Early menopause may lead to some women developing dementia, scientists say

‘Hormone therapy should be administered close to menopause onset, but not several years after’

Early age at menopause may be a factor behind some women developing Alzheimer’s disease, according to a new study which says hormone therapy may help reduce the risk.

The research, published on Monday in the journal JAMA Neurology, shed light on the relationship between the risk of Alzheimer’s disease (AD) and age of menopause and use of hormone therapy (HT).

“HT 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 HT affects the brain,” study corresponding author Rachel Buckley said in a statement.

“We found that the highest levels of tau, a protein involved in Alzheimer’s disease, were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of hormone therapy,” Dr Buckley said.

Researchers say premature menopause, which occurs either spontaneously before the age of 40 or due to surgical intervention before the age of 45, is associated with increased risk of AD dementia.

While HT has been shown to improve many severe symptoms related to menopause and hypothesised to prevent cognitive impairment, a previous study also found that hormone therapy may be associated with higher incidence of dementia.

However, scientists say this could have possibly been due to the initiation of HT many years after menopause onset in the earlier study.

In the new study, researchers used positron emission tomography (PET) brain imaging scans to analyse how the presence of two proteins involved in AD dementia, β-amyloid and tau, related to age at menopause and HT use.

“Our previous findings from the WHI suggested that starting HT 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,” JoAnn Manson, another author of the study, said.

Scientists assessed PET scans from 292 cognitively unimpaired adults to determine levels of amyloid and tau in seven regions of the brain.

They found that women had greater levels of tau compared to men of the same age, especially in cases where they also had elevated β-amyloid.

Researchers also found that the link between abnormal levels of β-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.

They observed that tau levels were particularly high in the entorhinal and inferior temporal regions – located close to the memory-center of the brain and are known to be involved in the progression of AD dementia.

Scientists also discovered that the late initiation of HT – five years or more after menopause – was linked to β-amyloid and tau formation.

In further studies, researchers hope to assessed sex-specific risk factors for AD dementia by analyzing biological signatures, including sex hormones, in blood plasma and on the X-chromosome.

“Up to 10 per cent of women experience premature or early menopause, and our findings suggest that earlier age at menopause may be a risk factor for AD dementia,” study first author Gillian Coughlan said.

“Hormone therapy can have negative effects on cognition, but only if initiated several years after age at menopause. These observational findings support clinical guidelines that state hormone therapy should be administered close to menopause onset, but not several years after,” Dr Coughlan said.