Key Facts

Dementia is a major and growing public health challenge. Early diagnosis allows access to treatment, support, and future planning. Reversible causes must be excluded. A systematic approach to differential diagnosis guides appropriate management.

Epidemiology

~900,000 people in UK with dementia. Prevalence doubles every 5 years after age 65: ~2% at 65-69, ~20% at 85-89. Annual cost to UK economy >£26 billion. Third leading cause of death in UK.

Aetiology

• Alzheimer disease: ~60-70% (amyloid plaques + neurofibrillary tangles)
• Vascular dementia: ~20% (post-stroke or small vessel disease)
• Dementia with Lewy bodies: ~10-15%
• Frontotemporal dementia: ~5% (younger onset)
• Mixed dementia: very common (especially AD + vascular)
• Other: Parkinson disease dementia, Huntington disease, CJD, alcohol-related, NPH

Pathophysiology

Varies by type. Common to all: progressive neuronal loss and synaptic dysfunction → cognitive decline → loss of functional independence. AD: extracellular amyloid-β plaques + intraneuronal neurofibrillary tangles (hyperphosphorylated tau) → neuronal death, cholinergic deficit (basis for cholinesterase inhibitors). Vascular: cerebrovascular disease (infarcts, white matter disease) → neuronal damage. DLB: α-synuclein Lewy bodies in cortex. FTD: tau or TDP-43 protein aggregates in frontal/temporal lobes.

General Features

• Memory loss: typically short-term initially (AD pattern); may be preserved in early FTD
• Language: word-finding difficulty, progressive aphasia
• Executive function: planning, problem-solving, multitasking decline
• Visuospatial: getting lost, difficulty with spatial tasks
• Behavioural/psychiatric: apathy, depression, agitation, psychosis, disinhibition
• Functional decline: loss of independence in ADLs

Pattern Recognition

• AD: insidious onset, progressive episodic memory loss, temporal-parietal atrophy
• Vascular: stepwise deterioration, vascular risk factors, executive/processing speed, focal signs
• DLB: fluctuating cognition, visual hallucinations, parkinsonism, REM sleep disorder
• FTD: personality/behavioural change OR progressive aphasia; younger onset; frontal/temporal atrophy

Red Flags

• Rapid progression (weeks-months) → CJD, autoimmune encephalitis, malignancy
• Young onset (<65) → genetic causes, FTD, metabolic
• Gait disturbance + urinary incontinence + dementia → NPH (potentially reversible)
• Fluctuating consciousness + hallucinations → DLB (avoid antipsychotics)

Cognitive Assessment (NICE NG97)

• Standardised tools: ACE-III (≤88/100 suggestive), MoCA (≤25/30), MMSE (≤24/30), 6-CIT
• Formal neuropsychological assessment: for complex/young-onset cases

Bloods (Exclude Reversible Causes)

• FBC: anaemia, macrocytosis
• U&Es, calcium: metabolic causes
• TFTs: hypothyroidism
• B12 and folate: deficiency
• LFTs and GGT: alcohol-related
• Glucose/HbA1c: diabetes
• Syphilis serology: if risk factors
• HIV: if risk factors

Imaging

• MRI brain (preferred) or CT head: structural atrophy pattern, vascular disease, NPH, space-occupying lesion
  • AD: medial temporal lobe/hippocampal atrophy
  • Vascular: white matter hyperintensities, infarcts
  • FTD: frontal and/or temporal lobe atrophy
  • DLB: relatively preserved medial temporal lobes

Specialist Investigations

• DaTSCAN: reduced uptake in DLB and PDD (normal in AD)
• FDG-PET: patterns of hypometabolism (AD: temporal-parietal; FTD: frontal)
• CSF biomarkers: amyloid-β42 (low in AD), tau/phospho-tau (high in AD); increasingly available
• Amyloid PET: research/specialist use
• EEG: CJD (periodic sharp wave complexes), encephalitis
• Genetic testing: young-onset AD (APP, PSEN1, PSEN2), FTD (MAPT, GRN, C9orf72)

Pharmacological (NICE TA217)

Alzheimer Disease:

• Mild-moderate AD: cholinesterase inhibitors — donepezil 5-10mg OD (commonest), rivastigmine 1.5-6mg BD or patches 4.6-13.3mg/24h, galantamine 8-24mg OD (MR)
• Moderate-severe AD: memantine 10-20mg OD (NMDA receptor antagonist); can be used alone or combined with ChEI
• Side effects of ChEIs: nausea, diarrhoea, insomnia, bradycardia; monitor ECG if cardiac history

Vascular Dementia:

• No specific anti-dementia drugs (ChEIs not routinely recommended for pure vascular dementia)
• Treat vascular risk factors: hypertension, diabetes, hyperlipidaemia, smoking cessation, antiplatelet therapy

DLB:

• ChEIs (especially rivastigmine) — effective for cognitive and neuropsychiatric symptoms
• AVOID antipsychotics (severe neuroleptic sensitivity — potentially fatal)
• If antipsychotic essential: quetiapine (lowest dose, shortest duration)

FTD:

• No effective pharmacological treatment for cognitive decline
• SSRIs for behavioural symptoms (disinhibition, compulsions)
• ChEIs NOT effective (may worsen behaviour)

Non-Pharmacological

• Cognitive stimulation therapy (CST): group activities improving cognition — NICE recommended
• Reminiscence therapy, music therapy, exercise
• Carer support: Alzheimer's Society, respite care, carer assessment
• Advance care planning: lasting power of attorney, ADRT, preferred place of care
• Environmental adaptations: simplify home, safety measures, assistive technology

Behavioural and Psychological Symptoms of Dementia (BPSD)

• Non-pharmacological first: identify triggers, person-centred care, environment
• Antipsychotics: ONLY if severe risk to self/others; short course; review regularly
• Risperidone is the only antipsychotic licensed for short-term use in AD-related aggression

Referral Criteria

• Memory assessment service: all suspected dementia (NICE NG97)
• Young-onset (<65): specialist memory/neurology service
• Rapidly progressive: neurology (exclude CJD, autoimmune)
• Complex behavioural management: old age psychiatry

AD: mean survival ~8-10 years from diagnosis; progressive and invariably fatal. Vascular dementia: variable; stepwise with periods of stability; depends on vascular events. DLB: mean survival ~6-8 years (slightly shorter than AD). FTD: mean survival ~6-8 years from onset. Pneumonia and other infections are the commonest cause of death. Quality of life can be significantly improved with appropriate support and treatment.

Dementia Subtypes Comparison

Reversible Causes of Cognitive Decline