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

Publication Type	Academic Article
Authors	Mosconi L, Williams S, Carlton C, Zarate C, Boneu C, Fauci F, Ajila T, Nerattini M, Jett S, Andy C, Battista M, Pahlajani S, Osborne J, Brinton R, Dyke J
Journal	Sci Rep
Volume	14
Issue	1
Pagination	5519
Date Published	03/06/2024
ISSN	2045-2322
Keywords	Hydrocortisone, Alzheimer Disease
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.
DOI	10.1038/s41598-024-56071-9
PubMed ID	38448497
PubMed Central ID	PMC10918173