Women are more likely than men to develop dementia, and not just because they tend to live longer. One reason may be menopause, the time in midlife when sex hormones drop and menstruation stops—and which some researchers are coming to see as a stress test for the brain.

Menopause “affects brain health, for sure,” says neurologist Riley Bove of the University of California (UC) San Francisco, who studies its impacts on multiple sclerosis and other neurological disorders. She and others want to protect the brain during and after this transition—but that means identifying just how menopause puts the brain at risk.

A study published last week in Nature Medicine has found clues in the blood of women in their 40s and 50s: proteins related to brain function, inflammation, and neurodegenerative disease that are elevated during menopause. Other ongoing studies are following groups of women over time—including during the lesser studied perimenopausal stage, from just before menstruation ends to 1 year after—to reveal processes leading to short- and long-term cognitive problems.

Menopause is generally thought of in relation to the ovaries, which stop producing estrogen and progesterone. But the brain, which also produces hormones and is full of hormone receptors, plays key roles in the transition. Levels of follicle-stimulating hormone (FSH), produced in the pituitary gland, rise as sex hormones fall. Specialized neurons in the hypothalamus, deprived of estrogen, cause blood vessels to dilate, resulting in so-called vasomotor symptoms including night sweats and hot flashes.

And the brain itself is vulnerable. Severe or frequent vasomotor symptoms are associated with white matter hyperintensities, a type of brain lesion linked to dementia and stroke, as well as markers of Alzheimer’s disease pathology. Mood and sleep disturbances worsen in tandem with vasomotor symptoms, as do memory and other cognitive issues often collectively described as “brain fog.” Epidemiological and autopsy studies have shown that earlier menopause, whether spontaneous or caused by surgery to remove the ovaries, is associated with higher risk of Alzheimer’s.

But because menopause is an inevitable product of aging, the main risk factor for dementia, it’s hard to clearly separate its effects from those of age, Bove says. Few brain banks or long-running studies have detailed data on menopause, least of all from people actively going through it.

As one way to probe the biology behind the elevated risks, researchers led by neuropsychologist Kaitlin Casaletto of UC San Francisco studied a cohort of 80 healthy women in the premenopausal, perimenopausal, or early postmenopausal phase who were not taking hormones to treat menopause symptoms. They identified a molecular “signature” consisting of 16 brain-related proteins that were elevated in the blood of postmenopausal women compared with premenopausal women.

Two of these proteins are associated with Alzheimer’s, and several more play roles in neuronal or synaptic health. Inflammatory signaling proteins called cytokines were especially high among women who reported night sweats. Madeline Wood Alexander, a Ph.D. candidate at the University of Toronto and the study’s first author, says the findings suggest a “persistent inflammatory response could turn on during the menopause transition,” creating trouble for the brain.