Women are more likely than men to develop Alzheimer’s disease (AD), making up two-thirds of patients. A new study found that the early age of menopause may be a risk factor for AD dementia, but women who were prescribed hormone therapy (HT) around the age of onset of menopause did not present an increased risk, according to its authors published in the journal ‘JAMA Neurology’.
“HT is the most reliable way to relieve severe menopausal symptoms, but how it affects the brain has not been clear in recent decades,” says study author Dr. Rachel Buckleyof the Department of Neurology at Massachusetts General Hospital (MGH), a founding member of the health system Mass General Brigham (U.S).
“We found that the highest levels tau Altos, a protein implicated in Alzheimer’s disease, have only been seen in users of hormone therapy who declared a long delay between the age of onset of menopause and the start of hormone therapy -continues-. The idea that tau deposition may underlie the association between late intervention of hormone therapy and dementia of Alzheimer’s disease was a major discovery, something that had not been seen before.”
Early menopause, defined as that which occurs spontaneously before age 40 or due to surgery before age 45, has been associated with an increased risk of AD dementia.
HT improves many serious menopause-related symptoms and has been hypothesized to prevent menopause as well. cognitive decline. However, two decades ago, the seminal study Women’s Health Initiative (WHI) found that HT use was associated with a almost twice as high incidence of dementia compared to placebo among women aged 65 years and older, possibly due to initiation of HT many years after onset of menopause.
To better understand these findings, Buckley and his colleagues used computed tomography neuroimaging. positron emission (PET) to study how the presence of two proteins involved in AD dementiabeta-amyloid and tau, was related to age at menopause and HT use.
Although previous studies have examined the symptoms of cognitive decline in menopausal women, few investigations have examined the biological factors underlying these changes, which may be at play in determining the risk of developing the disease. Alzheimer’s disease.
“When it comes to hormone therapy, timing is everything,” said co-author JoAnn Manson, a WHI principal investigator and head of the Division of Preventive Medicine at Brigham and Women’s Hospitalfounding member of the Mass General Brigham Health System.
“Our previous WHI findings suggested that the onset of HT at the onset of menopauserather than late onset, it provides better outcomes for heart disease, cognitive function, and all-cause mortality, and this study suggests the same is true for tau deposition.”
The researchers used data from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), one of the few longitudinal studies of AD dementia that includes detailed information on menopause and HT use, as well as PET neuroimaging.
They analyzed the scanners PET from 292 adults without cognitive impairment to determine the amyloid and tau levels in seven brain regions. Tau, which is known to be present in greater amounts in females than males in these brain regions, was the main objective of the investigationbecause its presence can offer a vision of the sex-specific aspects in AD dementia and the risks that women may experience post menopausebefore they even begin to show symptoms of cognitive decline.
As expected, women had higher levels of tau than men of the same age, especially when they also had elevated beta amyloid. But the researchers also found that the association between abnormal beta-amyloid levels and tau was much stronger in women with early menopause, even after adjusting for known causes of premature menopausesuch as smoking and oophorectomy, and even due to genetic risk factors for AD dementia.
In particular, tau levels were elevated in the entorhinal and inferior temporal regionswhich are located near the memory center of the brain and are known to be involved in the progression of AD dementia.
As HT is used by many women going through premature menopause, the researchers examined whether its use was associated with beta-amyloid and tau. While they confirmed this association, they found that starting HT late – five years or more after menopause – led to this. relationship. Many women in the late-onset HT group began using it nearly a decade after menopause.
In the future, researchers will continue to study gender-specific risk factors for AD dementia using the biosignature analysisincluding sex hormones, in andthe blood plasma It is on the X chromosome.
They will also continue their efforts to identify sex-specific risk factors for AD dementia and are working to understand the unique role tau plays in women compared to men, its impact on the brain and why the early menopause and late onset of HT may be associated with increased tau, even in cognitively healthy women.
“Up to 10% of women experience premature or early menopause, and our findings suggest that earlier age at menopause may be a risk factor for AD dementia,” explains first author Gillian Coughlan of the Department of Neurology at MGH-. Hormone therapy can have negative effects on cognition, but only if started several years after menopausal age.”
As he points out, “these observational findings support the clinical guidelines who state that hormone therapy should be administered close to the onset of menopausebut not several years later.