JAMA network open · 2026
Salivary Cortisol and Cognitive Decline and Alzheimer Disease in Older Adults.
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Ng Ted K S, Beck Todd, Sudhini Yashwanth, Wilson Robert S, Evans Denis A, Rajan Kumar B
Аннотация
IMPORTANCE: Alterations in hypothalamic-pituitary-adrenal axis activity have been implicated in cognitive aging, yet large, racially diverse studies using physiologically active salivary cortisol studies are limited.
OBJECTIVE: To determine whether diurnal salivary cortisol indices are associated with cognitive outcomes, including incident Alzheimer disease (AD), and whether distributions and associations differ by race.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted 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 in urban Chicago. Participants provided salivary cortisol samples across a day (waking, afternoon, and bedtime) and completed cognitive assessments. Analyses were conducted from June to October 2025.
EXPOSURES: Five salivary cortisol indices capturing intraday variability (coefficient of variation [CV]), cumulative exposure (mean cortisol and area under the curve with respect to ground [AUCg]), and diurnal change (diurnal slope and AUC with respect to increase [AUCi]).
MAIN OUTCOMES AND MEASURES: Outcomes of interest were global cognition, cognitive decline, and incident AD, adjusted for demographic, health, and behavioral factors.
RESULTS: Among 3895 participants (mean [SD] age, 76.7 [6.8] years; 2509 [64.4%] women; 2503 Black participants [64.3%] and 1392 White participants [35.7%]), all cortisol indices were cross-sectionally associated with cognitive performance. Longitudinally, compared with the first quintile (Q1), medium to high cortisol intraday variability (CV) was associated with slower decline (Q3: β = 0.02 [95% CI, 0.001 to 0.04]; P = .04; Q4: β = 0.03 [95% CI, 0.01 to 0.04]; P = .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 = .02; AUCg Q5: β = -0.02 [95% CI, -0.03 to 0.00]; P = .046). Diurnal change indices (slope, AUCi) were not associated with decline or incident AD. Black participants exhibited lower cortisol exposure but flatter slopes and lower intraday variability, reflecting a blunted diurnal rhythm; associations with decline were similar across races.
CONCLUSIONS AND RELEVANCE: In this cohort study of Black and White older adults, altered diurnal cortisol patterning was associated with faster cognitive decline but not short-term AD risk. These findings support salivary cortisol as a potential early biomarker of neurocognitive aging. Racial differences in cortisol patterning suggest differential biological embedding of stress, consistent with structural inequities.
OBJECTIVE: To determine whether diurnal salivary cortisol indices are associated with cognitive outcomes, including incident Alzheimer disease (AD), and whether distributions and associations differ by race.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted 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 in urban Chicago. Participants provided salivary cortisol samples across a day (waking, afternoon, and bedtime) and completed cognitive assessments. Analyses were conducted from June to October 2025.
EXPOSURES: Five salivary cortisol indices capturing intraday variability (coefficient of variation [CV]), cumulative exposure (mean cortisol and area under the curve with respect to ground [AUCg]), and diurnal change (diurnal slope and AUC with respect to increase [AUCi]).
MAIN OUTCOMES AND MEASURES: Outcomes of interest were global cognition, cognitive decline, and incident AD, adjusted for demographic, health, and behavioral factors.
RESULTS: Among 3895 participants (mean [SD] age, 76.7 [6.8] years; 2509 [64.4%] women; 2503 Black participants [64.3%] and 1392 White participants [35.7%]), all cortisol indices were cross-sectionally associated with cognitive performance. Longitudinally, compared with the first quintile (Q1), medium to high cortisol intraday variability (CV) was associated with slower decline (Q3: β = 0.02 [95% CI, 0.001 to 0.04]; P = .04; Q4: β = 0.03 [95% CI, 0.01 to 0.04]; P = .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 = .02; AUCg Q5: β = -0.02 [95% CI, -0.03 to 0.00]; P = .046). Diurnal change indices (slope, AUCi) were not associated with decline or incident AD. Black participants exhibited lower cortisol exposure but flatter slopes and lower intraday variability, reflecting a blunted diurnal rhythm; associations with decline were similar across races.
CONCLUSIONS AND RELEVANCE: In this cohort study of Black and White older adults, altered diurnal cortisol patterning was associated with faster cognitive decline but not short-term AD risk. These findings support salivary cortisol as a potential early biomarker of neurocognitive aging. Racial differences in cortisol patterning suggest differential biological embedding of stress, consistent with structural inequities.