January 2023 Bonus: Lecanemab in Early Alzheimer’s Disease
The issue
In the 18‑month, 1,795‑patient Clarity AD trial, the anti‑amyloid antibody lecanemab slowed early‑Alzheimer progression: Clinical Dementia Rating–Sum of Boxes scores rose 1.21 points on lecanemab versus 1.66 on placebo — a 27 % smaller decline (difference –0.45). Key cognitive and daily‑function scales all favored the drug, and brain‑amyloid PET fell by 59 centiloids relative to placebo.
What do I need to know?
Participants received 10 mg/kg IV every two weeks. Infusion reactions (26 %) and amyloid‑related imaging abnormalities (ARIA‑E 12.6 %, ARIA‑H 17.3 %) were common but usually mild and transient; symptomatic ARIA‑E occurred in 2.8 % of treated patients. Benefits appeared by three months and persisted through 18 months, but longer studies are under way.
Potential risk of amyloid‑related cognitive decline
Cognitively normal adult ≥ 60 with no amyloid testing.
Recommended Actions
Maintain heart‑healthy habits (exercise, blood‑pressure and cholesterol control, adequate sleep).
Review family history; discuss non‑invasive memory screens and whether an amyloid PET or CSF test is warranted.
Revisit risk annually, since 20–40 % of asymptomatic seniors eventually accumulate amyloid.
Imminent risk of cognitive decline
Amyloid‑positive on PET or CSF but no measurable impairment (preclinical Alzheimer’s).
Recommended Actions
Ask about prevention trials or future access to plaque‑clearing antibodies once regulators approve them for this stage.
Track memory with annual tests (e.g., MoCA or PACC).
Optimize vascular risk factors and engage in regular physical and cognitive activity.
Confirmed early Alzheimer’s disease
Mild cognitive impairment or mild dementia with elevated amyloid (CDR 0.5–1).
Recommended Actions
Discuss eligibility for lecanemab (bi‑weekly IV infusions, ApoE ε4 carriers have higher ARIA risk).
Arrange baseline MRI; repeat scans at ~3 and 6 months to monitor ARIA.
Combine treatment with cognitive‑rehabilitation, safety planning (driving, finances), and caregiver education.
What can I do?
Ask the clinician, “Am I at potential, imminent, or confirmed risk, and would lecanemab’s benefits outweigh its infusion burden and ARIA risk for me?” Bring any brain‑scan reports, cognitive‑test scores, and a list of medications. If therapy starts, keep infusion dates consistent, record side‑effects (headache, visual changes), and schedule follow‑up MRIs. Caregivers can help track appointments, watch for confusion or dizziness after infusions, and ensure home safety measures are in place as cognition changes.
