A persistent enigma in Alzheimer’s research is why women are more prone to developing the disease and other forms of dementia compared to men. Some researchers propose that the significant hormonal shifts women undergo during menopause might be a contributing factor. However, the exact mechanism by which menopause may lead to dementia in some individuals remains elusive.
Recent studies published this week propose that the timing of menopause onset and the promptness of hormone therapy intervention could significantly influence cognitive decline.
One study, published on Wednesday in Alzheimer’s & Dementia, examined over 180,000 postmenopausal women in the U.K. Those undergoing hormone replacement therapy (HRT) experienced a 10% reduction in the risk of all types of dementia and a 16% reduction in Alzheimer’s risk specifically, over a 13-year follow-up. These findings persisted even when adjusting for ethnicity, smoking, education, and other factors.
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According to Anne-Marie Minihane, the study’s co-senior author and a professor of nutrigenomics at the University of East Anglia, this research is the “most comprehensive analysis in this space to date.”
Interestingly, women who had surgical menopause, resulting from a hysterectomy or oophorectomy, showed a more significant response to HRT, with a 26% reduction in dementia risk. Additionally, starting HRT between the ages of 46 and 56 was linked to a lower dementia risk compared to starting treatment later.
Minihane notes that the study is not a clinical trial and doesn’t establish HRT as a protective measure against dementia or Alzheimer’s. Instead, it highlights a notable correlation between menopause treatment and dementia risk, contributing to the growing evidence of menopause’s role in cognitive decline.
The second study, published on Tuesday in JAMA Network Open, provides further insights. It revealed that earlier onset of menopause is associated with greater likelihood of cognitive decline and earlier Alzheimer’s diagnosis. This trend was particularly pronounced in women who underwent surgical menopause.
“It confirms that women who’ve had surgical menopause and who’ve had menopause early are a group who really need attention,” Minihane states, referring to the JAMA Network Open study’s outcomes.
The study also found that women with earlier menopause experienced faster accumulation of “white matter hyperintensity” volume, a brain tissue damage marker. This effect was more common in women who experienced natural menopause.
“There is a fairly well-established link between earlier age at menopause and risk of cognitive decline,” says Riley Bove, the JAMA Network Open study’s senior author and a neurology professor at the University of California, San Francisco. “What this study adds is that we detected a lasting trace of menopause on women’s brains even decades later.”
Minihane suggests that the critical nature of women who had a hysterectomy or oophorectomy might be due to shorter lifetime estrogen exposure or the common use of estrogen-only HRT in these cases, which might affect outcomes.
Indeed, earlier research this month involving thousands of women who donated their brains for science found that estrogen-only HRT was linked to a reduced risk of Alzheimer’s.
These findings collectively suggest that Alzheimer’s prevention might need to begin well before old age, offering a “window of opportunity” for early intervention, according to Minihane.
However, she warns that more research is necessary to confirm these observations, as evidence remains mixed. Previous studies indicated that combined hormone therapy could increase dementia risk in individuals over 65, while others found little to no effect from HRT.
Riley Bove points out that it’s uncertain how much these conflicting results are due to study design flaws, trial durations, biological differences, or other factors. “I hope we can continue to see large and well-designed studies such as the current one [in Alzheimer’s & Dementia] add much needed evidence to the field of women’s health.”
Minihane hopes to conduct a clinical trial to explore how HRT might impact Alzheimer’s characteristics. She also aims to research how menopause affects the brain and whether phytoestrogen-rich foods, like soybeans, could support cognitive health.
“We have a long way to go,” Minihane says. “Potentially, at some time in the future, [HRT] may be recommended as a treatment for reducing lifetime risk of dementia. But I think a lot more research needs to be done before we’re even close to getting to that point.”
