HIGH LIFESPAN COGNITIVE RESERVE IS ASSOCIATED WITH A REDUCED DEMENTIA RISK, INDEPENDENTLY OF BRAIN PATHOLOGIES

Abstract

Cognitive reserve (CR) has been proposed as compensatory mechanisms to cope with brain damages. However, evidence on the association between lifespan CR with dementia is limited, and the role of brain pathologies in the association is unknown. Within the Rush Memory and Aging Project (MAP), 1638 dementia-free older adults (mean age=79) were followed for up to 20 years to detect incident dementia cases. Information on CR factors (education, cognitive activities at early, mid- and late-life, and social activities in late life) was obtained at the study entry. Based on these factors, lifespan CR was captured by a latent variable which was divided into tertiles: lowest, middle and highest. During the follow-up, 633 participants died and underwent neuropathologic evaluations for Alzheimer's disease and other brain pathologies. Data were analyzed using structural equation model, Cox model and logistic regression. During the follow-up, 386 participants developed dementia (357 Alzheimer's dementia). The multi-adjusted hazards ratios (HR, 95% CI) of dementia were 0.77 (0.59–0.99, p=0.048) for middle CR, and 0.61 (0.47–0.81) for highest CR compared to lowest CR. The risk reduction by highest CR was greater in APOE ε4 carriers than non-ε4 carriers (attributable proportion due to interaction=0.43, 95% CI 0.16–0.71). In autopsied participants, middle and highest CR were not related to the burden of AD pathologies and most of other brain pathologies comparing to lowest CR. The association between high CR and dementia remained significant (HR=0.60, 95% CI 0.42–0.86) after additional adjustment for the pathologies. Middle to highest lifespan CR is associated with a reduced dementia risk, independent of brain pathologies. High CR may mitigate APOE ɛ4 related dementia risk.