Blunted Diurnal Cortisol Slope as a Risk Marker for 9-Year Executive Function Decline: Amplification by Daily Stress...

Cortisol dysregulation, reflective of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, has been linked to executive functioning (EF) decline. However, substantial effect-size heterogeneity across studies highlights the potential role of psychosocial moderators. We investigated whether the severity of perceived daily stressors and chronic worry moderated the relationships between baseline cortisol dysregulation and 9-year EF.

Community adults (N = 1,617) completed four-day, four-times-daily salivary cortisol sampling and an eight-day interview-driven daily diary at baseline. Three cortisol metrics were computed: area under the curve (AUC), cortisol awakening response (CAR), and diurnal cortisol slope (DCS). Linear mixed models determined whether daily stressor or chronic worry severity moderated associations between baseline cortisol metrics and 9-year EF, adjusting for baseline EF.

Daily stressor severity significantly moderated the relationship between DCS-but not AUC or CAR-and 9-year EF (Cohen's d = 0.113). Flatter DCS was associated with poorer EF across all stressor severity levels, although the observed numerical attenuation at higher severity was not statistically confirmed. Chronic worry severity was significantly associated with lower 9-year EF across all cortisol metrics and significantly moderated the CAR-to-EF relationship (d = -0.176). Exploratory analyses suggested that a flatter DCS was associated with worse EF at higher worry severity, but this interaction was not significant.

These outcomes broadly align with moderation, not mediation, suggesting that psychosocial stress and worry can amplify, rather than yield, cortisol-linked relationships with EF. Pending replication, HPA-axis circadian modulation and chronic worry severity can indicate viable targets for prevention research.