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

Raeesi, S.; Metz, A.; Chadwick, K. M.; Zeighami, Y.; The PREVENT-AD Research Group, ; The Consortium for the Early Identification of Alzheimers Disease - Quebec (CIMA-Q), ; Morrison, C.; Dadar, M.

2026-05-12 neurology
10.64898/2026.05.07.26352659 medRxiv
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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.

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