382.2 🩺 國考版

382.2.1 高頻考點

382.2.1.1 Epidemiology

  • 60-80% of dementia
  • Most common cause
  • Age strongest risk factor

382.2.1.2 Pathology

  • Aβ plaques
  • Tau tangles
  • Neuronal loss
  • Cholinergic deficit (nucleus basalis)

382.2.1.3 APOE ε4

  • 1 copy: 3x risk
  • 2 copies: 8-12x risk
  • Highest ARIA risk with anti-amyloid

382.2.1.4 Clinical Hallmark

  • Episodic memory loss (recent > remote)
  • Insidious, progressive

382.2.1.5 Atypical AD

  • Logopenic primary progressive aphasia
  • Posterior cortical atrophy
  • Frontal variant

382.2.1.6 NIA-AA 2024 Revision

  • Biological diagnosis (biomarkers)
  • Preclinical, MCI due to AD, dementia due to AD

382.2.1.7 Biomarkers

CSF: - Aβ42 ↓ - Aβ42/40 ratio ↓ - Total tau ↑ - p-tau 181, 217 ↑

Imaging: - Amyloid PET - Tau PET - FDG-PET (temporoparietal hypo) - MRI (hippocampal atrophy)

Plasma: - p-tau 217 (most accurate) - Aβ42/40 - GFAP, NfL

382.2.1.8 Cognitive Tests

  • MMSE 0-30 (mild < 24)
  • MoCA 0-30 (more sensitive for MCI)

382.2.1.9 Cholinesterase Inhibitors

  • Donepezil, rivastigmine, galantamine
  • For mild-moderate AD
  • Modest benefit
  • GI side effects

382.2.1.10 Memantine

  • NMDA antagonist
  • Moderate-severe
  • Combine with ChEI

382.2.1.11 Lecanemab (Leqembi) FDA 2023

  • Anti-amyloid mAb (anti-protofibril)
  • Early AD
  • IV q2 weeks
  • Slowed decline ~ 27%
  • ARIA-E + ARIA-H risk
  • APOE ε4 homozygous highest ARIA risk

382.2.1.12 Donanemab (Kisunla) FDA July 2024

  • Anti-amyloid (pyroglutamate Aβ)
  • IV monthly
  • Faster clearance
  • TRAILBLAZER-ALZ 2
  • Treatment until amyloid cleared

382.2.1.14 Brexpiprazole for AD Agitation

  • FDA 2023
  • Atypical antipsychotic
  • For BPSD

382.2.1.15 Aducanumab

  • Withdrawn 2024 (controversial approval)

382.2.1.16 MCI

  • Beyond aging
  • No functional impairment
  • Amnestic MCI most likely AD
  • 10-15% per year progress

382.2.1.17 Modifiable Risk Factors (Lancet 2024: 14)

  • HTN, DM, obesity, smoking, dyslipidemia
  • Low education
  • Head trauma
  • Depression
  • Hearing loss
  • Social isolation
  • Physical inactivity
  • Sleep disorders
  • Air pollution
  • Alcohol
  • Vision loss (new in 2024 commission)

382.2.2 Specific Issues

382.2.2.1 Down Syndrome and AD

  • Almost all develop AD pathology by age 40
  • Earlier onset
  • Different presentation (executive, behavioral first)
  • Screening recommended

382.2.2.2 Familial AD (Early-Onset, < 65)

  • APP, PSEN1 (most common), PSEN2
  • Autosomal dominant
  • Onset 30s-50s
  • DIAN study (Dominantly Inherited AD Network)

382.2.2.3 CAA (Cerebral Amyloid Angiopathy)

  • Often co-exists with AD
  • Lobar hemorrhages
  • Microbleeds on SWI
  • Caution with anticoagulation

382.2.2.4 Cognitive Reserve

  • Higher education + cognitive engagement
  • Reserve against clinical expression
  • Despite pathology

382.2.2.5 Hearing Loss Treatment

  • Hearing aids reduce dementia risk
  • ACHIEVE trial 2023