title: Physical activity attenuates age-related biomarker alterations in preclinical AD.
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.
authors.affiliation: 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.
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
authors.affiliation: 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.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schultz
authors.affiliation: 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.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Oh
authors.affiliation: 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.
authors.forename: Jordan
authors.initials: J
authors.lastname: Larson
authors.affiliation: 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.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Edwards
authors.affiliation: 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.
authors.forename: Dane
authors.initials: D
authors.lastname: Cook
authors.affiliation: 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.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Koscik
authors.affiliation: 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.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
authors.affiliation: 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.
authors.forename: N M
authors.initials: NM
authors.lastname: Dowling
authors.affiliation: 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.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: 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.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: 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.
authors.forename: Asenath
authors.initials: A
authors.lastname: LaRue
authors.affiliation: 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.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.affiliation: 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.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: 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.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: 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.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
authors.affiliation: 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.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013844:Thiazoles; D014796:Visual Perception
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18