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alzheimer's disease and dementia

progressive neurodegenerative disorder and the most common cause of dementia, characterised by amyloid plaques and neurofibrillary tangles causing progressive memory loss and cognitive decline

neurologycommonchronic

About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

The Bottom Line

  • Alzheimer's disease is the most common cause of dementia (~60–70%), followed by vascular dementia, Lewy body dementia, and frontotemporal dementia
  • Insidious onset of progressive memory loss (especially episodic/short-term memory) with preserved procedural memory early on
  • Diagnosis: clinical assessment + cognitive testing (ACE-III or MMSE) + MRI brain (medial temporal lobe atrophy)
  • First-line treatment (mild-moderate): acetylcholinesterase inhibitor — donepezil 5–10 mg OD (or rivastigmine, galantamine)
  • Moderate-severe: add or switch to memantine (NMDA receptor antagonist)

Overview

Dementia is a clinical syndrome of progressive cognitive decline sufficient to interfere with daily functioning. Alzheimer's disease (AD) is the most common cause, accounting for approximately 60–70% of cases. It is characterised pathologically by extracellular amyloid-beta plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau protein), leading to neuronal loss, brain atrophy (particularly hippocampi and temporal lobes), and cholinergic neurotransmitter deficiency. Mixed dementia (AD + vascular) is very common, especially in older patients.

Epidemiology

Approximately 900,000 people in the UK live with dementia, projected to exceed 1 million by 2030. Prevalence doubles approximately every 5 years after age 65. Risk factors for AD include advancing age (strongest risk factor), female sex, Down syndrome, family history, ApoE4 allele (strongest genetic risk factor for late-onset AD), cardiovascular risk factors (hypertension, diabetes, obesity, smoking), low educational attainment, social isolation, and hearing loss. Early-onset dementia (<65 years) accounts for ~5% of cases.

Clinical Features

Symptoms
Progressive short-term (episodic) memory loss — asking repetitive questions, losing items, forgetting recent events
Difficulty with word-finding (anomia) and language (progressive aphasia)
Visuospatial dysfunction — getting lost in familiar places, difficulty judging distances
Impaired executive function — poor planning, decision-making, problem-solving
Changes in personality and behaviour — apathy, social withdrawal, disinhibition
Difficulty with activities of daily living (dressing, cooking, finances)
Behavioural and psychological symptoms: agitation, aggression, delusions, wandering, sleep disturbance
Signs
Impaired performance on cognitive testing: ACE-III <88/100 or MMSE <24/30 suggests dementia
Often well-presented and socially appropriate early in disease ("facade" effect)
Disorientation to time and place
Neurological examination often normal early — no focal signs (unlike vascular dementia)
Late stages: myoclonus, seizures, primitive reflexes, dysphagia

Investigations

First-line
Cognitive assessmentAddenbrooke's Cognitive Examination (ACE-III) or MMSE. Also 6-CIT or GPCOG in primary care for initial screening
BloodsTo exclude reversible causes of cognitive impairment: FBC, U&Es, LFTs, calcium, glucose, TFTs, B12, folate, HIV (if risk factors). Not all cognitive decline is dementia
MRI brainStructural imaging recommended for all (NICE NG97). AD: medial temporal lobe and hippocampal atrophy. Also excludes structural causes (tumour, subdural, NPH)
Second-line
FDG-PET or SPECT (perfusion)If diagnosis uncertain — shows temporo-parietal hypometabolism/hypoperfusion in AD
CSF biomarkersLow amyloid-beta 42, raised total tau and phospho-tau support AD diagnosis — used in specialist centres
Specialist
Amyloid PETDemonstrates amyloid deposition in vivo — mainly research tool, but used in diagnostic uncertainty
Neuropsychological assessmentDetailed cognitive profiling — especially useful in young-onset or atypical presentations
1
Pharmacological
  • Mild-moderate AD: acetylcholinesterase inhibitor (AChEI) — donepezil 5 mg OD (increase to 10 mg after 4–6 weeks), or rivastigmine, or galantamine
  • Moderate-severe AD: memantine 5 mg OD titrated to 20 mg OD (NMDA receptor antagonist). Can be used alone or with AChEI
  • AChEIs should NOT be used in frontotemporal dementia
  • Review response at 3–6 months — continue if clinically beneficial
2
Non-pharmacological
  • Cognitive stimulation therapy (group-based) — recommended for mild-moderate dementia
  • Physical exercise — evidence for slowing cognitive decline
  • Music therapy, art therapy, reminiscence therapy
  • Environmental modifications: good lighting, clear signage, reduce fall hazards
3
Managing behavioural and psychological symptoms (BPSD)
  • Non-pharmacological approaches FIRST: identify triggers, person-centred care, reassurance, distraction
  • Antipsychotics (risperidone) only for severe distress or risk of harm — use lowest dose for shortest time. Increased mortality and stroke risk in dementia
  • Avoid benzodiazepines where possible (increased falls, paradoxical agitation)
4
Support and planning
  • Advance care planning, lasting power of attorney — discuss while capacity retained
  • Carer assessment and support — refer to local Alzheimer's Society and carer services
  • DVLA notification — formal driving assessment may be needed. Group 2 licence revoked at diagnosis
  • Regular comprehensive review including medication review, carer wellbeing, safety, and social care needs

Complications

  • Aspiration pneumonia: Leading cause of death — dysphagia develops in advanced stages
  • Falls and fractures: Visuospatial impairment, gait disturbance, polypharmacy
  • Delirium: People with dementia are highly susceptible — any acute illness can precipitate delirium
  • Carer burden: Depression, anxiety, social isolation in carers — must be assessed and supported
  • Wandering and risk: Getting lost, accidents, vulnerability to harm
  • Weight loss and malnutrition: Forgetting to eat, dysphagia in later stages
UKMLA Exam Tips
  • 1Alzheimer's: insidious onset, progressive short-term memory loss, temporal lobe atrophy on MRI. Vascular: stepwise decline, vascular risk factors, multi-infarct pattern on MRI
  • 2Donepezil (AChEI) = first-line for mild-moderate AD. Memantine for moderate-severe (or intolerant of AChEIs)
  • 3ALWAYS exclude reversible causes: hypothyroidism, B12 deficiency, depression, normal pressure hydrocephalus, subdural haematoma
  • 4Delirium vs dementia: delirium = acute onset, fluctuating, inattention. Dementia = chronic, progressive, stable attention (until late). They frequently coexist
  • 5Do NOT use antipsychotics routinely for BPSD — increased stroke risk and mortality in dementia patients
  • 6ApoE4 allele is the strongest genetic risk factor for late-onset AD (not diagnostic)
  • 7Down syndrome: almost all develop AD pathology by age 40 — amyloid precursor protein gene on chromosome 21
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Verified Sources & References

NICE NG97 — Dementia: assessment, management and support
NICE TA217 — Donepezil, galantamine, rivastigmine and memantine for Alzheimer's disease