Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults

Sleep and physical activity levels are both associated with cognitive performance among older adults; however, the brain mechanisms underlying these beneficial relationships remain poorly understood. This study investigated cross-sectional associations of actigraphic estimates of physical activity and sleep with cognition and diffusion imaging-based measures of medial temporal lobe (MTL) gray matter microstructural integrity in adults free of dementia. Participants were 132 older adults from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort study (119 cognitively unimpaired and 13 with mild cognitive impairment; mean age=70.8 years). Multiple linear regression analyses assessed the relationships between total volume of physical activity (TVPA), total sleep time (TST), and sleep efficiency (SE) with cognitive performance and MTL microstructural integrity. Results indicated that greater TVPA and SE were both independently associated with higher hippocampal and parahippocampal microstructure integrity (indicated by lower mean diffusivity) and better visuospatial processing abilities, independent of the volume of these structures and of amyloid burden, measured by positron emission tomography. Additionally, higher hippocampal microstructure statistically mediated the independent associations of physical activity and sleep with visuospatial abilities, independent of MTL volume and Aβ load. These findings suggest that physical activity and sleep are independently associated with cognitive performance, and that hippocampal microstructural integrity may be an underlying mechanism supporting these associations.