Saki Nakashima, Kenichiro Sato, Yoshiki Niimi, Ryoko Ihara, Kazushi Suzuki, Atsushi Iwata, Wataru Satake, Takeshi Iwatsubo, Japanese Alzheimer's Disease Neuroimaging Initiative
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.