For women, greater exposure to estrogen in life may protect brain
regions that are vulnerable to Alzheimer's

Date:
November 4, 2021
Source:
Weill Cornell Medicine
Summary:
The drop in estrogen levels that occurs with menopause brings
declines in the volumes of 'gray matter,' the cellular matter of the
brain, in key brain regions that are also affected in Alzheimer's
disease. But a new study suggests that greater cumulative exposure
to estrogen in life, for example from having had more children
or from having taken menopause hormone therapy, may counter this
brain-shrinking effect.



FULL STORY ==========================================================================
The drop in estrogen levels that occurs with menopause brings declines
in the volumes of "gray matter," the cellular matter of the brain, in
key brain regions that are also affected in Alzheimer's disease. But a
new study from Weill Cornell Medicine researchers, in collaboration with
the University of Arizona, suggests that greater cumulative exposure to estrogen in life, for example from having had more children or from having taken menopause hormone therapy, may counter this brain-shrinking effect.


==========================================================================
The findings, reported Nov. 3 in Neurology, come from an analysis of
personal histories, MRI scans and cognitive tests on 99 women in their
late 40s to late 50s. The researchers confirmed an earlier finding
linking menopause to lower gray matter volume (GMV) in brain areas that
are also vulnerable to Alzheimer's. But they also linked indicators of
higher overall estrogen exposure, such as a longer span of reproductive
years (menarche to menopause), more children and the use of menopause
hormone therapy and hormonal contraceptives, to higher GMV in some of
these brain areas.

The study was an observational study rather than a clinical trial, but
it adds to the evidence that estrogen may have a protective effect on
the female brain, limiting the loss of gray matter that normally comes
with menopause, and thereby potentially reducing Alzheimer's risk.

"Our findings suggest that while the menopause transition may bring vulnerability for the female brain, other reproductive history events indicating greater estrogen exposure bring resilience instead," said study senior author Dr. Lisa Mosconi, an associate professor of neuroscience
in neurology at Weill Cornell Medicine and director of the Women's
Brain Initiative, and associate director of the Alzheimer's Prevention
Clinic at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell
Medical Center.

Researchers estimate that nearly two thirds of those living with
Alzheimer's in the United States are women. The higher prevalence of Alzheimer's in women may be due in part to women's greater longevity,
among other reasons. A leading hypothesis is that that vulnerability
relates to estrogen.

Receptors for estrogen molecules are found in cells throughout women's
brains, and the sex hormone has long been known not just to help steer
brain development and behavior but also generally to have a nourishing
and protecting role in the central nervous system. That protection
doesn't last forever, though. Estrogen levels decline steeply during the transition through menopause, and as recent research from Dr. Mosconi
and others has shown, women tend to experience significant GMV loss
during this transition.

The volume loss occurs especially in brain regions that are the most
heavily affected in Alzheimer's, and at roughly the same time of life
when the long, slow process of late-onset Alzheimer's is believed to
start. Thus, women's mid- life loss of estrogen may be a key factor
behind the higher risk of Alzheimer's.

The flip side of this hypothesis is that more estrogen, in particular a cumulatively greater estrogen exposure, could serve as a counter to the
brain- weakening effect of menopause. That possibility is what Dr. Mosconi
and her team sought to investigate in the new study.

The analysis covered 99 women aged 46-58 and a comparison group
of 29 similarly aged men. It confirmed that the post-menopausal
and peri-menopausal (starting menopause) women, compared with the pre-menopausal women and the men, had significantly lower GMV --
adjusted for age and head size -- in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions, which are heavily affected
by Alzheimer's.

By contrast, among the women, having more estrogen exposure as implied
by various factors was associated with greater GMV in certain brain
areas. Longer reproductive span, for example, was significantly linked
to more GMV in a cluster of regions near the top of the brain including
the superior parietal lobule and precuneus of the left hemisphere. Having
had more children was significantly associated with more GMV in inferior
and middle frontal gyri, and middle and inferior temporal gyri. Having
used hormone replacement therapy was associated with more GMV in superior frontal gyrus and several other brain regions. All these brain regions
are known to be affected by aging and Alzheimer's.

The results support the idea that estrogen can be protective, the
researchers say, and suggest that further investigation of the specific biological pathways underlying this effect could yield medical or
lifestyle changes that help women reduce their risk of cognitive decline
with aging as well as Alzheimer's dementia risk.

"We're hoping now to get further into the details of these links between estrogen and GMV, for example by comparing the effects of surgical
menopause and spontaneous menopause, and by focusing specifically on
certain types of estrogen exposure, such as menopause hormone therapy,"
said study first author Eva Schelbaum, research assistant in Dr. Mosconi's laboratory. "The goal as always is to understand why Alzheimer's affects
more women than men, and how we can reduce that risk.

========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Eva Schelbaum, Lacey Loughlin, Steven Jett, Cenai Zang, Grace Jang,
Niharika Malviya, Hollie Hristov, Silky Pahlajani, Richard Isaacson,
Jonathan P Dyke, Hooman Kamel, Roberta Diaz Brinton, Lisa Mosconi.

Association of Reproductive History With Brain MRI
Biomarkers of Dementia Risk in Midlife. Neurology, 2021;
10.1212/WNL.0000000000012941 DOI: 10.1212/WNL.0000000000012941 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211104140355.htm

--- up 9 weeks, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)