382 Ch 381. Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI)

AD = most common cause of dementia (60-80%) + leading cause of disability + death in elderly; pathology: amyloid-β plaques (Aβ42 oligomers) + neurofibrillary tangles (hyperphosphorylated tau) + neuronal loss + cholinergic deficit + Braak staging (entorhinal → hippocampal → temporal/parietal → frontal/occipital)；clinical: insidious + progressive memory loss (recent > remote) + anomic language + visuospatial deficits + executive dysfunction + behavioral/psychological symptoms of dementia (BPSD) in advanced stages；risk factors: age (top), APOE ε4 (1 copy 3x, 2 copies 8-12x), Down syndrome, low education, CV risk factors, head trauma, depression, sleep disorders；diagnosis (NIA-AA 2024 revised) — biological framework based on biomarkers (Aβ + tau) rather than clinical syndrome alone; MCI = cognitive decline beyond aging but without functional impairment, may or may not progress to dementia；REVOLUTION 2023-2024: lecanemab (Leqembi) FDA Jan 2023 (full Jul 2023) anti-amyloid mAb for early AD (MCI + mild dementia) — modest cognitive benefit + ARIA risk; donanemab (Kisunla) FDA July 2024 — efficient amyloid clearance, longer dosing intervals；symptomatic — cholinesterase inhibitors (donepezil, rivastigmine, galantamine) + memantine (NMDA antagonist)；plasma biomarkers (p-tau 217, Aβ42/40, GFAP, NfL) emerging。