Late‐life physical activity relates to brain tissue synaptic integrity markers in older adults

Abstract Introduction Physical activity (PA) is widely recommended for age‐related brain health, yet its neurobiology is not well understood. Animal models indicate PA is synaptogenic. We examined the relationship between PA and synaptic integrity markers in older adults. Methods Four hundred four decedents from the Rush Memory and Aging Project completed annual actigraphy monitoring (Mean visits = 3.5±2.4) and post mortem evaluation. Brain tissue was analyzed for presynaptic proteins (synaptophysin, synaptotagmin‐1, vesicle‐associated membrane proteins, syntaxin, complexin‐I, and complexin‐II), and neuropathology. Models examined relationships between late‐life PA (averaged across visits), and timing‐specific PA (time to autopsy) with synaptic proteins. Results Greater late‐life PA associated with higher presynaptic protein levels (0.14 < β < 0.20), except complexin‐II (β = 0.08). Relationships were independent of pathology but timing specific; participants who completed actigraphy within 2 years of brain tissue measurements showed largest PA‐to‐synaptic protein associations (0.32 < β < 0.38). Relationships between PA and presynaptic proteins were comparable across brain regions sampled. Discussion PA associates with synaptic integrity in a regionally global, but time‐linked nature in older adults.