Abstract

This study examines the relationship of engagement in different lifestyle activities to connectivity in large-scale functional brain networks, and whether network connectivity modifies cognitive decline, independent of brain amyloid levels. Participants (N = 153, mean age = 69years, including N = 126 with amyloid imaging) were cognitively normal when they completed resting-state functional magnetic resonance imaging, a lifestyle activity questionnaire, and cognitive testing. They were followed with annual cognitive tests up to 5years (mean = 3.3years). Linear regressions showed positive relationships between cognitive activity engagement and connectivity within the dorsal attention network, and between physical activity levels and connectivity within the default-mode, limbic, and frontoparietal control networks, and global within-network connectivity. Additionally, higher cognitive and physical activity levels were independently associated with higher network modularity, a measure of functional network specialization. These associations were largely independent of APOE4 genotype, amyloid burden, global brain atrophy, vascular risk, and level of cognitive reserve. Moreover, higher connectivity in the dorsal attention, default-mode, and limbic networks, and greater global connectivity and modularity were associated with reduced cognitive decline, independent of APOE4 genotype and amyloid burden. These findings suggest that changes in functional brain connectivity may be one mechanism by which lifestyle activity engagement reduces cognitive decline.

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