Neurology. 2014 Nov 4;83(19):1753-60.
Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer’s disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred and seventeen enrollees in the Wisconsin Registry for Alzheimer’s Prevention underwent T1 MRI; a subset also underwent PiB-PET (n=186) and FDG-PET (n=152) imaging. Participants’ responses on a self-report measure of current physical activity were used to classify them as either Physically Active or Physically Inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age*physical activity interactions for amyloid-β burden (p=.015), glucose metabolism (p=.015), and hippocampal volume (p=.025) such that, with advancing age, Physically Active individuals exhibited less biomarker alterations compared with the Physically Inactive. Similar age*physical activity interactions were also observed on cognitive domains of Immediate Memory (p=.042) and Visuospatial Ability (p=.016). In addition, the Physically Active group had higher scores on Speed & Flexibility (p=.002) compared with the Inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life.