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

Abstract

AbstractBackgroundPhysical 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.Method57 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.ResultHigher Fitbit calories burned and step count correlated with lower levels of GFAP (r = ‐0.33 to ‐0.54, p<0.01) and NfL (r = ‐0.36 to ‐0.45, p<0.01). After controlling for age, average calories burned remained significantly associated with GFAP (β = ‐0.40, p< 0.01) and NfL (β = ‐0.30, p<0.01), while the associations attenuated between total steps with GFAP (β = ‐0.14, p = 0.31) and NfL (β = ‐0.17, p = 0.18). Effect sizes for all models remained similar further adjusting for amyloid PET centiloid levels (calories burned: GFAP: β = ‐0.44, p< 0.01; NfL: β = ‐0.29, p = 0.06; and total steps: GFAP: β = ‐0.23, p = 0.14; NfL: β = ‐0.26, p = 0.10). Interactions between Fitbit metrics and amyloid PET centiloids were not statistically significant for GFAP or NFL (ps >0.5).ConclusionGreater step count and, particularly, calories burned was associated with markers of lower astrocytic inflammation and axonal degeneration in older adults. Our results demonstrate that calories burned may have a more direct (and positive) impact on axonal and astrocytic health in comparison to overall movement. Consequently, these findings suggest higher intensity calorie burning activities may be an important brain health recommendation for older adults. Careful understanding which aspects of physical activity map onto which biological pathways of brain health could inform more precise exercise recommendations and intervention.