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Physical activity attenuates age-related biomarker alterations in preclinical AD


Okonkwo, O. C., Schultz, S. A., Oh, J. M., Larson, J., Edwards, D., Cook, D., Koscik, R., Gallagher, C. L., Dowling, N. M., Carlsson, C. M., Bendlin, B. B., LaRue, A., Rowley, H. A., Christian, B. T., Asthana, S., Hermann, B. P., Johnson, S. C., Sager, M. A.


Neurology, Volume: 83, No.: 19, Pages.: 1753-1760

Year of Publication



Objective: To examine whether engagement in physical activity might favorably alter the agedependent 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 3 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. (PsycINFO Database Record (c) 2015 APA, all rights reserved). (journal abstract)

Bibtex Citation

@article{Okonkwo_2014, doi = {10.1212/wnl.0000000000000964}, url = {}, year = 2014, month = {oct}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {83}, number = {19}, pages = {1753--1760}, author = {O. C. Okonkwo and S. A. Schultz and J. M. Oh and J. Larson and D. Edwards and D. Cook and R. Koscik and C. L. Gallagher and N. M. Dowling and C. M. Carlsson and B. B. Bendlin and A. LaRue and H. A. Rowley and B. T. Christian and S. Asthana and B. P. Hermann and S. C. Johnson and M. A. Sager}, title = {Physical activity attenuates age-related biomarker alterations in preclinical {AD}}, journal = {Neurology} }


age differences, age related biomarker alterations, alzheimer’s disease, at risk populations, cognitive changes, cognitive impairment, exercise, pathophysiology, physical activity

Countries of Study


Type of Outcomes




Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population