Anti-amyloid monoclonal antibody therapies — lecanemab (Leqembi) and donanemab (Kisunla) — have entered clinical use as disease-modifying treatments for early Alzheimer's disease. The mechanism is direct removal of amyloid plaques through targeted antibodies; the clinical effect is modest but real slowing of cognitive decline (roughly 25-35% reduction in decline rate over 18 months in Phase 3 trials). The 2026 landscape includes established FDA approval, defined candidate criteria, real infrastructure requirements, substantial cost, and ongoing conversation about the risk-benefit balance.
The Phase 3 evidence base. Lecanemab CLARITY-AD trial showed 27% reduction in clinical decline by CDR-SB over 18 months in patients with MCI due to AD or mild AD with confirmed amyloid pathology. Donanemab TRAILBLAZER-ALZ 2 showed similar magnitude effect with somewhat different protocol (treatment-to-target with discontinuation when amyloid clearance achieved). The effect size is modest in absolute terms; it represents the first treatments to alter disease trajectory rather than just symptomatic management.
Candidate selection. Confirmed amyloid pathology (amyloid PET, CSF biomarkers, or increasingly blood-based markers — Stage 23.2). MCI or mild AD by clinical criteria. No major contraindications — uncontrolled hypertension, recent stroke, anticoagulation in some considerations, severe cardiovascular disease. APOE4 status assessment — APOE4 homozygotes (about 2% of population) have substantially elevated risk of ARIA (amyloid-related imaging abnormalities) and may not be candidates or require modified protocols. Patient and family understanding of treatment requirements and possible adverse events.
The treatment protocol and infrastructure requirements. Lecanemab: IV infusion every 2 weeks; ongoing indefinite treatment. Donanemab: IV infusion every 4 weeks; treatment until amyloid clearance achieved (typically 12-18 months). Both require regular MRI monitoring for ARIA (every few weeks initially, then less frequent). Significant infrastructure — infusion center capacity, MRI access, specialty clinician involvement (neurology with anti-amyloid experience), monitoring protocols. Cost is substantial — Medicare coverage exists but with criteria; private insurance variable; out-of-pocket cost can be $25,000+ annually.
ARIA and other side effects. Amyloid-related imaging abnormalities (ARIA) — edema or microhemorrhages on MRI — occur in roughly 10-20% of treated patients; mostly asymptomatic but some symptomatic and rarely severe. APOE4 homozygotes have substantially elevated ARIA risk. Other side effects include infusion reactions. The risk-benefit conversation requires honest discussion of these real adverse events alongside the modest cognitive effect.
The clinical conversation and integrated care. Anti-amyloid therapy is one component of comprehensive MCI/early AD care, not standalone treatment. The Modifiable Twelve factors continue; treatment of mood, anxiety, sleep; family integration; advance care planning; safety considerations. The patient on anti-amyloid therapy is also engaging the full longevity-psychiatry prescription. The decision about whether to pursue anti-amyloid treatment involves multiple variables — disease stage, biomarker status, candidate suitability, infrastructure access, patient and family understanding, financial considerations. The discipline is to engage anti-amyloid therapy as a real but modest disease-modifying option, coordinate with appropriate specialty care, integrate with broader longevity-psychiatry work, and support patients and families through what is a substantial clinical and life decision.