Menopause leaves fingerprint that may predict dementia risk – study

Blood markers that change during menopause are linked to poorer memory and higher Alzheimer’s disease risk in older women, a study found.

Researchers identified 16 molecules linked to brain health that shifted during the menopause transition. The changes were more closely associated with hormone levels than with age.

The findings were correlational, meaning they do not show that menopause directly causes brain changes or dementia. Researchers said further work is needed to understand what may drive the associations.

Kaitlin Casaletto, associate professor at the UCSF Fein Memory and Aging Center and co-senior author of the study, said: “We don’t think that menopause is directly causing dementia.

“But it’s possible that we may be able to predict a woman’s risk for dementia decades later by the levels of these molecules around menopause.”

The study, led by researchers at UC San Francisco, began with 80 women in their 40s and 50s. Symptoms and hormone levels were used to determine where each woman was in the menopause transition.

Menopause unfolds over several years as hormone levels change before and after menstrual periods permanently stop. Researchers measured more than 100 blood molecules linked to brain health and identified 16 that changed during this period.

Inflammation-related molecules tended to rise as levels of estradiol, a form of oestrogen, fell. Another group linked to Alzheimer’s disease biology rose as follicle-stimulating hormone levels increased.

Researchers replicated the findings using previously collected data from more than 2,800 women in the UK Biobank.

They then examined the same molecules in almost 12,000 women in their 60s and early 70s across four previous studies.

Older women with the highest levels of the molecules had worse memory and a 15 per cent higher risk of developing Alzheimer’s disease as they aged.

Women who reported night sweats tended to show greater increases in inflammatory molecules during menopause.

Among older women, those who recalled having hot flushes during menopause also had higher levels of the inflammatory markers years later.

A small sample of midlife men showed much of the same molecular pattern seen in postmenopausal women. Researchers suggested this could indicate that menopause is associated with a more rapid shift in biological ageing that occurs more gradually in men.

Madeline Wood Alexander, first author and a graduate student at the University of Toronto, said: “Menopause is a normal physiological process that every person who has ovaries who lives long enough will go through.

“We don’t want it to be viewed as a bad thing, but as an opportunity to better understand and maybe modify the biology of brain ageing in women.”

The researchers eventually hope to develop a blood test that could help identify dementia risk in midlife, but the current findings do not establish such a test for clinical use.

Casaletto and other researchers are also launching the Longitudinal Menopause Project, which will follow women through the menopause transition using twice-yearly blood tests, brain MRI scans, cognitive testing, wearables and smartphone-based monitoring.