases each year; numbers are projected to triple by 2050, driven by ageing populations, with the steepest rises in low- and middle-income countries including India.^[3]

Prevalence doubles roughly every five years after age 65 — about 1 percent at 60 to 64, rising to over 30 percent after 90. Increasing age is the single strongest non-modifiable risk factor.^[2]

The 2020 Lancet Commission^[3] identified 12 modifiable factors responsible for about 40 percent of worldwide dementia that is theoretically preventable, grouped by life-stage:

• Early life — low educational attainment.
• Mid life — hearing loss, traumatic brain injury (TBI), hypertension, obesity, excessive alcohol.
• Later life — smoking, depression, social isolation, physical inactivity, diabetes, air pollution.^[1]

Genetics of Alzheimer disease (high-yield):^[1]

• APOE epsilon-4 — the strongest genetic risk factor for sporadic, late-onset AD; one copy increases risk 2 to 3 times, two copies 8 to 12 times. APOE epsilon-2 is protective. APOE is a risk modifier, not deterministic.
• Autosomal-dominant (familial) early-onset AD — mutations in PSEN1 (chromosome 14), PSEN2 (chromosome 1) and APP (chromosome 21). Rare (under 1 percent of AD), onset typically 30 to 60 years, 50 percent chance of transmission to each child. APP on chromosome 21 explains the near-universal development of Alzheimer pathology in Down syndrome by the fourth to fifth decade.^[1]

Pathophysiology — the protein that misfolds defines the disease

Dementia is a proteinopathy-driven neuronal loss; the protein that misfolds defines the disease.^[2]

Alzheimer disease — the amyloid cascade hypothesis. Amyloid precursor protein (APP), encoded on chromosome 21, is cleaved by beta- and gamma-secretases to produce amyloid-beta 42 (Abeta-42), an aggregation-prone peptide. Over-production or impaired clearance leads to extracellular deposition as senile (neuritic) plaques, especially in the neocortex and hippocampus. Abeta-42 oligomers are synaptotoxic, triggering hyperphosphorylation of tau. Normal tau stabilises axonal microtubules; hyperphosphorylated tau detaches and aggregates intraneuronally as paired helical filaments that form neurofibrillary tangles (NFTs). Tangles spread along a stereotyped path (Braak staging) — from the transentorhinal region, to the hippocampus, to the neocortex.^[2]

The earliest and most severe neurotransmitter deficit is cholinergic — degeneration of the nucleus basalis of Meynert (the basal forebrain cholinergic projection). This is the rationale for cholinesterase inhibitors.^[1]

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Vascular dementia. Cognitive loss from cerebrovascular disease operates through several mechanisms: multi-infarct (cumulative damage from large cortical strokes); single strategic infarct (thalamus, angular gyrus, basal forebrain, caudate); small-vessel disease (lipohyalinosis of deep penetrating arteries producing lacunes and white-matter hyperintensities — leukoaraiosis, damaging fronto-subcortical circuits); and Binswanger (subcortical arteriosclerotic encephalopathy — severe white-matter change with hypertension).^[2]

Dementia with Lewy bodies. Misfolding and intracellular accumulation of alpha-synuclein as Lewy bodies in cortical and subcortical (brainstem) neurons. The degeneration is both dopaminergic (substantia nigra → parkinsonism) and cholinergic (basal forebrain and pedunculopontine nucleus → cognitive and visual-hallucination features), which explains why DLB responds to cholinesterase inhibitors and why visual hallucinations are prominent and detailed.^[4]

Frontotemporal dementia. Frontal and anterior temporal lobe degeneration with frontotemporal lobar degeneration (FTLD) pathology. The substrate is most commonly TDP-43 (about half), then tau (mutations in the MAPT gene on chromosome 17; Pick bodies with tau-3R), and rarely FUS. The C9orf72 hexanucleotide repeat expansion (chromosome 9) causes familial FTD-ALS overlap.^[2]

Prion disease — sporadic Creutzfeldt-Jakob disease (sCJD). Misfolding of the prion protein (PrP) into the infectious PrP-scrapie (PrP-Sc) conformation, which templates conversion of normal PrP and accumulates as spongiform change with rapid (weeks-to-months) neuronal loss. The causative gene PRNP is on chromosome 20.^[1]

The clinical signatures — each subtype has a fingerprint

The shared core is progressive cognitive decline that crosses the threshold into functional impairment. Beyond that, each subtype has a recognisable signature.^[2]

Alzheimer disease — the prototypical cortical dementia. The earliest and most prominent deficit is recent (episodic) memory — forgetting recent conversations, repeating questions, misplacing items — with remote memory and social graces preserved early on. The patient typically lacks insight (anosognosia). Language follows — anomia (word-finding) progressing to fluent aphasia — then visuospatial dysfunction (getting lost in familiar places) and executive dysfunction. Motor and sensory examination is typically normal until late.^[2]

Vascular dementia — classically stepwise deterioration, each step corresponding to a new infarct, with intervening plateaus. The cognitive profile is fronto-subcortical: executive dysfunction (planning, set-shifting), slowing (bradyphrenia), processing-speed deficit, with memory relatively less affected than in AD. Clinical signs of the strokes are often present: gait disturbance, focal weakness, pseudobulbar signs (dysarthria, emotional lability, hyperreflexia, extensor plantars), urinary urgency or incontinence. Vascular risk factors (hypertension, diabetes, AF) are typically present.^[1]

Dementia with Lewy bodies — the four core clinical features:^[4]

1. Fluctuating cognition — marked variation in attention and alertness on a day-to-day or hour-to-hour basis.
2. Recurrent, well-formed, detailed visual hallucinations — often of people or animals, typically not frightening early on.
3. Spontaneous parkinsonism features (rigidity, bradykinesia — tremor less prominent than in idiopathic PD).
4. Rapid eye movement (REM) sleep behaviour disorder (RBD) — loss of normal REM atonia, so the patient acts out dreams (shouting, thrashing) — often preceding the dementia by years.^[4]

Supportive features: severe neuroleptic sensitivity, autonomic dysfunction (orthostatic hypotension, constipation, urinary incontinence), hypersomnia, depression, anosmia. Memory may be relatively better preserved than in AD early on, but visuospatial and attentional deficits are prominent — DLB patients do disproportionately badly on clock-drawing and trail-making.^[4]

Frontotemporal dementia — onset typically younger (45 to 65 years). Two broad syndromes:^[1]

• Behavioural variant (bvFTD) — the commonest. Progressive personality change: disinhibition (socially inappropriate remarks, impulsivity), apathy or loss of empathy, repetitive or compulsive behaviours, dietary change (sweet tooth, hyperphagia), executive dysfunction with relative memory and visuospatial sparing. Insight lost early.
• Primary progressive aphasia (PPA) — three subtypes: semantic (fluent but empty speech, loss of word meaning, anterior temporal atrophy, often TDP-43 type C), non-fluent or agrammatic (effortful halting speech, apraxia of speech, inferior frontal-insular atrophy, tau), and logopenic (slow, word-finding pauses, impaired repetition, posterior temporal or parietal atrophy — often an atypical AD variant).^[2]

Normal-pressure hydrocephalus — the classic triad of gait apraxia (magnetic, shuffling, broad-based, "feet glued to the floor"), urinary incontinence, and cognitive slowing (subcortical). Potentially reversible.^[1]

The mimics you must exclude before you commit to the label

The diagnosis of dementia is always a diagnosis of exclusion of mimics.^[2]

^[2]

Distinguishing depression (pseudodementia) from true dementia — a recurring exam favourite:^[1]

^{[1] [1]}

The bedside cognitive exam — three layers

A structured cognitive assessment has three layers: cognitive testing, functional assessment, and behavioural or psychiatric assessment, all anchored to a collateral history from a reliable informant (the family knows first).^[1]

Cognitive screening instruments:^[1]

• Mini-Mental State Examination (MMSE, Folstein) — a 30-point bedside test sampling orientation (10), registration (3), attention or calculation (5 — serial 7s or spelling WORLD backwards), recall (3), language (8 — naming, repetition, 3-stage command, reading, writing) and visuoconstruction (1 — intersecting pentagons). A score under 24 out of 30 suggests impairment (adjusted for age and education). Limitations: insensitive to mild or early disease and to executive dysfunction, biased by education and language.
• Montreal Cognitive Assessment (MoCA) — also 30-point; cut-off under 26 out of 30 is abnormal; more sensitive than the MMSE for early or mild disease and executive dysfunction, and the preferred screen for MCI and FTD.
• Clock-drawing test — ask the patient to draw a clock face with all the numbers and set the hands to "11:10". A normal clock excludes most significant dementia; errors suggest right parietal or visuospatial dysfunction — disproportionately affected in DLB and in posterior cortical atrophy (a visual variant of AD).
• Addenbrooke's Cognitive Examination III (ACE-III) — a 100-point battery; useful in specialist clinics to profile the subtype. Frontal Assessment Battery (FAB) for suspected FTD.^[1]

Functional scales: ADLs (Basic — Barthel) and IADLs (Lawton Instrumental: shopping, cooking, housekeeping, laundry, transport, phone use, medications, finances). Functional impairment is the threshold between MCI and dementia.^[1]

Bedside neurological examination in suspected dementia: look for focal signs (stroke, tumour), parkinsonism (DLB, PDD, PSP), gait apraxia and wide-based ataxic gait (NPH), primitive reflexes (frontal release — grasp, palmomental, snout) in FTD or advanced AD, myoclonus (CJD, severe AD), paratonia (gegenhalten). Always examine hearing and vision — sensory loss masquerades as dementia.^[1]

Investigations — exclude the reversible, identify the aetiology

The goal of investigation is twofold: to exclude reversible causes and to identify the underlying aetiology.^[1]

First-line blood tests (every patient):^[1]

• Full blood count, ESR; urea and electrolytes, calcium, glucose, HbA1c, LFTs.
• Thyroid function (TSH) — hypothyroidism is a classic reversible mimic.
• Vitamin B12 and folate — deficiency is reversible.
• Syphilis serology (treponemal and non-treponemal) — neurosyphilis is treatable.
• HIV serology (where risk or in young-onset); where relevant, drug levels, alcohol markers, copper or ceruloplasmin (young), thiamine.^[1]

Structural neuroimaging — MRI brain (preferred) or CT if MRI contraindicated: to exclude surgical or treatable lesions (tumour, subdural haematoma, abscess), and to identify patterns supportive of a subtype — medial temporal or hippocampal atrophy (AD, rated on the MTA score — Scheltens scale, 0 to 4 per side); white-matter hyperintensities, lacunes, strategic infarcts (vascular); frontal or anterior temporal atrophy (FTD); disproportionate ventricular enlargement over sulcal atrophy (NPH); cortical ribboning or basal-ganglia hyperintensity on diffusion-weighted imaging (CJD).^[1]

Functional and molecular neuroimaging: FDG-PET or SPECT (temporoparietal hypometabolism in AD; occipital hypometabolism with caudate involvement in DLB; frontal or temporal in FTD); amyloid PET; DAT-SPECT — reduced striatal uptake supports DLB over AD.^[4]

CSF biomarkers (when the diagnosis is uncertain or a disease-modifying drug is being considered): low amyloid-beta 42 (and low Abeta-42 or 40 ratio) reflects brain amyloid deposition; high total tau and high phospho-tau-181 reflects neuronal injury and tau pathology. The Abeta-42 down, tau up pattern has high sensitivity and specificity for AD pathology even at the MCI stage. 14-3-3 protein and RT-QuIC in CSF support prion disease (sCJD).^[1]

EEG: typically normal or shows non-specific slowing in AD; periodic sharp-wave complexes at 1 to 2 Hz are characteristic of sporadic CJD; slowing with fluctuation in DLB.^[1]

Management — safety first, then the drug ladder

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There is no acute resuscitation bundle for chronic dementia as there is for stroke or sepsis — but every dementia encounter must address the safety domains that drive harm and admission.^[1]

Safety assessment at every visit:^[1]

• Driving — in many jurisdictions (including the UK DVLA) a diagnosis of dementia triggers a legal duty to notify the licensing authority; fitness is judged on functional ability and insight, not diagnosis alone.
• Cooking, smoking, heating — fire risk with forgotten pans or unattended cigarettes.
• Medication — ability to self-administer safely; consider a dosette box or blister pack.
• Wandering and getting lost — identification bracelet, GPS tracker, door alarms.
• Falls — home hazard assessment, night-lights, mobility aids.
• Financial safeguarding — power of attorney, scam and abuse risk.^[1]

Capacity and best-interest decisions: assess mental capacity for each specific decision using the test in the relevant capacity legislation (in England and Wales, the Mental Capacity Act 2005 — a two-stage functional and diagnostic test). When capacity is lacking, decisions are made in the patient's best interests, consulting family or attorneys; consider advance decisions (living wills) and Lasting Power of Attorney while capacity remains.^[1]

Cholinesterase inhibitors — first-line for mild-to-moderate AD and DLB

^{[11] [1]}

Mechanism: inhibit acetylcholinesterase → increase synaptic acetylcholine, partially compensating for the cholinergic deficit. Effect size is modest — mean MMSE improvement of about 1 to 2 points, with stabilisation for 6 to 12 months rather than reversal. Review benefit at 3 months; continue if cognition, behaviour or function is stable or improved; stop if deterioration continues at the pre-treatment rate.^[1]

Memantine — for moderate-to-severe AD

For moderate-to-severe AD (MMSE under about 20) and as add-on in moderate disease.^[1][6]

• Dose: the licensed maintenance dose is 20 mg per day (or 28 mg extended release once daily); trials pooled by Cochrane analysed this licensed dose at six to seven months.
• Mechanism: a moderate-affinity, uncompetitive NMDA-receptor antagonist of glutamate signalling.
• Benefit: small but consistent in moderate-to-severe AD — better global rating, about 3 SIB points on cognition, about 1 ADL-19 point on function, about 2 NPI points on behaviour; no benefit shown in mild AD (MMSE 20 to 23).
• Side-effects: dizziness is more frequent than with placebo (about 6 versus 4 percent), headache possibly slightly so; discontinuation rates overall similar to placebo.
• Combination ChEI plus memantine in moderate-to-severe AD: added to stable donepezil, memantine outperformed placebo-add-on on cognition, function and global status at 24 weeks, with fewer patients showing marked clinical worsening.^[7][6]

Anti-amyloid antibodies — for early, biomarker-confirmed AD

For MCI or mild dementia due to AD, amyloid-positive.^[5] Lecanemab — anti-amyloid-beta protofibril IgG1. Clarity AD (van Dyck 2023, NEJM) showed a 27 percent slowing of cognitive decline on the CDR-SB over 18 months (a difference of about 0.45 points) versus placebo, with significant amyloid clearance on PET. Dose: 10 mg per kg intravenously every two weeks. Monitor with serial MRI for amyloid-related imaging abnormalities (ARIA-E oedema and ARIA-H microhaemorrhage); most ARIA is asymptomatic but serious events occur, and anticoagulation increases haemorrhage risk. APOE epsilon-4 carriers, especially homozygotes, are at higher ARIA risk — the Appropriate Use Recommendations advise genotyping to inform the risk discussion before treatment.^[5][10]

Donanemab — anti-pyroglutamate amyloid IgG1; similar efficacy and ARIA profile, with target-to-clear stopping rules.^[1]

BPSD — behavioural and psychological symptoms of dementia

BPSD affects most patients at some stage, drives carer strain and institutionalisation, and is the commonest reason for emergency dementia presentations.^[1]

Stepwise approach:^[8]

1. Identify and treat precipitants — pain, constipation, urinary infection, hunger, thirst, sensory deprivation, medication side-effect, environmental change. Pain is the single most under-treated driver.
2. Non-pharmacological first — person-centred care, structured routine, validation therapy, music, aromatherapy, sensory stimulation, avoid confrontation, modify the environment. The expert panel ranks these first-line: evidence of efficacy with limited adverse effects, though uptake in practice remains poor.^[8]
3. Pharmacotherapy only if distress or risk is severe — an SSRI such as citalopram for agitation in AD has some trial evidence; otherwise a short course of atypical antipsychotic at the lowest effective dose for the shortest time, with documented regular review and a frank risk discussion (stroke, mortality). Avoid typicals; no drug is approved for this indication.^[8]
4. Depression in dementia — SSRI (sertraline, citalopram); tricyclics worsened by anticholinergic load (avoid).
5. Sleep disturbance — sleep hygiene, bright-light therapy; avoid benzodiazepines (deliriogenic); melatonin may help RBD.^[1]

Non-pharmacological core — the foundation, not an add-on

• Cognitive stimulation therapy (CST) — group sessions, evidence-based benefit in mild-moderate AD.
• Regular physical exercise — improves cognition, mood, function.
• Social engagement — combats isolation.
• Hearing aids (in the hearing-impaired — the largest single mid-life modifiable risk factor).
• Diet — Mediterranean or MIND pattern associated with lower incidence.
• Multidomain interventions (FINGER model) — combined vascular, cognitive, exercise and dietary intervention.^[3][1]

Carer-focused plan. Carer strain predicts institutionalisation. Offer psychoeducation, respite care, support groups, behavioural-management training, and screen carers for depression. Plan early for advance decisions, Lasting or Enduring Power of Attorney, finances, and future care preferences while capacity remains.^[1]

How dementia patients come to harm (the preventable list)

• Missing delirium in a demented elderly patient — assume a new acute change has a precipitant until proven otherwise^[1]
• Giving a typical antipsychotic in DLB — fatal neuroleptic sensitivity^[4]
• Labelling depression as dementia (pseudodementia) — undertreats a treatable illness^[1]
• Missing NPH in a "dementia plus falls plus incontinence" patient^[1]
• Over-diagnosing dementia from a low MMSE without considering education, language, sensory loss, anxiety or delirium^[1]
• Under-investigating young-onset dementia — the differential is broader (genetic, prion, autoimmune, Wilson, leucodystrophy) and reversible or heritable causes are over-represented^[1]
• Anticholinergic burden — oxybutynin, tricyclics, antihistamines worsen cognition; review and deprescribe^[1]
• Benzodiazepines — deliriogenic; avoid^[1]
• Missing caregiver burnout and elder abuse — recognise carer strain (Zarit Burden Interview) and safeguard when neglect or abuse is suspected^[1]

Special populations

^{[2] [4]}

Prognosis — the trajectory depends on the subtype

Dementia is progressive and incurable in the degenerative subtypes; the trajectory and median survival differ by aetiology.^[2]

• Alzheimer disease — median survival 8 to 10 years from diagnosis (longer from symptom onset); some live 15 to 20 years.
• Vascular dementia — variable, determined by stroke burden and comorbidity; median 3 to 5 years but with wide spread.
• Dementia with Lewy bodies — 5 to 7 years, often faster than AD; high mortality from falls, aspiration and neuroleptic sensitivity.
• Frontotemporal dementia — 6 to 11 years, faster with ALS-overlap.
• Creutzfeldt-Jakob disease — median 4 to 6 months; invariably fatal.^[1]

Predictors of rapid decline: younger onset, lower baseline cognition, parkinsonism or falls, behavioural disturbance, low CSF Abeta-42 with high tau, hippocampal atrophy on MRI, and APOE epsilon-4 homozygosity (AD).^[1]

Institutionalisation is driven less by cognition than by behavioural disturbance (especially aggression), incontinence, wandering, carer strain, and loss of ADLs.^[1]

End-of-life considerations: dementia is now recognised as a terminal illness. Advance care planning should begin early — while capacity allows — covering future care preferences, resuscitation status, hospital versus home management of infections, and artificial nutrition or hydration. As the disease advances, focus shifts to comfort, dignity, symptom control (pain, agitation, secretions, dyspnoea) and family support — often through palliative care or hospice. Aspiration pneumonia and sepsis are the usual terminal events.^[1]

The named evidence — what changed practice

NICE NG97 (2018, UK)^[1] — care by a memory-assessment service; ChEIs (donepezil, rivastigmine, galantamine) for mild-moderate AD (the three agents are clinically equivalent — choice by tolerability or comorbidity); memantine for moderate-severe AD or where ChEIs are not tolerated; ChEIs reviewed at 3 months then 6-monthly; group cognitive stimulation therapy for mild-moderate; structured non-pharmacological measures first for BPSD, with antipsychotics only short-term for severe distress and reviewed every 3 months; offer carers psychoeducation and support. NICE does not currently recommend routine amyloid PET or anti-amyloid antibodies outside trials or specialist commissioning.

NIA-AA Research Framework (2018) recast AD biologically as a biomarker-defined entity using the AT(N) system — A for Amyloid (low CSF Abeta-42 or positive amyloid PET), T for Tau (high CSF phospho-tau or positive tau PET), (N) for Neurodegeneration (high CSF total tau, atrophy on MRI, hypometabolism on FDG-PET). A biomarker-confirmed diagnosis requires A-positive (with T for "AD"), irrespective of clinical stage — this underpins the eligibility criteria for the new anti-amyloid antibodies.^[1]

European intersocietal biomarker recommendations (Frisoni 2024)^[1] codify when to use blood, CSF and PET biomarkers, including the emerging plasma p-tau217 blood test as a triage tool before confirmatory CSF or PET.

2020 Lancet Commission (Livingston)^[3] — the key prevention paper: 12 modifiable risk factors account for about 40 percent of dementia (up from 35 percent in the 2017 report, after adding excessive alcohol, TBI and air pollution).

Clarity AD (van Dyck 2023, NEJM)^[5] — phase 3 trial of lecanemab in early AD: 27 percent relative slowing of decline on CDR-SB (about 0.45 absolute points over 18 months); 17 percent relative reduction in amyloid on PET; ARIA-E in 12.6 percent and ARIA-H in 17.3 percent (symptomatic in about a quarter, with three treatment-related deaths in extension data). The first rigorously positive disease-modifying trial in AD.^[5]

Regional differences: In India, prevalence is rising with longevity; the vascular burden is higher (driven by hypertension and diabetes), so mixed AD-vascular is common. Cultural norms favour family-based home care, with state-funded memory clinics still uneven; the Indian Consortium on Dementia and AIIMS or NIMHANS guidelines adapt international evidence to local resources. Self-medication and polypharmacy drive high anticholinergic burden.^[1]

The mantra, and the red flag

The mantra: exclude the mimics, classify the subtype, avoid the fatal drug error.^[1]

Ward-round test — three stems, thirty seconds each

Stem 1 — the maths teacher from the top of the topic (answer)ShowHide

The 78-year-old with two years of insidious episodic memory loss, repetitive questioning, getting lost near home, stopped cooking, normal bloods, preserved social graces and anosognosia. What is the diagnosis and the first-line drug? Model: Alzheimer disease — the prototypical cortical dementia, with insidious episodic memory loss as the earliest feature, anosognosia, and the threshold crossing into impaired ADLs. Screen with MMSE (under 24) or MoCA (under 26), confirm with MRI (medial temporal or hippocampal atrophy, raised MTA score), and exclude reversible causes (B12, folate, TSH, calcium, syphilis, HIV, NPH — though her bloods are already normal, send the rest).^[1] First-line drug is a cholinesterase inhibitor — donepezil, 5 mg once daily, stepped up to 10 mg if tolerated — for mild-moderate AD; donepezil at 5 and 10 mg daily improved cognition and global rating versus placebo over 24 weeks in the pivotal trial.^[11] Address driving (DVLA notification), medication safety, and carer support.^[2]

Stem 2 — fluctuating confusion with detailed hallucinations (answer)ShowHide

An 80-year-old man has fluctuating cognition, vivid visual hallucinations of children in his bedroom, mild rigidity, and acts out violent dreams at night. What is the syndrome, the supportive biomarker, and the drug you must NEVER give? Model: Dementia with Lewy bodies (DLB) — four core clinical features (fluctuating cognition, recurrent detailed visual hallucinations, spontaneous parkinsonism, REM sleep behaviour disorder). A DAT-SPECT showing reduced striatal uptake is the supportive biomarker (4th DLB Consortium criteria). ChEIs (rivastigmine has the strongest evidence) help both cognition and hallucinations. The drug you must never give is a typical antipsychotic (haloperidol) — DLB carries severe neuroleptic sensitivity (rigidity, hyperthermia, rhabdomyolysis, death, sometimes after a single dose). If an antipsychotic is unavoidable, use low-dose quetiapine.^[4]

Stem 3 — the reversible triad (answer)ShowHide

A 75-year-old woman has a shuffling, broad-based gait ("feet glued to the floor"), new urinary incontinence, and slowing of thought over six months. What is the diagnosis, the imaging sign, and the potentially curative treatment? Model: Normal-pressure hydrocephalus (NPH) — the classic triad of gait apraxia, urinary incontinence, and subcortical dementia. The imaging sign is ventriculomegaly out of proportion to sulcal atrophy on MRI. Diagnosis rests on the clinical picture plus this imaging, and transient CSF removal — a CSF tap test by lumbar puncture or external lumbar drainage — adds diagnostic certainty and helps predict response before committing to a ventriculoperitoneal shunt, which is effective but carries real morbidity. Never label a triad patient as Alzheimer without imaging.^[9]

References11ShowHide

1. [1]Frisoni GB, Festari C, Massa F, et al. European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders Lancet Neurol, 2024.PMID 38365381
2. [2]Schneider JA. Neuropathology of Dementia Disorders Continuum (Minneap Minn), 2022.PMID 35678405
3. [3]Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission Lancet, 2020.PMID 32738937
4. [4]McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium Neurology, 2017.PMID 28592453
5. [5]van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer's Disease N Engl J Med, 2023.PMID 36449413
6. [6]McShane R, Westby MJ, Roberts E, et al. Memantine for dementia Cochrane Database Syst Rev, 2019.PMID 30891742
7. [7]Atri A, Molinuevo JL, Lemming O, et al. Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy Alzheimers Res Ther, 2013.PMID 23336974
8. [8]Kales HC, Gitlin LN, Lyketsos CG, et al. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel J Am Geriatr Soc, 2014.PMID 24635665
9. [9]Tsakanikas D, Relkin N. Normal pressure hydrocephalus Semin Neurol, 2007.PMID 17226742
10. [10]Cummings J, Apostolova L, Rabinovici GD, et al. Lecanemab: Appropriate Use Recommendations J Prev Alzheimers Dis, 2023.PMID 37357276
11. [11]Rogers SL, Farlow MR, Doody RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group Neurology, 1998.PMID 9443470