Therapeutic Time Window of Disease-Modifying Therapy for Early Alzheimer's Disease in Japanese Individuals: Analysis...

Lecanemab and donanemab are recently approved disease-modifying therapies (DMTs) for early Alzheimer's disease (AD), indicating amyloid positivity, with Mini-Mental State Examination (MMSE) requirements. Prior analyses using North American population data suggested that baseline Clinical Dementia Rating-Global Score (CDR-GS) and MMSE may define the "therapeutic time window," but generalizability to Asian populations remains uncertain.

To investigate the duration and predictors of the therapeutic time window, defined as the period until patients with early AD no longer meet eligibility criteria in Japanese patients.

We retrospectively analyzed amyloid-positive participants from Japanese Alzheimer's Disease Neuroimaging Initiative, classified as lecanemab-eligible (MMSE 22-30, n = 129) or donanemab-eligible (MMSE 20-28, n = 143). Kaplan-Meier survival was estimated over 24 months, and Cox proportional-hazards models included age, sex, MMSE, CDR-GS, and baseline diagnosis. Education years, apolipoprotein-E ε4 (APOE-ε4), and CDR-Sum of Boxes (CDR-SB) were tested individually.

At 12 and 24 months, survival probabilities for remaining eligible were 82% and 69% (MCI) versus 51% and 38% (AD) in the lecanemab group, and 92% and 81% (MCI) versus 69% and 52% (AD) in the donanemab group. Baseline CDR-GS of 1 versus 0.5 predicted shorter eligibility for donanemab (HR = 2.50, 95% CI: 1.20-5.21), but not for lecanemab (HR = 0.48, 95% CI: 0.18-1.29). Each one-point increase in MMSE above threshold was protective (HR = 0.67-0.68).

Baseline CDR-GS and MMSE strongly predict the therapeutic time window in Japanese patients, supporting cross-population generalizability and contributing to the management of AD DMTs under resource constraints.