Longitudinal Association of Total Tau Concentrations and Physical Activity With Cognitive Decline in a Population Sample

JAMA Netw Open. 2021 Aug 2;4(8):e2120398. doi: 10.1001/jamanetworkopen.2021.20398.


Importance: Tau is a brain protein located in neurons and develops abnormally in individuals with Alzheimer disease. New technology is convenient for measuring blood total tau concentrations and provides a unique and increased opportunity for early intervention to slow cognitive decline.

Objective: To evaluate the association of physical activity and total tau concentrations with cognitive decline at baseline and over time.

Design, setting, and participants: The Chicago Health and Aging Project is a population-based cohort study conducted in 4 Chicago communities. Data collection occurred in 3-year cycles between 1993 and 2012. Participants completed in-home interviews. Clinical evaluations, which included blood samples, were performed with a stratified random sample of 1159 participants. Statistical analyses were conducted from October 30, 2020, to May 25, 2021.

Exposures: Physical activity and total serum tau concentrations. Data on physical activity were obtained through self-report items, and a sum of minutes per week was calculated. Little physical activity was defined as no participation in a minimum of 4 of the items on the physical activity measure. Medium activity was defined as participating in less than 150 minutes of physical activity per week, and high activity was defined as participating in 150 minutes or more of physical activity per week.

Main outcomes and measures: The main outcome for this study is global cognitive function, measured through a battery of cognitive tests. The study hypothesis was developed after data were collected.

Results: Of the 1159 participants in the study, 728 were women (63%), and 696 were African American (60%); the mean (SD) age was 77.4 (6.0) years, and the mean (SD) educational level was 12.6 (3.5) years. Participants with high total tau concentrations with medium physical activity had a 58% slower rate of cognitive decline (estimate, -0.028 standard deviation unit [SDU] per year [95% CI, -0.057 to 0.002 SDU per year]; difference, 0.038 SDU per year [95% CI, 0.011-0.065 SDU per year]), and those with high physical activity had a 41% slower rate of cognitive decline (estimate, -0.038 SDU per year [95% CI, -0.068 to -0.009 SDU per year]; difference, 0.027 SDU per year [95% CI, -0.002 to 0.056 SDU per year]), compared with those with little physical activity. Among participants with low total tau concentrations, medium physical activity was associated with a 2% slower rate of cognitive decline (estimate, -0.050 SDU per year [95% CI, -0.069 to -0.031 SDU per year]; difference, 0.001 SDU per year [95% CI, -0.019 to 0.021 SDU per year]), and high physical activity was associated with a 27% slower rate of cognitive decline (estimate, -0.037 SDU per year [95% CI, -0.055 to -0.019 SDU per year]; difference, 0.014 SDU per year [95% CI, -0.007 to 0.034 SDU per year]), compared with little physical activity. Individual tests of cognitive function showed similar results.

Conclusions and relevance: This study suggests that, among participants with both high and low total tau concentrations, physical activity was associated with slower cognitive decline. Results support the potential utility of blood biomarkers in measuring the benefits associated with health behaviors and may contribute to specifying target populations or informing interventions for trials that focus on improving physical activity behavior. Future work should examine the association of total tau concentrations with other health behaviors and physical activity types.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / physiology*
  • Biomarkers / blood*
  • Chicago
  • Cognitive Dysfunction / diagnosis*
  • Cohort Studies
  • Exercise / physiology*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Membrane Proteins / blood*
  • Population Surveillance / methods*
  • Predictive Value of Tests
  • Time Factors


  • Biomarkers
  • Membrane Proteins