Menopause is often thought of as the end of the reproductive years and a stretch of hot flashes and poor sleep. A new study suggests it also leaves a mark in the blood that may be connected to how a woman’s brain ages decades later. Researchers at UC San Francisco, UC Santa Barbara and partner institutions reported that 16 molecules tied to brain aging and dementia risk rise across the menopause transition, in findings published in the journal Nature Medicine1.
“Menopause is not an isolated reproductive event,” said Emily Jacobs, a professor of psychological and brain sciences at UC Santa Barbara1. The researchers stress that the proteins do not directly lead to dementia, and that the study shows links, not causes1.
What the researchers found
The team used proteomics, a technology that measures thousands of proteins in a blood sample at once1. They studied women at three stages: before menopause, during the transition (perimenopause) and after menopause. The women came from the Healthy Aging Study run by Jacobs’s lab, which looks at brain and thinking skills in women and men in midlife1.
They found a set of proteins that changed across the transition. These included proteins involved in inflammation and in nerve cells, as well as molecules associated with Alzheimer’s disease1. In all, levels of 16 molecules linked to brain aging and dementia risk went up1.
One detail matters for how the results are read. The protein shifts lined up more closely with a woman’s menopause stage than with her exact age. The researchers take this as a sign that menopause itself, not just getting older, drove the changes1.
How the finding was checked
The team did not rely on one group of women. They first confirmed the protein pattern in more than 2,800 women from the UK Biobank, a large British health database. That data also tied menopause to molecular signs of faster aging across several organ systems, not only the brain1.
Next, they asked whether the pattern related to brain health later in life. They looked at four separate groups of older women, nearly 12,000 in total1. Women with higher levels of the “risk” proteins were more likely to have poorer results on thinking and memory measures1. In the largest group, the protein signature was linked to a modestly greater risk of developing Alzheimer’s dementia over the following 16 years1.
A paper by the same lead authors, titled “Plasma proteomics link menopause timing to brain aging and dementia risk,” was posted on medRxiv in April 20262. medRxiv is a site where researchers share papers before peer review, the checking process journals use. The university’s announcement describes the work as now published in Nature Medicine1.
What it does not show yet
This is an observational study. It tracks what tends to go together in large groups of people. It cannot show that the proteins, or menopause, cause later memory problems.
The researchers say so directly. “The findings do not mean that menopause causes Alzheimer’s disease,” said Kaitlin Casaletto, the study’s senior author1. She noted that most women do not develop Alzheimer’s, and that the clinical meaning of individual Alzheimer’s-related protein changes seen in midlife remains uncertain1.
Other limits are worth keeping in mind:
- The link to Alzheimer’s dementia was described as “modestly greater” risk, and it was reported in the largest group, not in all four1.
- The main comparison set women at different menopause stages side by side, rather than following the same women through the change. The authors say studies that follow the same women over time are essential to see how hormones, proteins, symptoms and brain health unfold together1.
- There is no test or treatment based on these proteins yet. A blood test is a goal, not a product1.
Who did the work and who paid for it
The study was led by Madeline Wood Alexander at Sunnybrook Research Institute in Canada and by Rowan Saloner and Kaitlin Casaletto at UCSF, with collaborators at UC Santa Barbara, Stanford University, the University of Toronto and other institutions1. The author list on the April preprint also includes researchers from the National Institute on Aging, the Icahn School of Medicine at Mount Sinai, the Fred Hutchinson Cancer Center and the University of Washington, among others2.
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 Trust1. Both Jacobs and Casaletto list an affiliation with the Ann S. Bowers Women’s Brain Health Initiative2. The sources do not mention any company funding or commercial ties to a test.
How it fits the field
Interest in menopause and the brain has grown quickly. Estrogen, the hormone that drops at menopause, acts in brain regions tied to memory and planning, including the hippocampus and prefrontal cortex3. Women make up nearly two-thirds of Alzheimer’s cases, a pattern that longer life expectancy explains only in part, according to a summary from the Ikigai Health Institute3.
Many researchers now frame the question differently than before. Rather than asking whether menopause directly causes Alzheimer’s, for which there is little evidence, they ask whether it makes the brain more vulnerable, or less resilient, to other processes that build up over decades3. Brain scan studies have seen changes in how some women’s brains use sugar for energy during perimenopause, changes that often seem to settle after menopause3. Observational studies also suggest that women whose ovaries are surgically removed before natural menopause may face a higher long-term risk of memory decline and dementia, though the reasons are still unclear3.
The new study adds a blood-based angle to that picture. “Now we can begin to see a molecular fingerprint of that transition in the blood and ask how it relates to brain health decades later,” Jacobs said1. “Women spend roughly one third of their lives after the menopause transition, yet we know remarkably little about the biology connecting menopause to later-life brain health,” she added1.
Biohack has also covered other recent menopause research, including a large study on modern hormone therapy and heart attacks and strokes.
What to watch next
The team’s stated goal is a blood test that could serve as an early warning of dementia risk, the way cholesterol tests are used to gauge heart disease risk1. Such a test, if it were ever developed and validated, could help doctors spot people in midlife who might benefit from early steps to protect the brain1.
“Midlife is a critical window for both men and women where we can really set up the brain to be more resilient or more vulnerable to dementia in later life,” Casaletto said. “For women, menopause may be this especially powerful time to intervene.”1
The next step is the Longitudinal Menopause Project, which UC Santa Barbara’s team is launching with scientists around the country. It will follow the same women across the menopause transition, and the group is actively recruiting researchers1. Key questions for that work:
- Do the same 16 proteins rise within individual women as they move through menopause?
- Do changes in the proteins track with symptoms such as brain fog and sleep problems?
- Can any intervention in midlife change the protein pattern, and would that matter for the brain later?
Until those answers come in, the finding is best read as a map of biological changes that line up with menopause, not as a forecast for any one woman.
