Dubai, United Arab Emirates (CNN) — Alzheimer’s disease affects more women than men, as more than two-thirds of people with severe dementia are female. This may have biological causes that are still poorly understood, according to the Alzheimer’s Association.

Part of the puzzle is that women lose sex hormones, such as estrogen, when they go through menopause, either naturally through a decline in the body’s production of estrogen, or by removing their ovaries through surgery. However, it remains unclear how the loss of these hormones, and the effect of hormone replacement therapy (HRT), affects the risk of dementia.

A new study may reveal a secret or two, as women who menopause early (between 40 and 45), prematurely (before 40), or start HRT more than five years later After menopause, they had higher levels of the protein tau in their brains, according to the study published in JAMA Neurology Monday.

The tangle of tau, along with plaques made up of beta-amyloid proteins, is a hallmark of Alzheimer’s disease.

“This is the first study to show that late use of hormone therapy appears to be associated with increased levels of Alzheimer’s disease markers in the brain,” said Jillian Coughlan, lead author and research fellow in neuroscience at Massachusetts General Hospital in Boston.

However, Coghlan told CNN, these changes only affect women who already have higher levels of beta-amyloid in brain tissue.

“The majority of the associations we saw between menopause and tau occurred in the context of elevated amyloid,” Coughlan said, noting that “a large portion of the older population accumulates amyloid with age, and this is common.”

On the other hand, she noted, deposits of tau protein are uncommon, adding that developing Alzheimer’s disease requires crosslinking of tau and beta-amyloid. “Normally, if you have a combination of beta-amyloid and tau, it generally indicates cognitive decline within a few years,” Coughlan said.

“What we’ve found is that women who go through early menopause, or who use hormone therapy very late, may be at increased risk of developing the disease, but only if they are already in a continuum of Alzheimer’s disease and have elevated levels of amyloid,” she said. They have very low levels of amyloid and experience early menopause, they didn’t have such an association.”

The study also found that women who started hormone therapy “at the appropriate time, around menopause, had neither higher nor lower brain tau proteins.” “This is good because it means we can still use hormone therapy to treat severe menopausal symptoms,” Coghlan said.

Dr. Richard Isaacson, a preventive neurologist for Alzheimer’s disease at the Institute of Neurodegenerative Diseases, commended the paper’s importance.

“While this is not the first time a study has shown that early HRT may be more protective of a woman’s brain, it has found for the first time that higher amounts of tau may be associated with a delay in starting HRT,” Isaacson, who was not involved in the study, said. .

In contrast, Sarah Imaricio, head of strategic initiatives at Alzheimer’s Research UK, said in a statement: “This study does not show that hormonal therapy causes Alzheimer’s disease. The researchers did not look at whether the participants developed symptoms of dementia, and we cannot be sure of the relationship.” causality in this type of research.

Imaricio, who was not involved in the study, added, “Hormonal therapy has important benefits for many women, helping to combat symptoms that menopause can cause,” adding that “women who are receiving, or considering receiving, hormone therapy should not delay it.” According to these results, anyone concerned regarding the effects of this treatment should speak to their doctor.

Hormone replacement therapy

The menopause stage is defined as when a woman stops menstruating for 12 consecutive months, and the average age of onset of this stage is 51 years, although women can naturally enter menopause between the ages of 40 and 58.

As for the resulting symptoms, they are represented by hot flashes and night sweats that may begin years before, that is, in the premenopausal stage.

Hormone replacement therapy has been an important topic for many women since early and misleading results were published in 2002, from a study called the Women’s Health Initiative Clinical Trial.

This preliminary analysis found that a combination of estrogen and progestin, the type of HRT prescribed at the time, increased the risk of heart disease, as well as stroke, blood clots, dementia and breast cancer.

The repercussions of this were tragic. By the end of the year, the use of hormone therapy had fallen by 30%, and by 2009, the demand for hormone therapy had fallen more than 70%.

Ten years later, the results of the Women’s Health Initiative were reviewed. It turns out that the primary analysis included women 65 and older who were, in fact, at a higher risk of heart attacks, blood clots, and stroke.

The preliminary results for the year 2002 were not correct because they did not take into account the age of the woman at the start of the alternative treatment.

Current medical guidelines suggest that the benefits of hormonal treatment for hot flashes, night sweats, vaginal pain and dryness, trouble urinating, and bone loss outweigh the risks for women under 60 and those with no known or probable history of breast cancer, blood clots, or stroke. stroke, or other contraindications.

What brain scans show

In the new JAMA Neurology study, a team of researchers at Massachusetts General Hospital analyzed the brain scans of 193 women and 99 men with normal cognitive function for amyloid beta and tau buildup.

The study may seem small, but it’s not. “When brain scans are used to study brain disease, that’s a large sample size,” Coughlan said.

Tara Spears-Jones, a professor of neurodegeneration and deputy director of the Center for Discovery of Brain Sciences at the University of Edinburgh in Scotland, who was not involved in the research, said the study found that women had more tau accumulation in several parts of the brain than men of the same age.

“In addition, females have a higher accumulation of tau protein than males when they also have beta-amyloid in the brain,” Spiers-Jones added in a statement.

Coghlan noted that all of the women in the new study used the type of hormonal therapy, the combination of estrogen and progestin, that the women used in the Women’s Health Initiative clinical trial, which has caused a lot of controversy.

“If[our study is replicated]we may have found a potential biological basis for the findings of the Women’s Health Initiative clinical trial, which found that women aged 65 and over were more likely to develop dementia later in life if they took this type of treatment,” Coughlan said. hormonal”.

Experts saw that the study had some limitations, as the majority of the participants were white, and the study did not mention who developed dementia followingward. In addition, not enough people in the study were found to have a genetic risk of Alzheimer’s disease, says Dr Liz Coulthard, assistant professor of dementia and neuroscience at the University of Bristol in the UK, who was not involved in the study.

“We recently discovered that HRT may have different effects on people at high genetic risk (apoE4 positive), but that is not covered here,” Coulthard said in a statement.

“The results are scientifically interesting, but the research into the relationship between HRT, menopause and Alzheimer’s disease is intertwined with the different reasons for which HRT was prescribed, and memory accuracy for menopause,” she added.

“Trialing balanced, effective HRT over many years is the only way we can truly understand if HRT is harmful to brain health,” she concluded.