Physical activity attenuates age-related biomarker alterations in preclinical AD

Neurology. 2014 Nov 4;83(19):1753-60. doi: 10.1212/WNL.0000000000000964. Epub 2014 Oct 8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / prevention & control
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Brain / anatomy & histology
  • Brain / diagnostic imaging
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Motor Activity / physiology*
  • Neuroimaging
  • Neuropsychological Tests
  • Radionuclide Imaging
  • Risk Factors
  • Surveys and Questionnaires
  • Thiazoles
  • Visual Perception


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Thiazoles
  • Fluorodeoxyglucose F18