Scientists at UC Santa Barbara, UC San Francisco, and international partners have identified molecular changes in the blood that occur during menopause and may influence brain health decades later. The study, published in Nature Medicine, examined how the body responds to this transition, which involves hormonal shifts and symptoms like hot flashes and brain fog.
A molecular fingerprint emerges
The research focused on 16 molecules linked to brain aging and dementia risk. Researchers used advanced proteomic technologies to analyze thousands of proteins in cohorts of pre-, peri-, and postmenopausal women. They found that protein levels shifted more closely to a woman’s menopause stage than her chronological age.
These results were confirmed in a database of over 2,800 women from the UK Biobank. The data showed that menopause is tied to molecular signatures of accelerated aging across multiple organ systems. The authors note that longitudinal studies following the same women across the transition will be essential to determine how changes in hormones, proteins, and brain health unfold together over time.
Connecting blood markers to cognitive outcomes
By analyzing data from four independent cohorts totaling nearly 12,000 older women, the team investigated this biological transition’s link to brain health. They found that women with higher levels of these “risk” proteins were more likely to show poorer cognitive outcomes. In the largest cohort, this signature was associated with a modestly greater risk of developing Alzheimer’s dementia over the following 16 years.
The study highlights the importance of menopause as a window to study brain aging. The authors note that women spend roughly one third of their lives after the menopause transition, yet little is known about the biology connecting the two. The goal is to develop a blood test that can act as an early-warning sign of dementia risk, similar to how cholesterol tests gauge heart disease risk.
Next steps in research
The team, led by Madeline Wood Alexander at Sunnybrook Research Institute in Canada and Rowan Saloner and Kaitlin Casaletto at UCSF, is now launching the Longitudinal Menopause Project. This initiative will follow women across the menopause transition to better understand the progression of symptoms and biological changes.
Collaborators from Stanford University, the University of Toronto, and other institutions are working on the project. The work was supported in part by the Ann S. Bowers Women’s Brain Health Initiative, Wellcome Leap, the National Institutes of Health, and the Noyce Trust.
