Exercise and Alzheimer's disease biomarkers in cognitively normal older adults

Ann Neurol. 2010 Sep;68(3):311-8. doi: 10.1002/ana.22096.


Objective: In addition to the increasingly recognized role of physical exercise in maintaining cognition, exercise may influence Alzheimer's disease (AD) pathology, as transgenic mouse studies show lowered levels of AD pathology in exercise groups. The objective of this study was to elucidate the association between exercise and AD pathology in humans using Pittsburgh compound-B (PIB), amyloid-beta (Abeta)(42), tau, and phosphorylated tau (ptau)(181) biomarkers.

Methods: Sixty-nine older adults (17 males, 52 females) aged 55 to 88 years, were recruited and confirmed to be cognitively normal. A questionnaire on physical exercise levels over the past decade was administered to all. Cerebrospinal fluid samples were collected from 56 participants, and amyloid imaging with PIB was performed on 54 participants.

Results: Participants were classified based on biomarker levels. Those with elevated PIB (p = 0.030), tau (p = 0.040), and ptau(181) (p = 0.044) had significantly lower exercise, with a nonsignificant trend for lower Abeta(42) (p = 0.135) to be associated with less exercise. Results were similar for PIB after controlling for covariates; tau (p = 0.115) and ptau(181) (p = 0.123) differences were reduced to nonsignificant trends. Additional analyses also demonstrated that active individuals who met the exercise guidelines set by the American Heart Association had significantly lower PIB binding and higher Abeta(42) levels with and without controlling for covariates (PIB: p = 0.006 and p = 0.001; Abeta(42): p = 0.042 and p = 0.046). Last, the associations between exercise engagement and PIB levels were more prominent in APOE epsilon 4 noncarriers.

Interpretation: Collectively, these results are supportive of an association between exercise engagement and AD biomarkers in cognitively normal older adults.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Aniline Compounds
  • Apolipoproteins E / genetics
  • Exercise / physiology*
  • Female
  • Geriatric Assessment
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Positron-Emission Tomography / methods
  • Psychiatric Status Rating Scales
  • Risk Factors
  • Thiazoles
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid*


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoproteins E
  • Peptide Fragments
  • Thiazoles
  • amyloid beta-protein (1-42)
  • tau Proteins