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November 04, 2014; 83 (19) Article

Physical activity attenuates age-related biomarker alterations in preclinical AD

Ozioma C. Okonkwo, Stephanie A. Schultz, Jennifer M. Oh, Jordan Larson, Dorothy Edwards, Dane Cook, Rebecca Koscik, Catherine L. Gallagher, N.M. Dowling, Cynthia M. Carlsson, Barbara B. Bendlin, Asenath LaRue, Howard A. Rowley, Brad T. Christian, Sanjay Asthana, Bruce P. Hermann, Sterling C. Johnson, Mark A. Sager
First published October 8, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000964
Ozioma C. Okonkwo
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.
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Stephanie A. Schultz
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.
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Jennifer M. Oh
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.
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Jordan Larson
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.
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Dorothy Edwards
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.
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Dane Cook
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.
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Rebecca Koscik
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.
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Catherine L. Gallagher
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.
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N.M. Dowling
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.
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Cynthia M. Carlsson
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.
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Barbara B. Bendlin
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.
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Asenath LaRue
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.
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Howard A. Rowley
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.
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Brad T. Christian
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.
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Sanjay Asthana
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.
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Bruce P. Hermann
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.
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Sterling C. Johnson
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.
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Mark A. Sager
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.
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Full PDF
Citation
Physical activity attenuates age-related biomarker alterations in preclinical AD
Ozioma C. Okonkwo, Stephanie A. Schultz, Jennifer M. Oh, Jordan Larson, Dorothy Edwards, Dane Cook, Rebecca Koscik, Catherine L. Gallagher, N.M. Dowling, Cynthia M. Carlsson, Barbara B. Bendlin, Asenath LaRue, Howard A. Rowley, Brad T. Christian, Sanjay Asthana, Bruce P. Hermann, Sterling C. Johnson, Mark A. Sager
Neurology Nov 2014, 83 (19) 1753-1760; DOI: 10.1212/WNL.0000000000000964

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  • Physical activity attenuates age-related biomarker alterations in preclinical AD - March 03, 2015
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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 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.

GLOSSARY

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

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received April 15, 2014.
  • Accepted in final form August 6, 2014.
  • © 2014 American Academy of Neurology
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