Rankings / Cognitive — Nootropics
Anti-amyloid mAbs (lecanemab / donanemab / aducanumab)
Cognitive · Amyloid-beta-targeting monoclonal antibody
Tier C
What this is
Cochrane 2026 (Nonino et al, n=20342 across 17 RCTs): the entire class produces only trivial cognitive (SMD -0.11) and dementia-severity (SMD -0.12) benefit while consistently increasing ARIA-E. Authors conclude 'successful removal of amyloid does not seem to be associated with clinically meaningful effects' and 'future research should focus on other mechanisms of action.' Costly (~$26K/year for lecanemab); requires APOE genotyping (4/4 homozygotes excluded or carefully monitored due to ARIA risk); MRI surveillance every dose.
Mechanism
Monoclonal antibodies bind aggregated amyloid-beta protein in brain (lecanemab targets soluble protofibrils; donanemab targets pyroglutamate amyloid plaques; aducanumab targets fibrillar Aβ) — drive amyloid clearance via Fc-mediated microglial phagocytosis. First disease-modifying drugs for Alzheimer's based on the amyloid hypothesis
Dose & route
Lecanemab 10 mg/kg IV q2 weeks; donanemab 700 mg IV q4 weeks for 3 doses then 1400 mg IV q4 weeks
Citations
- https://doi.org/10.1002/14651858.CD016297
- https://www.nejm.org/doi/full/10.1056/NEJMoa2212948
- https://jamanetwork.com/journals/jama/fullarticle/2820925
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