PET-based evaluation of short-term amyloid-β clearance and predictive factors in real-world Alzheimer's disease patients treated with lecanemab

Background Alzheimer's disease (AD) is a common progressive neurodegenerative disorder. Lecanemab, an anti-amyloid-β (Aβ) monoclonal antibody, is approved for AD treatment, but real-world efficacy and optimal PET application strategies remain incompletely defined. Objective To investigate lecanemab's Aβ clearance efficacy, identify predictors of response, and optimize PET application strategies. Methods A retrospective analysis of Aβ PET-positive AD patients treated with lecanemab for 6–8 months. Paired t-tests evaluated standardized uptake value ratios (SUVR) and cognitive changes; Cohen's Kappa assessed visual-quantitative agreement. Exploratory analyses included partial correlation, regression, and Fisher's exact test. Results Thirty-eight patients were included. Statistically significant Centiloid (CL) reduction occurred post-treatment (mean difference = 29.39 ± 22.31, p < 0.001), without Mini-Mental State Examination/Montreal Cognitive Assessment or tau PET changes. Twelve patients achieved a CL < 24.1, and 5 were visually negative. Visual-quantitative agreement was fair to poor (positivity Kappa = 0.205; efficacy Kappa = 0.253). Baseline CL, treatment cycles, and SUVRtau were screened by univariate regression (p < 0.05) and entered into a multivariate model (F = 13.693, p < 0.001, adjusted R 2 = 0.507). Baseline CL (standardized-β = 0.594, p < 0.001) and treatment cycles (standardized-β = 0.285, p = 0.022) were independent positive predictors; SUVRtau showed marginal negative association (standardized-β = −0.238, p = 0.052). Conclusions Lecanemab was associated with statistically significant amyloid clearance. Baseline amyloid burden and treatment exposure predicted greater clearance; tau showed attenuating trend. Visual-quantitative discordance supports a hybrid PET pathway: visual screening for inclusivity, serial CL quantification for monitoring, and combined assessment for low-CL patients.