AKT · Neurology/Movement & neurodegeneration

Alzheimer's disease

Amyloid plaques + neurofibrillary (tau) tangles → cortical neurodegeneration

Overview

The commonest dementia: insidious, progressive impairment of recent memory first, then language, visuospatial and executive function. Amyloid-β plaques and tau neurofibrillary tangles with cholinergic deficit underlie it. Managed with cholinesterase inhibitors.

Recognise

Insidious onset, gradual progression; EARLY loss of recent (episodic) memory
Later: word-finding/language, getting lost, apraxia, impaired judgement; preserved early insight then lost
Medial temporal/hippocampal atrophy on MRI

Red flags

Rapid decline, focal signs, early gait/falls, fluctuation or early hallucinations → reconsider the dementia subtype or a reversible cause

Differentials & how to tell them apart

Vascular dementiastepwise decline, vascular risk factors, focal signs, white-matter/infarcts on imaging

Lewy body dementiafluctuating cognition, visual hallucinations, parkinsonism, REM sleep behaviour

Frontotemporal dementiayounger, early personality/behaviour or language change, memory relatively spared early

Depression (pseudodementia)low mood, "don’t know" answers, improves with mood treatment

Normal pressure hydrocephalusgait apraxia + incontinence + dementia, reversible with shunt

Investigations

Cognitive testing (MMSE/MoCA/ACE-III); bloods to exclude reversible causes (TFTs, B12/folate, calcium, glucose); MRI/CT (hippocampal atrophy, exclude structural). Diagnose after excluding delirium/depression.

Management

Acetylcholinesterase inhibitor (donepezil) for mild–moderate; memantine for moderate–severe

1Exclude reversible causes/delirium/depression. Cholinesterase inhibitor (donepezil/rivastigmine/galantamine) for mild–moderate AD + cognitive/structured support.Gate: Avoid antipsychotics for behavioural symptoms unless severe risk — they raise stroke and mortality in dementia (especially Lewy body)
2Memantine for moderate–severe or if cholinesterase inhibitors are unsuitable; advance care planning, carer support, driving (DVLA).

Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) — mild–moderate AD (caution: bradycardia)

Memantine (NMDA antagonist) — moderate–severe, or add-on

Key points

Early episodic-memory loss + hippocampal atrophy = Alzheimer. Always exclude reversible mimics (B12, thyroid, depression, NPH) before diagnosing. Antipsychotics are hazardous in dementia.

Monitor & prognosis

Cognition, function, behaviour, carer strain; medication tolerance.

Progressive over ~8–10 years; drugs slow symptoms, not the disease.

Source: NICE NG97 (dementia)