Circulating stress hormones, brain health, and cognition in healthy older adults: Cross-sectional findings and sex differences in AGE-WELL

Abstract

Background

Increased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined the cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups.

Methods

Baseline data from 132 cognitively unimpaired non-depressed participants (age=74.0±4.0 years, women: n=80) in the Age-Well trial (NCT02977819) were included. Stress hormone levels were measured in overnight fasting blood serum (cortisol, dehydroepiandrosterone sulfate (DHEAS)) and blood plasma (epinephrine, norepinephrine) samples. AD-sensitive measures of brain health, including glucose metabolism (n=89), cerebral perfusion, gray matter volume, and amyloid deposition in a priori regions of interest, and cognitive markers were evaluated. Models were adjusted for age, sex, education, trait anxiety, and depressive symptoms.

Results

Higher epinephrine was associated (pFDR<0.05) with lower glucose metabolism in the anterior cingulate cortex (ACC, β=-0.26, p=.008), posterior cingulate cortex (PCC, β=-0.32, p=.006) and precuneus (β=-0.27, p=.021) and lower perfusion in the PCC (β=-0.23, p=.013). Interactions between stress hormones and sex showed (pFDR<0.05) that in women only, higher epinephrine was associated with larger ACC volume (interaction: β=0.32, p=.016), whereas in men only, higher cortisol was associated with lower episodic memory performance (interaction: β=0.98, p=.012).

Conclusions

The present study demonstrates the involvement of circulating stress hormones, particularly epinephrine and cortisol, in higher resilience or vulnerability of brain health and cognition indicators susceptible to AD in older adults. The identification of sex-specific patterns in these associations may inform the development of more effective and tailored interventions.