Menopause is often associated with hot flashes, anxiety, brain fog and sleep problems, suggesting that the transition affects not only the body but also the brain. Now, researchers at UC San Francisco have identified biological changes that may help explain this connection — and potentially offer clues about women’s brain health decades later.

In a study published in Nature Medicine, researchers found that levels of 16 blood molecules linked to brain ageing changed during the menopause transition. In older women, higher levels of these same molecules were associated with poorer memory and thinking skills and a greater risk of Alzheimer’s disease. The researchers stress that menopause itself does not appear to cause dementia directly, but these biological changes could eventually help predict future risk.

Women account for about two-thirds of people with Alzheimer’s disease, a difference that cannot be explained entirely by women’s longer average lifespan. Because the earliest brain changes associated with Alzheimer’s can begin decades before symptoms appear, researchers are increasingly interested in midlife — particularly the years surrounding menopause — as an important period for understanding later brain health.

To examine this period more closely, researchers studied 80 women in their 40s and 50s. Rather than simply classifying them as pre- or postmenopausal, they used symptoms and hormone levels to determine where each woman was in the menopause transition, which can begin years before the final menstrual period and continue afterwards.

Using a blood test measuring more than 100 molecules related to brain health, the researchers identified 16 that changed across menopause. These changes were more strongly associated with hormone levels than with chronological age. Inflammatory molecules tended to increase as estradiol declined, while molecules associated with Alzheimer’s biology increased as follicle-stimulating hormone levels rose. Similar patterns were found in data from more than 2,800 women in the UK Biobank.

The researchers then examined nearly 12,000 women in their 60s and early 70s from four previous studies. Women with the highest levels of these molecules had poorer memory and a 15% higher risk of developing Alzheimer’s disease as they aged. Women who experienced night sweats during menopause also tended to show greater increases in inflammatory molecules, and elevated levels remained detectable years later among some women who recalled having hot flashes.

However, the findings show associations rather than cause and effect. Researchers do not yet know whether menopause directly triggers brain changes that increase dementia risk. Interestingly, a small group of middle-aged men showed much of the same molecular pattern seen in postmenopausal women, raising the possibility that menopause may accelerate biological changes that occur more gradually in men.

The long-term goal is to develop a blood test that could provide an early warning of dementia risk, similar to the way cholesterol testing helps assess cardiovascular risk. Researchers are now launching the Longitudinal Menopause Project, which will follow women through menopause using blood tests, brain MRI scans, cognitive testing, wearables and smartphone monitoring. The hope is that identifying risk during midlife could eventually create opportunities to strengthen brain resilience long before dementia symptoms appear.

More information: Madeline Wood Alexander et al, Blood proteomics of menopause map to brain aging and dementia risk, Nature Medicine. DOI: 10.1038/s41591-026-04648-4

Journal information: Nature Medicine Provided by University of California – San Francisco