Most people who develop Alzheimer’s disease are women. In fact, women account for two-thirds of all Alzheimer’s patients—a higher proportion than can be explained merely by their longer lifespans. So what causes the discrepancy?
It’s possible that menopause, which men very notably do not experience, could be involved.
During menopause, hormone levels change, with estrogen tapering off as follicle-stimulating hormone rises. These hormonal changes lead to vasomotor symptoms like hot flashes, night sweats, and more. But many women also experience cognitive effects, like difficulty finding the right word or focusing their attention. Additionally, brain regions susceptible to Alzheimer’s express receptors for hormones that shift during The Change. Now, a new study published in Nature Medicine is uncovering the role this inflection point may play in developing Alzheimer’s disease by looking at blood biomarkers.
Read more: “The Evolutionary Mystery of Menopause”
“We don’t think that menopause is directly causing dementia,” study author Kaitlin Casaletto of the University of California, Santa Barbara explained in a statement. “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.”
Casaletto and a team of fellow neuroscientists recruited 80 women in their 40s and 50s and determined where they were in their menopausal transition with a measure that combines symptoms and hormone levels. They then tested the women’s blood for hundreds of biomarkers and identified 16 whose levels were associated with menopausal changes. Importantly, these molecules were more closely linked to shifting hormone levels than the women’s ages, a strong suggestion the changes were related to menopause.
As estrogen levels fell, the researchers discovered proteins involved in inflammation pathways rose. This coincides with a general increase in postmenopausal inflammation other researchers have found that could set the stage for later neurodegenerative diseases. As follicle-stimulating hormone levels surged, levels of other proteins involved in synaptic function also climbed. These proteins are biomarkers for Alzheimer’s disease as well.
Of course, 80 women isn’t the largest sample size, so the team analyzed health data from more than 2,800 women enrolled in the United Kingdom’s BioBank study to confirm their findings. They then widened the scope of their investigation, looking at data from over 12,000 women in their 60s and 70s involved in four other studies. They found that women with the highest levels of these proteins had both poorer memories and a 15 percent higher risk of developing Alzheimer’s disease later on.
The team uncovered links between vasomotor symptoms and these biomarkers as well. Women who reported night sweats during menopause also showed a bigger increase in inflammatory proteins. Additionally, older women who remembered experiencing hot flashes had higher levels of these proteins much later in life, which suggests a lingering effect.
It’s not all bad news, though. According to the team, these findings could pave the way for future blood tests that can act as an early warning system for women who are most at-risk. “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,” said Casaletto. “For women, menopause may be this especially powerful time to intervene.”
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