What Causes Alzheimer’s Disease in Women?

Cross-sectional PET data showed that female sex, younger age at menopause, and use of hormone therapy were each associated with elevated regional tau levels in cognitively normal individuals with elevated beta-amyloid. I was.

The highest levels of tau were found in hormone therapy users who had a delay of 5 years or more from the onset of menopause to the start of hormone therapy, reported Rachel Buckley, Ph.D., of Massachusetts General Hospital in Boston, co-authors. Department of Neurology, JAMA.

“Although a considerable amount of research has focused on the effects of menopause and hormone therapy on dementia risk, the association of biomarkers of Alzheimer’s disease, namely amyloid and tau, in clinically normal older women has been unresolved.” Far fewer studies have rigorously tested

“Considering the risk of dementia, knowing what the driving mechanisms of the menopausal transition are and the use of hormone replacement remains unclear, this is very important to know. MedPage Today.

“Counterintuitively, we found that women with elevated amyloid who reported taking hormone therapy also had higher tau loads,” Buckley noted. So one might imagine that taking hormone therapy might remedy the problem of lost estrogen.”

“But here’s where it gets interesting. Further investigation of this group of women who reported receiving hormone therapy showed that the higher risk was in women who had a long gap between the onset of menopause and the start of hormone therapy.” We found that it was only relevant for more than 5 or 6 years,” said Buckley. “Introducing exogenous estrogen after a long pause doesn’t seem like a good idea.”

The findings point to a growing body of literature showing that menopause, especially premature menopause or premature menopause, contributes to a higher lifetime risk of Alzheimer’s disease in women, said Weill Cornell of New York City. Dr. Lisa Mosconi of Medicine pointed out. Not involved in her research.

“This study also shows that menopausal hormone therapy may affect several aspects of Alzheimer’s disease pathology. This is consistent with previous evidence that women who take the hormone may experience greater cerebral protective effects compared to women who start taking the hormone later in life,” Moscone said. MedPage Today“Overall, the relationship between menopause and Alzheimer’s disease has been overlooked for too long, despite its potential importance.”

Premature menopause can be the result of voluntary or surgical intervention before age 40 or 45, respectively. 1% to 10% Female Worse dementia outcome.

Earlier studies suggested that hormone therapy might improve cognitive impairment in menopausal or postmenopausal women, Buckley and colleagues noted.But 20 years ago, ingenious Women’s Health Initiative (WHI) study found that HT use was associated with approximately two-fold. more likely to have dementia This is probably because hormone therapy was started many years after the onset of menopause compared to placebo.

“When it comes to hormone therapy, timing is everything,” co-author JoAnn Manson, MD, DrPH, who was also a WHI principal investigator, said in a statement. It suggests that early onset rather than late onset has better outcomes for heart disease, cognitive function, and all-cause mortality, and this study does the same for tau deposition. suggests that this is the case.”

Buckley and colleagues used data from the Wisconsin Registry for Alzheimer’s disease prevention (Wrap), PET scans of 292 adults (193 females, 99 males) without cognitive impairment were evaluated to determine amyloid and tau levels in seven regions of the brain. Mean age at tauscan was 67.4 years. 52 participants had abnormal amyloid beta and 106 had abnormal APOE4 career. A total of 98 women were past or current hormone therapy users. Data were collected between November 2006 and May 2021. Age at menopause and use of hormone therapy were self-reported.

Among participants with elevated amyloid, female sex (standardized β = -0.41, P.<0.001), earlier menopausal age (standardized β=-0.38, P.<0.001), and use of hormone therapy (standardized β=0.31, P.=0.008) were associated with higher local tau PET, later age at menopause, and lack of hormone therapy compared with men. The medial and lateral regions of the temporal and occipital lobes were affected.

Hormone therapy initiated at least 5 years postmenopausal was associated with higher tau PET compared with early hormone therapy (β=0.49, P.= 0.001). Overall findings remained after adjusting for years of education. APOE4risk of cardiovascular disease, severity of menopausal symptoms, and menopausal-related sleep disturbances.

Buckley and co-authors acknowledge that the study had some limitations. Researchers didn’t know what caused premature menopause or why women chose to start hormone therapy. Both factors may have influenced the findings. Additionally, most of the people who participated in the study were Caucasian.