Physical Activity Relates to Lower Astrocytic Activation and Axonal Breakdown in Clinically Normal Older Adults

Background Physical activity is associated with >30% reduced risk of dementia. However, the biological mechanisms underlying exercise as a protective factor against cognitive decline remain unclear. Astrocytic activation and axonal breakdown, as measured by plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), respectively, are pathways disrupted early in cognitive aging and neurodegenerative disease. We aimed to examine whether an objective measure of physical activity (FitbitTM) related to plasma levels of GFAP and NfL in clinically normal older adults. Method 57 clinically normal older adults completed 30‐day FitbitTM Flex2 monitoring (average daily steps and calories burned estimated) and a blood draw with plasma analyzed via Quanterix SIMOA for GFAP and NfL. A subset (n = 48) completed an amyloid PET scan (18F‐AV45 or 11C‐PIB). Pairwise correlations and linear regression models adjusting for age and cerebral amyloid burden evaluated the associations among Fitbit metrics and plasma markers of interest. Result Higher Fitbit calories burned and step count correlated with lower levels of GFAP (r = ‐0.33 to ‐0.54, p