Abstract Body: Introduction: Physical activity (PA) has been identified as a protective factor for dementia, but the mechanisms linking PA to brain health are unclear. To elucidate potential pathways linking PA to brain health, we tested the hypothesis that higher levels of late-life PA are associated with a lower burden of Alzheimer’s disease (AD) pathology, cerebrovascular disease, and neurodegeneration measured through brain imaging and plasma biomarkers.

Methods: ARIC-NCS participants without dementia in 2011-13 and with measures of PA, 3T brain magnetic resonance imaging (MRI), and stored plasma samples were examined (n=1,771; mean age: 76.5 years; 40.5% male; 27.6% Black). Participants were classified as meeting or not meeting 2018 aerobic PA guidelines based on a standardized interviewer-administered questionnaire. MRI biomarkers included white matter hyperintensity (WMH) volume (cm³), total brain volume (TBV) (cm³), and cortical thickness (CT) (mm). Plasma biomarkers of the ratio of amyloid beta 42 to 40 (Aβ42/Aβ40), phosphorylated Tau-181 (p-Tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured using Quanterix Simoa immunoassays. All biomarkers were standardized to measures in 2011-13 to facilitate comparisons. Covariate-adjusted linear regression models estimated cross-sectional associations of PA with MRI or plasma biomarkers. Covariate-adjusted linear mixed effects models quantified associations of PA with the 5-year rate of change in a subset of participants with MRI (n=669) or plasma (n=651) biomarkers at both baseline and follow-up from 2011-19 (median follow-up: 5.4 years).

Results: Meeting versus not meeting aerobic PA guidelines was cross-sectionally associated with lower volumes of WMH (β = -0.16, 95% CI: -0.25, -0.07), higher TBV (β = 0.09; 95% CI: 0.05, 0.13), and lower plasma NfL (β = -0.102, 95% CI: -0.184, -0.021) (Figure). Late-life PA was not associated with 5-year rates of change in MRI or plasma biomarkers.

Conclusions: Late-life PA was cross-sectionally associated with less neurodegeneration and cerebrovascular disease. Associations with 5-year changes in imaging and plasma biomarkers of AD pathology, cerebrovascular disease, or neurodegeneration were not statistically supported. Longitudinal biomarker studies with wearable devices that quantify other daily intensity-based movement metrics (e.g., light PA) and larger sample sizes are needed to further examine mechanisms linking PA to brain health.