Abstract
INTRODUCTION: Physical activity (PA) is associated with better cognitive and brain health. However, it remains unclear whether PA relates to accumulation of disease pathology ("resistance") or indirectly moderates adverse effects of pathology on cognition ("cognitive resilience"). METHODS: Five hundred thirteen Rush Memory and Aging Project (MAP) decedents completed longitudinal actigraphy monitoring, cognitive testing, and neuropathological examination. Cross-sectional models tested the relationship between average PA and pathology, and the moderating effect of baseline PA on the association between pathology and cognition. Longitudinal models examined whether changes in PA moderated associations between pathology and cognition. RESULTS: PA was negatively associated with Lewy body disease (LBD), but positively associated with Alzheimer's disease (AD) burdens. Baseline PA attenuated the association between cerebrovascular pathology and cognition, whereas longitudinal change in PA attenuated associations between AD, cerebral amyloid angiopathy, TAR DNA-binding protein 43, and atherosclerosis on cognitive decline. DISCUSSION: Whereas PA relates to "cognitive resilience" against cerebrovascular disease, AD, and other neuropathologies, "resistance" effects were limited.