Although the beneficial effects of physical activity (PA) on memory and executive function are well established in older adults, little is known about the relationship between PA and brain microstructure and the contributions of physical functional limitations and chronic diseases. This study examined whether higher PA would be longitudinally associated with greater microstructural integrity in memory- and executive function-related networks and whether these associations would be independent of physical function and chronic diseases.

Diffusion tensor imaging was obtained in 2006–2008 in 276 participants (mean age = 83.0 years, 58.7% female, 41.3% black) with PA (sedentary, lifestyle active, and exercise active) measured in 1997–1998. Gait speed, cognition, depressive symptoms, cardiovascular and pulmonary diseases, hypertension, stroke, and diabetes were measured at both time points. Mean diffusivity and fractional anisotropy were computed from normal-appearing gray and white matter in frontoparietal and subcortical networks. Moderating effects of physical function and chronic diseases were tested using hierarchical regression models.

Compared with the sedentary, the exercise active group had lower mean diffusivity in the medial temporal lobe and the cingulate cortex (β, p values: −.405, .023 and −.497, .006, respectively), independent of age, sex, and race. Associations remained independent of other variables, although they were attenuated after adjustment for diabetes. Associations between PA and other neuroimaging markers were not significant.

Being exercise active predicts greater memory-related microstructural integrity in older adults. Future studies in older adults with diabetes are warranted to examine the neuroprotective effect of PA in these networks.