Stress Hormone Predicts Alzheimer’s Risk After Menopause
Higher midlife cortisol levels predict increased brain amyloid deposits in post-menopausal women.
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A study led by the University of Texas Health Science Center at San Antonio (UT Health San Antonio) found that elevated cortisol levels in midlife are associated with increased amyloid protein deposits in the brains of post-menopausal women. This suggests that stress may contribute to Alzheimer’s disease risk in this group.
Cortisol
A steroid hormone released in response to stress that helps regulate bodily functions but can damage neurons if elevated chronically.Amyloid
Proteins that fold incorrectly and accumulate in brain tissue, forming plaques that disrupt neuron communication in Alzheimer’s disease.Researchers analyzed data from 305 cognitively unimpaired participants in the Framingham Heart Study, a long-term community-based study in Massachusetts. They compared midlife serum cortisol levels with brain imaging of amyloid and tau proteins approximately 15 years later. High cortisol predicted increased amyloid accumulation specifically in post-menopausal individuals.
“The results highlight the importance of identifying early risk factors when biomarkers are detectable but cognitive impairment is absent,” said Dr. Arash Salardini.
Amyloid protein buildup as an early Alzheimer’s disease indicator
Amyloids are misfolded proteins that form deposits in the brain, disrupting normal function and playing a key role in Alzheimer’s disease. No significant associations were found between cortisol and tau protein, which is involved in neuron damage. The findings highlight amyloid as an early biomarker for Alzheimer’s risk linked to stress hormones.
Tau protein
A protein that stabilizes neurons but forms toxic tangles inside nerve cells in Alzheimer’s, contributing to cell death.Sex and hormonal status influence cortisol’s effect on brain health
The study focused on sex differences and menopausal status due to estrogen’s and testosterone’s neuroprotective effects, which may reduce cortisol’s harmful impact on neurons. Post-menopausal hormone changes appear to amplify cortisol’s role in amyloid deposition, increasing Alzheimer’s risk among women after menopause.
“Our work shows that considering sex and hormonal status in understanding Alzheimer’s disease pathogenesis is important, and suggests that stress reduction and hormonal interventions may hold promise for Alzheimer’s prevention, especially in at-risk women,” said Dr. Sudha Seshadri.
Alzheimer’s disease develops over years, with amyloid beta accumulation occurring long before cognitive symptoms. Identifying early risk factors such as elevated cortisol during midlife could improve prevention efforts, especially for women vulnerable due to hormonal changes.
Further follow-up of the Framingham cohort will determine whether early amyloid increases linked to cortisol lead to clinical Alzheimer’s symptoms and will help clarify the hormone’s causal role in disease progression.
Reference: Salardini A, Himali JJ, Abdullah MS, et al. Elevated serum cortisol associated with early‐detected increase of brain amyloid deposition in Alzheimer’s disease imaging biomarkers among menopausal women: The Framingham Heart Study. Alzheimer’s Dementia. 2025;21(4):e70179. doi: 10.1002/alz.70179
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