Women are more likely than men to develop Alzheimer’s disease (AD), with women accounting for two-thirds of the population living with AD. A new study, led by Mass General Brigham researchers, has claimed a relationship between the risk of Alzheimer’s disease and the age of menopause and the use of hormone therapy (HT).
The results, published in JAMA Neurology, suggest that early age at menopause may be a risk factor for AD dementia, but that women prescribed HT around the age of menopause did not show an increased risk.
Author Rachel Buckley, PhD, of the Massachusetts Department of Neurology says “HT is the most reliable way to relieve severe menopausal symptoms, but for the past few decades it has been unclear how HT affects the brain”.
Early menopause
Premature menopause, defined as menopause occurring spontaneously before age 40 or as a result of surgery before age 45, is associated with an increased risk of AD dementia. HT improves many severe symptoms associated with menopause and is also thought to prevent cognitive impairment.
However, two decades ago, a pivotal Women’s Health Initiative (WHI) study found that HT use was associated with nearly twice the incidence of dementia compared to placebo in women aged 65 and older, likely due to HT initiation. many years after the onset of menopause.
To better understand these findings, Buckley and colleagues used positron emission tomography (PET) neuroimaging to study how the presence of two proteins involved in AD dementia, α-amyloid and tau, was related to age at menopause and HT use.
PET scans from 292 adults with cognitive impairment
The researchers used data from the Wisconsin Registry for Alzheimer’s Disease Prevention (WRAP), one of the few longitudinal studies on AD dementia that includes detailed information on menopause and HT use, as well as PET neuroimaging. They analyzed PET scans from 292 adults with cognitive impairment to determine levels of amyloid and tau in seven brain regions.
Tau, which is known to be present in greater amounts in these brain regions in women than in men, was a primary focus of the research because its presence may offer insight into sex-specific aspects of AD dementia and the risks that postmenopausal women may experience even before they start showing symptoms of cognitive decline.
As expected, women had higher levels of tau compared to age-matched men, especially when they also had elevated β-amyloid. However, the researchers also found that the association between abnormal levels of β-amyloid and tau was much stronger in women who had an earlier onset of menopause, even after adjusting for known causes of early menopause, such as smoking and oophorectomy, and even for genetic risk factors factors. AD dementia.
In the future, researchers are continuing to study sex-specific risk factors for AD dementia by analyzing biological signatures, including sex hormones, in blood plasma and on the X-chromosome. They also continue to try to understand the unique role that tau plays in women compared to men, its impact on the brain, and why earlier menopause and late initiation of HT may be associated with increased tau, even in women with cognitive impairment.
“Up to 10 percent of women experience premature or early menopause, and our findings suggest that earlier age at menopause may be a risk factor for AD dementia,” said first author Gillian Coughlan, PhD, of the MGH Department of Neurology. “Hormonal therapy can have a negative effect on cognition, but only if it is started several years after the age of menopause.
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