Education, Cognitive Reserve, and Brain Pathology in Aging and Alzheimer's Disease: Evidence from Preclinical and Symptomatic Cohorts

INTRODUCTION: Educational attainment is a key proxy of cognitive reserve (CR), but whether its association with cognition persists after accounting for multimodal brain pathology remains unclear. METHODS: Data from PREVENT-AD and CIMA-Q were analyzed using cross-sectional, longitudinal, and residual-based models adjusted for multimodal pathology, including MRI-based white matter hyperintensities and atrophy measures, and plasma Alzheimer's disease biomarkers. Education was examined in both cohorts. A multidimensional CR questionnaire was also examined in CIMA-Q. RESULTS: Higher education was associated with better performance across multiple cognitive domains after accounting for pathology (p < 0.05). The CR composite score showed less consistent associations, and non-education subdomains showed limited added value. Longitudinally, education was more consistently associated with baseline cognitive levels than cognitive change, with executive-function trajectory differences observed in