What Drives Alzheimer’s in Women?
Female sex, early age at menopause, and hormone treatment use just about every have been involved with better regional tau in cognitively usual people with elevated beta-amyloid, cross-sectional PET data confirmed.
The greatest degrees of tau were being viewed in hormone remedy end users who experienced a delay of additional than 5 many years involving menopause onset and the get started of hormone treatment, reported Rachel Buckley, PhD, of the Massachusetts Typical Clinic in Boston, and co-authors in JAMA Neurology.
“While a truthful amount of money of scientific studies have focused on the outcomes of menopause and hormone remedy on threat of dementia, considerably fewer research rigorously analyzed their affiliation with Alzheimer’s disorder biomarkers, particularly amyloid and tau, in clinically usual older women,” Buckley claimed.
“This is critical to know presented that it continue to remains unclear what could be the driving system of the menopause changeover, and any use of hormone substitute, on risk for dementia,” she informed MedPage Right now.
“Counterintuitively, we discovered that gals with elevated amyloid who described having hormone therapy also showed greater tau load,” Buckley pointed out. “A single would have imagined taking hormone remedy might ameliorate the problems of missing estrogen because you are reintroducing estrogen into the system.”
“But this is where it got attention-grabbing: following more investigation into this group of women of all ages who described getting hormone treatment, we uncovered that greater threat was only affiliated with those people girls who had a lengthy hole involving their menopause onset and hormone remedy initiation — higher than 5 or 6 yrs,” Buckley explained. “It would seem that introduction of exogenous estrogens soon after a lengthy pause is not a good notion.”
The results include to an raising body of literature indicating that menopause — specially early or untimely menopause — is a contributor to women’s increased lifelong threat of Alzheimer’s disease, famous Lisa Mosconi, PhD, of Weill Cornell Medicine in New York Town, who was not concerned with the research.
“This examine also suggests that menopause hormone therapy may possibly impact some features of Alzheimer’s pathology, in retaining with previous evidence that women of all ages who consider hormones during the menopause transition or shortly right after may perhaps experience better brain-protective advantages as compared to all those who start out taking hormones afterwards on in lifetime,” Mosconi advised MedPage Right now. “Total, the link amongst menopause and Alzheimer’s disease has been disregarded for much far too extended, even with its possible significance.”
Premature menopause — which can be either spontaneous or the consequence of surgical intervention prior to age 40 or 45, respectively — occurs in 1% to 10% of women and has been associated with worse dementia outcomes.
Early studies had suggested that hormone treatment may ameliorate cognitive impairment in menopausal or postmenopausal ladies, Buckley and colleagues famous. On the other hand, 2 a long time in the past, the seminal Women’s Wellbeing Initiative (WHI) analyze located that HT use was connected with about 2-fold larger incidence of possible dementia relative to placebo, maybe because of to initiating hormone therapy several years just after menopause onset.
“When it comes to hormone treatment, timing is everything,” co-creator JoAnn Manson, MD, DrPH, who also was a direct investigator on the WHI, said in a assertion. “Our preceding results from the WHI proposed that setting up hormone treatment early in menopause, relatively than late initiation, presents better outcomes for heart disorder, cognitive purpose, and all-bring about mortality — and this study suggests that the same is accurate for tau deposition.”
Buckley and colleagues utilized info from the Wisconsin Registry for Alzheimer’s Avoidance (WRAP), evaluating PET scans of 292 cognitively unimpaired grown ups (193 gals and 99 men) to decide amyloid and tau stages in seven mind areas. Suggest age was 67.4 at tau scan 52 participants had abnormal amyloid-beta and 106 ended up APOE4 carriers. A overall of 98 ladies ended up earlier or latest hormone therapy end users. Facts had been collected in between November 2006 and May well 2021. Age at menopause and use of hormone remedy were self-reported.
Amongst participants with elevated amyloid, woman sexual intercourse (standardized β=−0.41, P<0.001), earlier age at menopause (standardized β=−0.38, P<0.001), and hormone therapy use (standardized β=0.31, P=0.008) were associated with higher regional tau PET compared with male sex, later age at menopause, and nonuse of hormone therapy. Medial and lateral regions of the temporal and occipital lobes were affected.
Initiating hormone therapy more than 5 years after menopause onset 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, APOE4, cardiovascular disease risk, menopause symptom severity, and menopause-related sleep problems.
The study had several limitations, Buckley and co-authors acknowledged. The researchers didn’t know what precipitated premature menopause or why women chose to start hormone therapy both factors may have influenced the findings. In addition, most people in the study were white.
The WRAP study is supported by the NIH.
Buckley is supported by a Pathway to Independence award and an Alzheimer’s Association research fellowship. Co-authors reported relationships with the NIH, Fonds National de la Recherche Scientifique, WelBio, Biogen, Roche, Mars Edge, AC Immune, Alector, Genentech, Janssen, Neuraly, Oligomerix, Prothena, Renew, Alnylam, Cytox, JOMDD, NervGen, Neurocentria, Shionogi, Vigil Neuroscience, Ionis, Acumen, Vaxxinity, Eisai, Eli Lilly, Alzheimer’s Association, Roche Diagnostics, and Cerveau Technologies.
Source Reference: Coughlan GT, et al “Association of age at menopause and hormone therapy use with moderate tau and β-amyloid positron emission tomography” JAMA Neurol 2023 DOI: 10.1001/jamaneurol.2023.0455.