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Neurology

Alzheimer Disease

Most common cause of dementia; progressive amnestic memory loss from amyloid-beta plaques and tau tangles with hippocampal and cortical atrophy.

Last reviewed 21 May 2026 - MedicoMedics editorial team

Hippocampal atrophy in Alzheimer disease

Pathophysiology

Amyloid-beta 42 (from APP via beta-/gamma-secretase) triggers hyperphosphorylated tau and neuronal loss. Risk genes: APOE-e4, APP, PSEN1/2.

Sources: NIA-AA Framework (Alzheimers Dement 2018;14:535); CLARITY-AD (NEJM 2023;388:9)

Presentation

Insidious short-term memory loss, word-finding difficulty, visuospatial deficits progressing to loss of ADLs. Apathy, agitation common.

Diagnosis

MoCA/MMSE; MRI hippocampal atrophy. CSF: low Abeta42, high phospho-tau. Plasma p-tau217 or amyloid-PET confirm biomarker diagnosis.

Management

Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild-moderate; memantine (NMDA antagonist) added moderate-severe. Anti-amyloid mAbs (lecanemab, donanemab) for early biomarker-positive AD - monitor for ARIA.

Sample USMLE-style MCQs

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Question 1

A 72-year-old with 2 years memory loss, MMSE 22, hippocampal atrophy. Best initial drug?

Question 2

What does lecanemab bind?

Question 3

Strongest late-onset AD risk gene?

Question 4

AD patient on lecanemab develops confusion and MRI hyperintensities. Diagnosis?

Question 5

Feature of NPH rather than AD?

References

Primary guidelines and peer-reviewed sources used for this entry. Reviewed 21 May 2026 by MedicoMedics editorial team.

  1. NIA-AA Framework (Alzheimers Dement 2018;14:535)
  2. CLARITY-AD (NEJM 2023;388:9)

Frequently asked

What is ARIA?

Amyloid-related imaging abnormalities (oedema, microhaemorrhage) with anti-amyloid mAbs, esp APOE-e4 homozygotes.

Best plasma biomarker?

p-tau217 - high sensitivity for amyloid.

First-line drug?

Donepezil.

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