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

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.

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

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.

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).

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.

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.