A LARGE Chicago-based cohort study has revealed that patterns of diurnal salivary cortisol are associated with cognitive decline in older adults, with distinct racial differences in cortisol rhythms that did not alter the strength of the cortisol-cognition association.
Salivary Cortisol as a Marker of Cognitive Aging
Alterations in hypothalamic-pituitary-adrenal axis activity have been implicated in cognitive aging, yet large, racially diverse studies using physiologically active salivary cortisol have remained limited. Whether diurnal salivary cortisol indices are associated with cognitive outcomes, including incident Alzheimer disease, and whether these associations differ by race, has remained an important gap in the literature.
Chicago Health and Aging Project Cohort Design
Researchers conducted a prospective cohort study from 2000 to 2011, with 11 years of follow-up, as part of the Chicago Health and Aging Project, a community-based study of older adults. Participants provided salivary cortisol samples across the day (waking, afternoon, and bedtime) and completed cognitive assessments.
Cortisol Patterns Linked to Cognitive Decline
Among 3,895 participants (mean age 76.7 years; 64.4% women; 64.3% Black and 35.7% White), all cortisol indices were cross-sectionally associated with cognitive performance. Longitudinally, medium to high intraday variability was associated with slower decline versus the lowest quintile (Q3: β=0.02, 95% CI 0.001 to 0.04, p=0.04; Q4: β=0.03, 95% CI 0.01 to 0.04, p=0.003), whereas the highest cumulative exposure was associated with faster decline (mean cortisol Q5: β=−0.02, 95% CI −0.04 to −0.004, p=0.02; AUCg Q5: β=−0.02, 95% CI −0.03 to 0.00, p=0.046). Diurnal change indices were not associated with decline or incident Alzheimer disease. Black participants showed lower cumulative cortisol exposure, flatter diurnal slopes, and lower intraday variability, reflecting a blunted diurnal rhythm, although associations with cognitive decline were similar across racial groups.
Implications for Early Detection and Health Equity
These findings have supported salivary cortisol as a potential early biomarker of neurocognitive ageing, although it was not associated with short-term Alzheimer disease risk in this cohort. As this was an observational study, causality cannot be established. The authors have suggested that racial differences in cortisol patterning may reflect differential biological embedding of stress consistent with structural inequities.
Reference
Ng TKS et al. Salivary cortisol and cognitive decline and Alzheimer disease in older adults. JAMA Netw Open. 2026;9(7):e2622955.
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