A large, racially diverse study suggests that daily fluctuations in cortisol levels may provide early insight into cognitive aging, though their connection to Alzheimer’s disease remains unclear, according to an Aug. 2 report.
Researchers at Rush University Medical Center in Chicago analyzed salivary cortisol patterns among nearly 4,000 older adults as part of the Chicago Health and Aging Project. The participants included 2,503 Black and 1,392 White individuals who were assessed for cognitive function over a follow-up period of up to 11 years. Saliva samples were collected at three points during a single day—upon waking, in the late afternoon, and in the evening—to measure five indices of daytime hypothalamic-pituitary-adrenal axis activity.
The baseline analysis found that Black participants had lower fluctuations and total daily levels of cortisol compared to White participants. Cognitive assessments showed that Black participants also had lower global cognition scores and experienced faster average rates of cognitive decline than their White counterparts. In a smaller clinical subsample, those who developed Alzheimer’s disease exhibited lower daily cortisol fluctuations and a blunted daytime rhythm.
Fully adjusted analyses indicated that moderate intraday fluctuation in cortisol was significantly associated with higher baseline cognition and slower cognitive decline. Conversely, the highest total daily output of cortisol was linked with lower baseline cognition and more rapid decline. A flatter diurnal slope or attenuated daytime change corresponded with lower baseline cognition scores.
Despite these associations between salivary cortisol indices and cognition, none of the five measured indices showed any significant link with risk for developing Alzheimer’s disease after adjustment for demographic, health-related, genetic, medication use, or behavioral factors. No significant differences by race were observed regarding how cortisol related to cognitive outcomes.
The authors note several limitations including the observational design; possible residual confounding; reliance on a single-day sampling protocol; lack of perceived stress assessment; use of older diagnostic criteria for Alzheimer’s disease; absence of adjustments for multiple comparisons; and limited generalizability beyond urban Black and White older adults in Chicago. The findings suggest salivary cortisol may help characterize subtle changes associated with early neurocognitive aging, but its predictive value for incident Alzheimer’s disease remains uncertain.
