Ozioma C Okonkwo1, Stephanie A Schultz2, Jennifer M Oh2, Jordan Larson2, Dorothy Edwards2, Dane Cook2, Rebecca Koscik2, Catherine L Gallagher2, N M Dowling2, Cynthia M Carlsson2, Barbara B Bendlin2, Asenath LaRue2, Howard A Rowley2, Brad T Christian2, Sanjay Asthana2, Bruce P Hermann2, Sterling C Johnson2, Mark A Sager2. 1. From the Geriatric Research Education and Clinical Center (O.C.O., S.A.S., J.M.O., J.L., D.C., C.L.G., C.M.C., B.B.B., S.A., S.C.J.), William S. Middleton Memorial VA Hospital, Madison WI; Wisconsin Alzheimer's Institute (O.C.O., D.E., R.K., B.B.B., A.L., S.A., B.P.H., S.C.J., M.A.S.), Wisconsin Alzheimer's Disease Research Center (O.C.O., S.A.S., J.M.O., J.L., D.E., C.L.G., N.M.D., C.M.C., B.B.B., H.A.R., B.T.C., S.A., B.P.H., S.C.J., M.A.S.), Departments of Kinesiology (D.E., D.C.), Neurology (C.L.G.), Biostatistics & Medical Informatics (N.M.D., B.P.H.), Radiology (H.A.R.), and Medical Physics (B.T.C.), University of Wisconsin School of Medicine and Public Health, Madison. ozioma@medicine.wisc.edu. 2. From the Geriatric Research Education and Clinical Center (O.C.O., S.A.S., J.M.O., J.L., D.C., C.L.G., C.M.C., B.B.B., S.A., S.C.J.), William S. Middleton Memorial VA Hospital, Madison WI; Wisconsin Alzheimer's Institute (O.C.O., D.E., R.K., B.B.B., A.L., S.A., B.P.H., S.C.J., M.A.S.), Wisconsin Alzheimer's Disease Research Center (O.C.O., S.A.S., J.M.O., J.L., D.E., C.L.G., N.M.D., C.M.C., B.B.B., H.A.R., B.T.C., S.A., B.P.H., S.C.J., M.A.S.), Departments of Kinesiology (D.E., D.C.), Neurology (C.L.G.), Biostatistics & Medical Informatics (N.M.D., B.P.H.), Radiology (H.A.R.), and Medical Physics (B.T.C.), University of Wisconsin School of Medicine and Public Health, Madison.
Abstract
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 (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-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.
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 (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-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.
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