Scientific Reports (Mar 2024)

Sex-specific associations of serum cortisol with brain biomarkers of Alzheimer’s risk

  • Lisa Mosconi,
  • Schantel Williams,
  • Caroline Carlton,
  • Camila Zarate,
  • Camila Boneu,
  • Francesca Fauci,
  • Trisha Ajila,
  • Matilde Nerattini,
  • Steven Jett,
  • Caroline Andy,
  • Michael Battista,
  • Silky Pahlajani,
  • Joseph Osborne,
  • Roberta Diaz Brinton,
  • Jonathan P. Dyke

DOI
https://doi.org/10.1038/s41598-024-56071-9
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 13

Abstract

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Abstract Emerging evidence implicates chronic psychological stress as a risk factor for Alzheimer’s disease (AD). Herein, we examined the relationships between serum cortisol and multimodality brain AD biomarkers in 277 cognitively normal midlife individuals at risk for AD. Overall, higher cortisol was associated with lower total brain volume, lower glucose metabolism (CMRglc) in frontal cortex, and higher β-amyloid (Aβ) load in AD-vulnerable regions; and marginally associated with phosphocreatine to ATP ratios (PCr/ATP) in precuneus and parietal regions. Sex-specific modification effects were noted: in women, cortisol exhibited stronger associations with Aβ load and frontal CMRglc, the latter being more pronounced postmenopause. In men, cortisol exhibited stronger associations with gray matter volume and PCr/ATP measures. Higher cortisol was associated with poorer delayed memory in men but not in women. Results were adjusted for age, Apolipoprotein E (APOE) epsilon 4 status, midlife health factors, and hormone therapy use. These results suggest sex-specific neurophysiological responses to stress, and support a role for stress reduction in AD prevention.