A new study published Monday in the journal Neurology found an interesting connection between hormone replacement therapy, or HRT, and Alzheimer’s disease. The disease strikes women harder than men, says the Alzheimer’s Association, with two-thirds of the sufferers being female.

According to CNN, researchers found that women who go through early or premature menopause and begin taking HRT more than five years after menopause had higher levels of tau in their brains. Tau tangles, along with plaques made up of beta-amyloid proteins, are classic signs of Alzheimer’s disease.

“This is the first study showing a delayed use of hormone therapy seems to be associated with increased levels of Alzheimer's markers in the brain,” said Gillian Coughlan, a research fellow in neurology at Massachusetts General Hospital in Boston, who was the lead author of the study.

While it is not uncommon for older people to accumulate amyloid as they age, it is uncommon to see tau deposits. It takes both the tau deposits and the beta-amyloid plaque to develop Alzheimer’s disease.

“Usually if you’ve a combination of beta-amyloid and tau, then you would typically develop cognitive decline within a few years,” said Coughlan. “What we found is women who have early menopause or have a very late use of hormone therapy might be at higher risk, but only if they were already on the Alzheimer’s disease continuum, with elevated levels of amyloid. Women with very low levels and early menopause did not have such an association.”

But the study did find a “sweet spot” for the use of hormone therapy. Women who started HRT close to menopause did not have higher or lower levels of tau protein in the brain.

“This is good as it means we may still be able to use hormone therapy to treat severe menopausal symptoms,” Coughlan said.

For the new study, Coughlan, and a team of researchers from Massachusetts General Hospital analyzed brain scans of 193 women and 99 men with normal cognitive function to determine beta-amyloid and tau levels.

According to MedPage Today, the findings add to an increasing body of literature indicating that menopause — especially early or premature menopause — is one contributor to women’s greater lifelong risk of Alzheimer’s disease.

“This study also indicates that menopause hormone therapy may influence some aspects of Alzheimer’s pathology, in keeping with previous evidence that women who take hormones during the menopause transition or soon after may experience greater brain-protective benefits as compared to those who start taking hormones later in life,” said Lisa Mosconi, of Weill Cornell Medicine in New York City, who was not involved with the study.

The new research seems to contradict the conclusion of the famous Women’s Health Initiative (WHI) two decades ago that found HRT use was associated with a two-fold higher incidence of probable dementia compared to placebo, but experts say that this may be because the participants started therapy well after menopause.

“When it comes to hormone therapy timing is everything,” said Dr. JoAnn Manson, coauthor of the new study who was also a lead investigator with the WHI. “Our previous findings from the WHI suggested that starting hormone therapy early in menopause, rather than late initiation, provides better outcomes for heart disease, cognitive function, and all-cause mortality — and this study suggests it it’s the same for tau deposition.”