Associations of salivary cortisol with cognitive function in the Baltimore memory study

Arch Gen Psychiatry. 2007 Jul;64(7):810-8. doi: 10.1001/archpsyc.64.7.810.


Context: The stress responses of the hypothalamic-pituitary-adrenal axis can produce adverse effects on the brain. Previous studies have concluded that an elevated level of cortisol is a risk factor for cognitive dysfunction and decline in aging but have been limited by sex exclusion, restricted cognitive batteries, and small sample sizes.

Objective: To examine associations among salivary cortisol metrics and cognitive domain scores in an urban adult population.

Design, setting, and participants: A cross-sectional analysis was conducted using data from a longitudinal study involving 1140 Baltimore, Maryland, residents aged 50 to 70 years. Four salivary cortisol samples were obtained from 967 participants across 1 study visit (before, during, and after cognitive testing as well as at the end of the visit) from which 7 cortisol metrics were created. We examined associations of cortisol metrics with cognitive performance using multiple linear regression.

Main outcome measures: Performance on 20 standard cognitive tests was measured and combined to form summary measures in 7 domains (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction).

Results: Higher levels of pretest and mean cortisol as well as the area under the curve of cortisol over the study visit were associated with worse performance (P < .05) in 6 domains (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, and visual memory). For instance, an interquartile range increase in the area under the curve was equivalent to a decrease in the language score expected from an increase in 5.6 (95% confidence interval, 4.2-7.1) years of age.

Conclusions: Elevated cortisol was associated with poorer cognitive function across a range of domains in this large population-based study. We believe the findings are consistent with the hypothesis that hypothalamic-pituitary-adrenal axis dysregulation may be a risk factor for poorer cognitive performance in older persons.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Area Under Curve
  • Baltimore
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / epidemiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuropsychological Tests / statistics & numerical data
  • Risk Factors
  • Saliva / chemistry*
  • Smoking / epidemiology
  • Smoking / psychology
  • Stroke / diagnosis
  • Stroke / epidemiology
  • Urban Population


  • Hydrocortisone