What Drives Alzheimer’s in Ladies?

— Tau levels bigger when hormone remedy begins bigger than 5 years after menopause onset

by
Judy George, Deputy Managing Editor, MedPage This day
April 3, 2023

Female sex, early age at menopause, and hormone remedy use every had been connected to bigger regional tau in cognitively identical old folk with elevated beta-amyloid, unhealthy-sectional PET recordsdata confirmed.

The excellent levels of tau had been seen in hormone remedy users who had a prolong of bigger than 5 years between menopause onset and the initiating of hormone remedy, reported Rachel Buckley, PhD, of the Massachusetts Fashioned Health center in Boston, and co-authors in JAMA Neurology.

“Whereas a excellent-making an strive amount of stories contain targeted on the consequences of menopause and hormone remedy on risk of dementia, some distance fewer stories rigorously tested their association with Alzheimer’s illness biomarkers, namely amyloid and tau, in clinically identical old older ladies folk,” Buckley acknowledged.

“Here is serious to know given that it unruffled stays unclear what would be the driving mechanism of the menopause transition, and any use of hormone replacement, on risk for dementia,” she told MedPage This day.

“Counterintuitively, we stumbled on that women folk with elevated amyloid who reported taking hormone remedy furthermore confirmed bigger tau burden,” Buckley identified. “One would contain imagined taking hormone remedy would possibly perchance presumably well ameliorate the considerations with misplaced estrogen on fable of you are reintroducing estrogen into the physique.”

“But right here’s the put it got fascinating: after extra investigation into this neighborhood of girls folk who reported taking hormone remedy, we stumbled on that bigger risk used to be excellent connected to those ladies folk who had a protracted gap between their menopause onset and hormone remedy initiation — bigger than five or six years,” Buckley acknowledged. “Curiously introduction of exogenous estrogens after a protracted quit is now not a big belief.”

The findings add to an increasing physique of literature indicating that menopause — critically early or premature menopause — is a contributor to ladies folk’s bigger lifelong risk of Alzheimer’s illness, smartly-known Lisa Mosconi, PhD, of Weill Cornell Medication in Fresh York Metropolis, who wasn’t eager with the to find.

“This to find furthermore indicates that menopause hormone remedy would possibly perchance presumably well have an effect on some facets of Alzheimer’s pathology, per old proof that women folk who take grasp of hormones sincere thru the menopause transition or soon after would possibly perchance presumably well abilities bigger brain-protective advantages as when put next with folk who start taking hormones afterward in life,” Mosconi told MedPage This day. “General, the connection between menopause and Alzheimer’s illness has been overpassed for lots too long, despite its most likely significance.”

Premature menopause — that can presumably well furthermore be both spontaneous or the raze end result of surgical intervention forward of age 40 or forty five, respectively — occurs in 1% to 10% of girls folk and has been connected to worse dementia outcomes.

Early stories had urged that hormone remedy would possibly perchance presumably well ameliorate cognitive impairment in menopausal or postmenopausal ladies folk, Buckley and colleagues smartly-known. On the opposite hand, 2 decades within the past, the seminal Ladies’s Health Initiative (WHI) to find stumbled on that HT use used to be connected to approximately 2-fold bigger incidence of probable dementia relative to placebo, presumably attributable to initiating hormone remedy decades after menopause onset.

“In the case of hormone remedy, timing is the entirety,” co-author JoAnn Manson, MD, DrPH, who furthermore used to be a lead investigator on the WHI, acknowledged in a observation. “Our old findings from the WHI urged that starting hormone remedy early in menopause, reasonably than unhurried initiation, offers better outcomes for coronary heart illness, cognitive plot, and all-trigger mortality — and this to find suggests that the identical is factual for tau deposition.”

Buckley and colleagues broken-down recordsdata from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), assessing PET scans of 292 cognitively unimpaired adults (193 ladies folk and 99 men) to search out out amyloid and tau levels in seven brain regions. Mean age used to be 67.4 at tau scan; 52 participants had extraordinary amyloid-beta and 106 had been APOE4 carriers. A total of 98 ladies folk had been previous or unusual hormone remedy users. Files had been peaceable between November 2006 and May perchance perchance 2021. Age at menopause and use of hormone remedy had been self-reported.

Amongst participants with elevated amyloid, female sex (standardized β=−0.41, P<0.001), earlier age at menopause (standardized β=−0.38, P<0.001), and hormone remedy use (standardized β=0.31, P=0.008) had been connected to bigger regional tau PET when put next with male sex, later age at menopause, and nonuse of hormone remedy. Medial and lateral regions of the temporal and occipital lobes had been affected.

Initiating hormone remedy bigger than 5 years after menopause onset used to be connected to bigger tau PET when put next with early hormone remedy (β=0.49, P=0.001). General findings remained after adjusting for years of education, APOE4, cardiovascular illness risk, menopause symptom severity, and menopause-connected sleep considerations.

The to find had lots of boundaries, Buckley and co-authors acknowledged. The researchers did not know what precipitated premature menopause or why ladies folk selected to start out hormone remedy; both elements would possibly perchance presumably well contain influenced the findings. As smartly as, most folk within the to find had been white.