(NewsNation) — Researchers have linked age, menopause, and hormone therapy as major risk factors associated with Alzheimer’s disease in women.

A new study published in JAMA Neurology found that early-age menopause could be a risk factor for Alzheimer’s disease dementia, but women who received hormone replacement therapy, or HRT, near the age of menopause onset didn’t show a higher risk.

Nearly two-thirds of people diagnosed with Alzheimer’s disease are women, according to the Alzheimer’s Association. Researchers said this is likely due to hormonal changes, which play a role in the development of this brain disorder.

The study broke down two likely contributing factors. Women lose sexual hormones such as estrogen when they enter menopause, either naturally through the body’s decreased production or by removal of the ovaries via surgery. Yet, exactly how the loss of those hormones and the impact of HRT affects dementia risk is unclear.

The study found that women who underwent early (age 40 to 45) or premature (pre-40) menopause or women who began HRT more than five years after menopause had higher levels of tau deposits in their brains.

Tau is a type of protein that in a person with Alzheimer’s disease can become tangled in neurons; they are a hallmark sign of the disease.

The study also found that women who started hormone therapy after five or six years of menopause, rather than at the start of menopause, had a great risk of developing Alzheimer’s disease.  

Rachel Buckley, Ph.D., a corresponding study author and ​an assistant professor in the Department of Neurology at Massachusetts General Hospital/Harvard Medical School, told Healthline that the “most goundbreaking” findings surround hormone therapy.

“Counterintuitively, we found that women with elevated amyloid and who reported taking hormone therapy also showed higher tau burden. One would have imagined taking hormone therapy might ameliorate the issues of lost estrogen because you are reintroducing estrogen into the body,” Buckley said.

After further investigation into the group of women who reported taking hormone therapy, researchers found that higher risk was only associated with those women who had a long gap between their menopause onset and hormone therapy initiation, Buckley told Healthline.

Other documented changes, like those in sleep patterns, mood and metabolism, occur during menopause and are also known risk factors for Alzheimer’s disease.

“Women live longer, and age is the single biggest risk factor for Alzheimer’s disease,” Dr. Carolyn Fredericks, a neurologist at Yale New Haven Health and an assistant professor at Yale School of Medicine, told Healthline. “In cultures where today’s older women had more access to factors that promote ‘cognitive reserve’ such as higher education, regular cardiovascular exercise, and intellectually challenging work, the gap between women’s risk and men’s risk is narrowing. In cultures that did not offer these opportunities to women as early, the gap is wider.”

Researchers are now studying sex hormones of people in midlife and tau burden in the brain.