Summary: A new study finds that elevated cortisol levels in midlife are linked to increased brain amyloid deposition—a key marker of Alzheimer’s disease—specifically in post-menopausal women. Researchers tracked 305 cognitively healthy individuals over 15 years and discovered that high cortisol predicted amyloid buildup later in life, but only among women who had gone through menopause.
The findings suggest that hormonal changes may amplify cortisol’s harmful effects on brain health. No similar relationship was found in men or with tau protein, another Alzheimer’s marker.
Key Facts:
- Sex-Specific Risk: High midlife cortisol predicted Alzheimer’s risk only in post-menopausal women.
- Amyloid Link: Cortisol levels were associated with increased amyloid buildup, not tau.
- Prevention Potential: Findings suggest early stress reduction and hormone-based strategies could lower Alzheimer’s risk.
Source: UT San Antonio
Can stress lead to Alzheimer’s disease? It can in women who are post-menopausal, a study led by The University of Texas Health Science Center at San Antoino (UT Health San Antonio) shows.
Analyzing data from 305 cognitively unimpaired participants in the Framingham Heart Study, a long-term and ongoing community-based cohort study of residents in Framingham, Massachusetts, the scientists discovered that high levels of the stress hormone cortisol in midlife are linked to increased amyloid deposition in post-menopausal persons later.
Amyloids are proteins that have folded incorrectly, preventing biologic function, forming deposits in tissues and organs, and implicated in Alzheimer’s disease.
By comparing midlife cortisol levels at the beginning of a 15-year period with disease indicators at the end, the researchers were able to determine that those levels could serve as an Alzheimer’s disease biomarker, with particular attention to gender differences and menopausal status.
No significant associations were observed in males or with tau burden, referring to the tau protein that contributes to neuronal dysfunction and death.
“The results highlight the importance of identifying early risk factors when biomarkers are detectable but cognitive impairment is absent,” said Arash Salardini, MD, associate professor of cognitive and behavioral neurology with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio.
Salardini is first author of the study titled, “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,” published April 24 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Other authors also are with UT Health San Antonio, as well as the University of Texas School of Public Health San Antonio; Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health; Boston University; Gonzaba Medical Group, San Antonio; University of Galway, Ireland; Cedars-Sinai Medical Center; Massachusetts General Hospital/Harvard Medical School; New York University Grossman School of Medicine; Brigham and Women’s Hospital; Yale University; and the University of California at Davis.
“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 Sudha Seshadri, founding director of the Biggs Institute and senior author of the study.
Targeting risk factors early
The study notes that “sporadic” Alzheimer’s disease is the leading cause of cognitive decline in older adults. That features a prolonged asymptomatic phase of amyloid beta accumulation, the main component of amyloid plaques, eventually triggering progressive cognitive decline.
Recognizing that these biological changes are already well established by the time symptoms emerge, effective early interventions must target Alzheimer’s disease risk factors during the preclinical stages.
However, despite significant advancements in understanding how the disease affects the body’s normal biological processes, more than half of the overall risk has remained unexplained, underscoring the critical need to identify additional risk factors that can be targeted during the preclinical stage.
One promising line of investigation centers on cortisol, a steroid hormone essential for cellular homeostasis, or balance, and the stress response.
Genetic studies had identified mutations in glucocorticoid, or steroid hormones that have anti-inflammatory and immunosuppressive effects, signaling pathways that increase susceptibility to Alzheimer’s disease.
Also, several cross-sectional and longitudinal studies had reported that higher blood cortisol levels are linked to an increased likelihood of developing the disease.
To address gaps and inconsistencies across those studies, the researchers led by UT Health San Antonio conducted a longitudinal analysis using data from the third-generation cohort of the Framingham Heart Study, which dates to 1948 and now is directed by the National Heart, Lung, and Blood Institute of the National Institutes of Health.
They assessed the relationship between serum cortisol levels in the 305 cognitively unimpaired, middle-aged individuals – 48.5% female, with a mean age of 39.6 years –and amyloid/tau burdens approximately 15 years later using positron emission tomography (PET) imaging. And they performed multivariable regression analyses adjusted for confounders.
All this allowed them to investigate cortisol’s impact at an earlier stage of Alzheimer’s disease pathogenesis, where interventions might be most effective.
Given the neuroprotective effects of estrogen and testosterone, which mitigate cortisol’s deleterious impact on neural tissues, they also explored sex-specific differences, focusing particularly on post-menopausal risk.
They hypothesized that cortisol’s impact on Alzheimer’s pathology would be more pronounced in women, especially after menopause, consistent with some previous findings.
Indeed, they found that post-menopausal women with high midlife cortisol are at increased risk of Alzheimer’s disease, and that post-menopausal hormone changes may amplify cortisol’s effects on amyloid.
“Longitudinal follow-up of our cohort will be crucial to determine whether these early amyloid changes translate into clinical symptoms and to clarify the causal role of cortisol in Alzheimer’s disease development,” Salardini said.
About this Alzheimer’s disease research news
Author: Steven Lee
Source: UT San Antonio
Contact: Steven Lee – UT San Antonio
Image: The image is credited to Neuroscience News
Original Research: Open access.
“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” by Arash Salardini et al. Alzheimer’s & Dementia
Abstract
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
INTRODUCTION
This study investigates whether midlife cortisol levels predict Alzheimer’s disease (AD) biomarker burden 15 years later, with particular attention to sex differences and menopausal status.
METHODS
We analyzed data from 305 cognitively unimpaired Framingham Heart Study participants (48.5% female; mean age: 39.6 ± 8.1 years). Serum cortisol was categorized into tertiles, with amyloid ([11C]PiB) and tau ([18F]Flortaucipir) positron emission tomography (PET) imaging conducted 15 years later. We performed multivariable regression analyses adjusted for confounders including, apolipoprotein E4 (APOE4) status.
RESULTS
Elevated midlife cortisol correlated with increased amyloid deposition, specifically in post-menopausal women, predominantly in posterior cingulate, precuneus, and frontal-lateral regions (p < 0.05). No significant associations were observed with tau burden or in males.
DISCUSSION
These findings reveal post-menopausal women with high midlife cortisol are at increased risk of AD. Results highlight the importance of identifying early risk factors when biomarkers are detectable but cognitive impairment is absent.
