” HT is the most reliable method to ameliorate extreme menopause symptoms, but over the last couple of years, there has actually been a lack of clarity on how HT affects the brain,” stated corresponding author Rachel Buckley, Ph.D., of the Department of Neurology at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “We discovered that the highest levels of tau, a protein included in Alzheimers disease, were only observed in hormone treatment users who reported a long hold-up in between age at menopause onset and their initiation of hormonal agent therapy. The idea that tau deposition may underlie the association between late hormone therapy intervention and Alzheimers illness dementia was a big finding, something that had not been seen before.”
Early menopause, specified as menopause that happens spontaneously prior to the age of 40 or due to surgical intervention before the age of 45, has actually been connected with an increased threat of AD dementia. HT enhances lots of serious symptoms connected to menopause and has been assumed to also prevent cognitive problems. 2 years back, the critical Womens Health Initiative (WHI) research study found that HT use was associated with an almost two-fold higher occurrence of dementia compared to a placebo amongst females aged 65 years and older, perhaps due to the initiation of HT lots of years after menopause start.
To much better comprehend these findings, Buckley and colleagues utilized positron emission tomography (PET) neuroimaging to study how the existence of two proteins included in AD tau, dementia, and β-amyloid, associated to age at menopause and HT usage. While previous studies taken a look at symptoms of cognitive decline in menopausal females, few examinations analyzed the biological factors underlying these modifications, which may be at play in determining risk of Alzheimers disease.
” When it concerns hormonal agent therapy, timing is everything,” said co-author JoAnn Manson, MD, MPH, DrPH, among the lead detectives of the WHI and chief of the Division of Preventive Medicine at Brigham and Womens Hospital, a founding member of the Mass General Brigham healthcare system. “Our previous findings from the WHI suggested that beginning HT early in menopause, rather than late initiation, supplies better outcomes for heart disease, cognitive function, and all-cause mortality– and this study recommends that the very same holds true for tau deposition.”
The researchers used information from the Wisconsin Registry for Alzheimers Prevention (WRAP), among the couple of longitudinal studies on advertisement dementia that consists of in-depth details on menopause and HT use as well as PET neuroimaging. They examined PET scans from 292 cognitively unimpaired adults to determine levels of amyloid and tau in 7 regions of the brain. Tau, which is known to be present in higher amounts in females compared to males in these brain areas, was the main focus of the examination, as its presence may offer insight into the sex-specific aspects of AD dementia and the threats that post-menopausal women may experience, even prior to they begin to display signs of cognitive decline.
As expected, women had higher levels of tau compared to men of the exact same age, particularly in cases where they also had raised β-amyloid. The scientists likewise found that the association in between abnormal levels of β-amyloid and tau was much stronger in ladies who had earlier menopause onset, even after changing for recognized causes of early menopause, such as smoking and oophorectomy, and even hereditary danger aspects for AD dementia.
Given that lots of females who go through early menopause usage HT, the scientists took a look at whether HT use was associated with β-amyloid and tau. Many women in the late-HT-initiation group started HT close to a decade after menopause.
Moving forward, the researchers are continuing to study sex-specific danger factors for AD dementia by evaluating biological signatures, including sex hormones, in blood plasma and on the X-chromosome. They are also continuing to participate in efforts to comprehend the distinct function that tau plays in women compared to males, its effect on the brain, and why earlier menopause and late HT initiation might be related to increased tau, even in cognitively unimpaired women.
” Up to 10 percent of ladies experience premature or early menopause, and our findings recommend that earlier age at menopause might be a risk factor for advertisement dementia,” said very first author Gillian Coughlan, Ph.D., of the MGH Department of Neurology. “Hormone treatment can have negative impacts on cognition, however only if started several years after age at menopause. These observational findings support scientific standards that state hormone therapy need to be administered near to menopause beginning, but not numerous years after.”
Reference: “Association of Age at Menopause and Hormone Therapy Use With Tau and β-Amyloid Positron Emission Tomography” by Gillian T. Coughlan, MS, Ph.D., Tobey J. Betthauser, Ph.D., Rory Boyle, Ph.D., Rebecca L. Koscik, Ph.D., Hannah M. Klinger, MS, Lori B. Chibnik, Ph.D., MPH, Erin M. Jonaitis, Ph.D., MS, Wai-Ying Wendy Yau, MD, Allen Wenzel, BS, Bradley T. Christian, Ph.D., Carey E. Gleason, Ph.D., Ursula G. Saelzler, Ph.D., Michael J. Properzi, BEng, BCompSci, Aaron P. Schultz, Ph.D., Bernard J. Hanseeuw, MD, Ph.D., JoAnn E. Manson, MD, DrPH, MACP, Dorene M. Rentz, PsyD, Keith A. Johnson, MD, Reisa Sperling, MD, Sterling C. Johnson, Ph.D. and Rachel F. Buckley, Ph.D., 3 April 2023, JAMA Neurology.DOI: 10.1001/ jamaneurol.2023.0455.
The primary WRAP research study is supported by R01AG027161 with extra financing for imaging from R01AG021155, P50 AG033514, S10 OD025245, U54 HD090256 and with resources and the usage of facilities at the Madison VA Hospital and Geriatric Research, Education and Clinical. Coughlan is support by a postdoctoral fellowship award from the Alzheimers Society of Canada (22-08). Buckley is supported by a Pathway to Independence award (R00AG061238) and an Alzheimers Association Research Fellowship (AARF-20-675646).
” HT is the most trusted method to ameliorate severe menopause symptoms, however over the last few years, there has been a lack of clarity on how HT impacts the brain,” stated matching author Rachel Buckley, Ph.D., of the Department of Neurology at Massachusetts General Hospital (MGH), an establishing member of the Mass General Brigham health care system. Early menopause, defined as menopause that occurs spontaneously prior to the age of 40 or due to surgical intervention prior to the age of 45, has actually been associated with an increased threat of Advertisement dementia. 2 decades back, the critical Womens Health Initiative (WHI) study found that HT usage was associated with a nearly two-fold greater occurrence of dementia compared to a placebo amongst females aged 65 years and older, perhaps due to the initiation of HT numerous years after menopause beginning.
Offered that many ladies who undergo early menopause use HT, the scientists examined whether HT use was associated with β-amyloid and tau.” Up to 10 percent of ladies experience early or early menopause, and our findings suggest that earlier age at menopause may be a risk element for Advertisement dementia,” stated first author Gillian Coughlan, Ph.D., of the MGH Department of Neurology.
Alzheimers is a progressive brain disease that impacts memory, thinking, and behavior. It is the most common cause of dementia among older grownups and is identified by the decline in cognitive function and the ability to perform day-to-day activities.
When begun close to the onset of menopause, Research carried out by Mass General Brigham supports medical guidelines that show starting hormonal agent therapy is safer.
Women have a higher possibility of establishing Alzheimers disease (ADVERTISEMENT) compared to males, consisting of two-thirds of the people affected by advertisement. A current research study performed by researchers from Mass General Brigham has exposed insights into the connection between Alzheimers disease risk, age at menopause, and hormonal agent therapy (HT) use.
The findings, published in JAMA Neurology, recommend that an early start of menopause might contribute to a heightened risk for AD dementia. The research study also discovered that ladies who got HT around the time of menopause start did not display an increased threat.