Alzheimer’s in Women

Having more hot flashes, especially night sweats, during the transition to menopause may be associated with a greater risk of developing Alzheimer’s disease later in life, according to a new study led by a University of Pittsburgh scientist.

Psychiatry professor Rebecca Thurston, PhD, Pittsburgh Foundation Chair in Women’s Health and Dementia and director of Pitt’s Women’s Biobehavioral Health Laboratory, recently presented the findings at the 2023 annual meeting of the Menopause Society in Philadelphia, building on earlier research that has shown relationships between hot flashes, natural hormone fluctuations, cardiovascular changes, and brain health.

“All women will go through the menopause transition,” Thurston said. “Not only do women go through dramatic hormonal changes, but most women also experience menopausal symptoms including hot flashes, night sweats, and sleep problems and, for many women, brain fog. So, the menopause transition is a very important window into women’s brain health, as well as their cardiovascular health.”

The research team, which was co-led by Thurston’s longtime collaborator Pauline Maki, PhD, of the University of Illinois, tracked 248 women between the ages of 45 and 57 during their three-year, NIH-funded MS Brain study. The participants wore devices that objectively measured their “vasomotor symptoms,” or hot flashes and night sweats, as well as sleep. The team performed blood tests for Alzheimer’s-associated biomarkers, including the Aβ42/40 ratio; too-low values are an early indicator that the disease is developing even though symptoms such as forgetfulness and confusion haven’t yet appeared.

Women who experienced more objectively assessed night sweats, or hot flashes during sleep, had lower Aβ42/40 ratios, the researchers learned. The reasons for those links must be examined because they could point the way to new interventions to slow or prevent Alzheimer’s dementia, Thurston said.

Before joining the Pitt faculty in 2005, she was familiar with the contributions made by Pitt researchers Lewis Kuller and Karen Matthews to the Women’s Health Initiative (WHI) and the Healthy Women Study, which examined hormone replacement therapy during menopause and cardiovascular disease risk and the natural history of the menopause transition. Thurston is also a principal investigator of the Study of Women’s Health Across the Nation (SWAN), a large prospective study that has generated significant discoveries about the menopause transition.

Then, “about eight years ago, I teamed up with a neuroscience colleague. I was doing work on menopausal symptoms and cardiovascular health, and she was doing work around menopausal symptoms and cognition, and we wanted to marry these two things together,” Thurston said.

Their collaboration led to the Ms Brain Study, which produced novel findings about brain health in women. For example, Thurston’s team noted that women who had hot flashes, particularly during sleep, were more likely to have brain scans that show “white matter hyperintensities.”

“White matter hyperintensities are markers of small-blood vessel disease in the brain that show up basically as white spots on certain kinds of MRI images of the brain,” Thurston explained. “They grow over time and can appear in different areas of the brain. These white matter hyperintensities, particularly when there are many of them, are linked to future risk for stroke and dementia.”

She is continuing to explore the links between the menopause transition and brain health in the MsBrain 2 study, which is also funded by the NIH.

“Our research is unique because we are studying women at midlife, while a lot of the research in Alzheimer’s among people 65 and older,” Thurston said. “There is great interest in trying to understand midlife determinants of Alzheimer’s risk, because we believe the disease mechanisms are really starting to get laid down many years before memory and other cognitive symptoms start.”

For more information about the MsBrain study, email msbrain@pitt.edu.