Abstract 13148: Cardiometabolic Risk Factors Partially Mediate the Association of Physical Inactivity With MRI Markers of Brain Aging

Abstract

Introduction: Physical inactivity is associated with a higher risk of dementia, and has also been associated with unfavorable brain morphology. It is also clear that cardiometabolic risk factors accelerate the brain aging process. Hypothesis: Cardiometabolic risk factors mediate the association of physical inactivity with unfavorable brain morphology. Methods: Our investigation included participants from the Third Generation (exam 2) and Offspring (exam 9) cohorts of the Framingham Heart Study who wore an accelerometer for &gte10 hours on &gte3 days (to measure moderate to vigorous physical activity [MVPA] and steps walked per day), underwent brain MRI scans, and had no dementia, stroke, or missing cardiometabolic risk factor data (n=2416, 54% women, mean age 54.1 years). Higher levels of brain peak width of skeletonized mean (white matter) diffusivity, higher free water, and lower total cerebral brain volume were measured by MRI as markers of brain aging. We examined mediation by the 2017 revised version of the Framingham Stroke Risk Profile (FSRP, using weights for age, prevalent cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of MVPA and steps with brain volume, white matter diffusivity, and free water, adjusting for age, age-squared, sex, wear time, smoking status (for HOMA-IR mediation analysis only), cohort, time from exam to MRI, and season of exam. Results: The associations of lower MVPA and steps with lower brain volume, higher white matter diffusivity, and higher free water were partially mediated through FSRP, accounting for 14.1-25.7% (p&lt0.05) of the total association of physical inactivity with brain aging. The association of fewer steps (but not MVPA) with lower brain volume was mediated by HOMA-IR (20.1% of the total association, p&lt0.05). Conclusions: Our results suggest that the associations of physical inactivity with lower brain volume, poorer white matter microstructure and aggregation of free water in the extracellular compartments of the brain are partially mediated by cardiometabolic risk factors.