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

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSEducational attainment is a key proxy of cognitive reserve (CR), but whether its association with cognition persists after accounting for multimodal brain pathology remains unclear. METHODSData 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 Alzheimers disease biomarkers. Education was examined in both cohorts. A multidimensional CR questionnaire was also examined in CIMA-Q. RESULTSHigher 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 PREVENT-AD. DISCUSSIONFindings support a CR framework in which education relates to better cognition despite pathology, while effects on decline are limited and domain-specific.