Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia.

OBJECTIVE: We investigated the associations of morning and evening salivary cortisol levels with regional brain volumes and cognitive functioning in community-dwelling older persons without dementia. METHOD: From the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons without dementia (age 76 ± 5 years, 58% women) who had 1.5T brain MRI, assessment of cognitive functioning, and saliva collected at home 45 minutes after awakening and at night. Linear regression analysis was used to estimate the cross-sectional relationship among cortisol levels, brain volumes, and cognitive functioning, adjusting for covariates. RESULTS: Higher evening cortisol was associated with smaller total brain volume (highest vs lowest tertile -16.0 mL; 95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education, intracranial volume, smoking, steroid use, white matter lesions, and brain infarcts on MRI). The smaller volumes were observed in all brain regions, but were significantly smaller in gray matter than in white matter regions. Poorer cognitive functioning across all domains was also associated with higher evening cortisol. Higher levels of morning cortisol were associated with slightly greater normal white matter volume and better processing speed and executive functioning, but not with gray matter volume or with memory performance. CONCLUSIONS: In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function. Understanding these differential associations may aid in developing strategies to reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late-life cognitive impairment.