Key Facts

Dementia is not a normal part of ageing. Early diagnosis enables access to treatment, support, and future planning including advance care planning.

Epidemiology

• ~900,000 people in the UK; ~70,000 people <65 (young-onset dementia)
• Prevalence doubles every 5 years after age 65
• Leading cause of death in England and Wales
• Annual NHS cost: approximately £26 billion

Aetiology

• Alzheimer's disease: amyloid plaques (Aβ42) and neurofibrillary tangles (hyperphosphorylated tau)
• Vascular dementia: cerebrovascular disease (multi-infarct, small vessel disease, strategic infarct)
• Lewy body dementia: α-synuclein Lewy bodies in cortex and brainstem
• Frontotemporal dementia: tau or TDP-43 protein aggregates; frontal/temporal atrophy
• Risk factors: age, family history, APOE ε4 allele (Alzheimer's), hypertension, diabetes, obesity, smoking, depression, low education

Pathophysiology

• Alzheimer's: amyloid cascade hypothesis - Aβ42 aggregation → neuritic plaques → tau hyperphosphorylation → neurofibrillary tangles → synaptic loss → neuronal death; cholinergic deficit (basis for AChEI treatment)
• Vascular: white matter ischaemia, lacunar infarcts, strategic infarcts (thalamus, angular gyrus)
• Lewy body: Lewy body deposition in cortex → cholinergic and dopaminergic disruption
• Frontotemporal: frontal/temporal neuronal loss → personality change, language impairment

Alzheimer's Disease

• Insidious onset, gradual progression
• Early: short-term memory loss (episodic memory), word-finding difficulty
• Moderate: disorientation, impaired ADLs, behavioural changes
• Severe: loss of speech, immobility, incontinence

Vascular Dementia

• Stepwise decline (episodes of deterioration)
• Focal neurological signs
• Emotional lability
• Preservation of personality (early)

Lewy Body Dementia

• Visual hallucinations (detailed, recurrent)
• Fluctuating cognition (marked fluctuations in alertness and attention)
• Parkinsonism (rigidity, bradykinesia, but tremor less prominent)
• REM sleep behaviour disorder (acts out dreams)
• Autonomic dysfunction, falls

Frontotemporal Dementia

• Behavioural variant: personality change, disinhibition, apathy, loss of empathy
• Semantic: loss of word meaning
• Progressive non-fluent aphasia: effortful speech, grammatical errors
• Memory relatively preserved early

Red Flags

• Rapid cognitive decline (weeks-months): consider CJD, autoimmune encephalitis, tumour
• Young onset (<65): genetic causes, metabolic
• Focal neurological signs: stroke, space-occupying lesion
• Gait disturbance + incontinence + dementia: normal pressure hydrocephalus (potentially reversible)

Bedside

• Cognitive assessment: ACE-III (88 or below abnormal), MoCA (≤25 abnormal), MMSE, 6-CIT
• Collateral history from carer/family (essential)
• Functional assessment (ADLs, IADLs)
• Behavioural assessment
• Depression screening (GDS-15)

Bloods

• Dementia screening bloods (to exclude reversible causes): FBC, U&Es, LFTs, calcium, TFTs, B12, folate, HbA1c
• Syphilis serology (if indicated)
• HIV (if risk factors)

Imaging

• MRI brain (preferred): hippocampal atrophy (Alzheimer's), vascular changes (WMH, infarcts), frontotemporal atrophy
• CT head: alternative if MRI contraindicated
• FDG-PET or SPECT: if diagnostic uncertainty (e.g. differentiating Alzheimer's from FTD)
• DaTSCAN (FP-CIT SPECT): abnormal in Lewy body dementia (reduced dopamine transporter uptake)

Special Tests

• CSF: Aβ42 (low) and tau/p-tau (elevated) in Alzheimer's (specialist use)
• Amyloid PET: emerging diagnostic tool
• Genetic testing: familial Alzheimer's (APP, PSEN1, PSEN2), FTD (MAPT, GRN, C9orf72)
• EEG: CJD (periodic sharp wave complexes), non-convulsive status

Non-pharmacological

• Cognitive stimulation therapy (CST): NICE-recommended; group-based; improves cognition and QoL
• Reminiscence therapy: using past experiences to stimulate memory
• Physical exercise: regular aerobic and resistance exercise
• Occupational therapy: strategies for maintaining independence
• Carer support: education, respite care, support groups (Alzheimer's Society)
• Environmental modifications: clear signage, good lighting, memory aids
• Advance care planning: discuss early while capacity present
• Lasting Power of Attorney: encourage early discussion

Pharmacological

• Mild-moderate Alzheimer's disease:
  • Donepezil 5mg OD → increase to 10mg after 4-6 weeks (AChEI)
  • Alternatives: rivastigmine (patches 4.6-13.3mg/24h), galantamine 8-24mg MR OD
• Moderate-severe Alzheimer's:
  • Memantine 5mg OD → titrate to 20mg OD over 4 weeks (NMDA antagonist)
  • Can use in combination with AChEI
• Lewy body dementia: AChEIs (rivastigmine preferred); avoid antipsychotics (neuroleptic sensitivity)
• Vascular dementia: no specific pharmacological treatment; optimise cardiovascular risk factors
• FTD: no disease-modifying treatment; SSRIs for behavioural symptoms (trazodone for agitation)
• BPSD (behavioural and psychological symptoms):
  • First-line: non-pharmacological approaches
  • If severe/distressing: risperidone 250mcg-1mg OD (only antipsychotic licensed for BPSD; short course, regular review)

Surgical/Interventional

• VP shunt for normal pressure hydrocephalus (potentially reversible dementia)

Referral Criteria

• Suspected dementia: memory assessment service/memory clinic
• Young-onset (<65): specialist neurology/neuropsychiatry
• Diagnostic uncertainty: specialist neuroimaging, CSF biomarkers
• Complex BPSD: old age psychiatry
• Carer strain: social services, Alzheimer's Society

• Alzheimer's disease: mean survival 8-10 years from diagnosis; progressive
• Vascular dementia: variable; depends on cardiovascular management; median survival 5 years
• Lewy body dementia: median survival 5-8 years; high risk of falls and aspiration
• Frontotemporal dementia: median survival 6-8 years (behavioural variant); 3-5 years (motor neurone disease variant)
• AChEIs: modest but significant improvement in cognition, function, and behaviour (delay decline by ~6-12 months)
• Dementia is a terminal illness; palliative care approach in advanced stages
• Leading cause of death in England and Wales

Comparison of Dementia Subtypes

Cognitive Assessment Tools