Physical Activity Attenuates Age-Related Biomarker Alterations in Preclinical AD

Ozioma Okonkwo, Stephanie Schultz, Jennifer Oh, Jordan Larson, Dorothy Edwards, Dane Cook, Rebecca Koscik, Catherine L. Gallagher, N. Maritza Dowling, Cynthia Carlsson, Barbara Bendlin, Asenath LaRue, Howard Rowley, Brad Christian, Sanjay Asthana, Bruce Hermann, Sterling Johnson, and Mark Sager

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.


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