RT Journal Article SR Electronic T1 Physical activity attenuates age-related biomarker alterations in preclinical AD JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP 1753 OP 1760 DO 10.1212/WNL.0000000000000964 VO 83 IS 19 A1 Okonkwo, Ozioma C. A1 Schultz, Stephanie A. A1 Oh, Jennifer M. A1 Larson, Jordan A1 Edwards, Dorothy A1 Cook, Dane A1 Koscik, Rebecca A1 Gallagher, Catherine L. A1 Dowling, N.M. A1 Carlsson, Cynthia M. A1 Bendlin, Barbara B. A1 LaRue, Asenath A1 Rowley, Howard A. A1 Christian, Brad T. A1 Asthana, Sanjay A1 Hermann, Bruce P. A1 Johnson, Sterling C. A1 Sager, Mark A. YR 2014 UL http://n.neurology.org/content/83/19/1753.abstract AB 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 = 186) and 18F-fluorodeoxyglucose–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 β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 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.Aβ=β-amyloid; Aβi=β-amyloid indeterminate; AD=Alzheimer disease; DVR=distribution volume ratio; FDG=18F-fluorodeoxyglucose; FH=parental family history; MET=metabolic equivalent; MNI=Montreal Neurological Institute; PCC=posterior cingulate cortex; PiB=11C-Pittsburgh compound B; WRAP=Wisconsin Registry for Alzheimer's Prevention