Physical activity attenuates age-related biomarker alterations in preclinical AD




Ozioma C. Okonkwo, PhD; Stephanie A. Schultz, BSc; Jennifer M. Oh, BSc; Jordan Larson, BA; Dorothy Edwards, PhD; Dane Cook, PhD; Rebecca Koscik, PhD; Catherine L. Gallagher, MD; N.M. Dowling, PhD; Cynthia M. Carlsson, MD, MS; Barbara B. Bendlin, PhD; Asenath LaRue, PhD; Howard A. Rowley, MD; Brad T. Christian, PhD; Sanjay Asthana, MD; Bruce P. Hermann, PhD; Sterling C. Johnson, PhD; Mark A. Sager, MD


Objective: To examine whether engagement in physical activity might favorably alter the age- dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults.

Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer’s Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n 5 186) and 18F-fluorodeoxyglucose–PET (n 5 152) 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 3 physical activity interactions for b-amyloid burden (p 5 0.014), glucose metabolism (p 5 0.015), and hippocampal volume (p 5 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age 3 physical activity interactions were also observed on cognitive domains of Immediate Memory (p 5 0.042) and Visuospatial Ability (p 5 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p 5 0.002) 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.


November 4, 2014

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