The study showed that the highest levels of tau, a protein involved in Alzheimer`s, were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of the therapy

Those who were prescribed hormone therapy around the age of menopause onset did not show increased risk, Image Courtesy: iStock

A new study has found that women who have early menopause may be at high risk of developing Alzheimer*s disease, but those who were prescribed hormone therapy around the age of menopause onset did not show increased risk.

Premature menopause, defined as menopause that occurs spontaneously before the age of 40 or due to surgical intervention before the age of 45, has been associated with increased risk of Alzheimer*s disease. Hormone therapy improves many severe symptoms related to menopause and has been hypothesised to also prevent cognitive impairment.

The study, published in JAMA Neurology, showed that the highest levels of tau -- a protein involved in Alzheimer*s -- were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of the therapy.

Administering hormone therapy close to menopause onset provided better cognition.

"When it comes to hormone therapy, timing is everything," said JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women*s Hospital.

"Our previous findings 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 that the same is true for tau deposition," Manson said.

In the study, the team used positron emission tomography (PET) neuroimaging scans from 292 people to study how the presence of two proteins involved in Alzheimer*s, beta-amyloid and tau, related to age at menopause and hormone therapy use. Tau is known to be present in greater quantities in women compared to men.

The PET scan results also showed that women had greater levels of tau compared to men of the same age, especially in cases where they also had elevated beta-amyloid.

But the researchers also found that the association between abnormal levels of beta-amyloid and tau was much stronger in women who had earlier menopause onset, even after adjusting for known causes of premature menopause, such as smoking and oophorectomy, and even genetic risk factors for Alzheimer*s.

Notably, tau levels were high in the entorhinal and inferior temporal regions, which are located close to the memory-centre of the brain and are known to be involved in the progression of Alzheimer*s.

"Hormone therapy is the most reliable way to ameliorate severe menopause symptoms, but over the last few decades, there has been a lack of clarity on how hormone therapy affects the brain," said Rachel Buckley, from the Department of Neurology at Massachusetts General Hospital (MGH).

"The idea that tau deposition may underlie the association between late hormone therapy intervention and Alzheimer*s was a huge finding, something that hadn*t been seen before," Buckley added.

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