Menopause causes decreases in the quantities of “gray matter,” the cellular matter of the brain, in important brain regions that are also impacted in Alzheimer’s disease.
However, a new study led by Weill Cornell Medicine researchers in partnership with the University of Arizona reveals that higher lifetime estrogen exposure, such as by having more children or taking menopause hormone therapy, may counteract this brain-shrinking effect.
The findings, published in Neurology on November 3, 2021, are based on a review of 99 women in their late 40s to late 50s’ personal histories, MRI scans, and cognitive tests. Menopause is linked to decreasing gray matter volume (GMV) in brain areas that are also susceptible to Alzheimer’s disease, according to the study.
They also connected increased GMV in several of these brain areas to signs of higher overall estrogen exposure, such as a longer reproductive years (menarche to menopause), more children, and the use of menopause hormone therapy and hormonal contraceptives.
Although the study was not a clinical trial, it adds to the evidence that estrogen may have a protective impact on the female brain, minimizing the loss of gray matter associated with menopause and so potentially lowering 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.
Oestrogens play a role in the development and aging of brain regions important for higher cognitive processes (such as memory) and have been linked to neuropsychiatric illnesses like Alzheimer’s disease. Oestrogens, for example, enhance the density of synaptic and dendritic spines in the hippocampus.
Women account for approximately two-thirds of Alzheimer’s patients in the United States, according to research. Women have a higher frequency of Alzheimer’s disease than men, which could be related to a variety of factors, including their longer lifespan. One popular theory is that the vulnerability is linked to estrogen.
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. The goal as always is to understand why Alzheimer’s affects more women than men, and how we can reduce that risk.
Eva Schelbaum
Furthermore, synaptic spine density is linked to levels of circulating oestradiol. It was unclear until recently how oestrogen-induced dendritic alterations affected neuronal function. There was a positive link between increased cholinergic neurotransmission and longer oestrogen exposure among long-term oestrogen replacement treatment users.
Estrogen receptors may be located in cells all across a woman’s brain, and the sex hormone has long been known to play a feeding and protective role in the central nervous system, in addition to guiding brain growth and behavior.
However, that shield does not last indefinitely. Estrogen levels drop dramatically as women approach menopause, and recent study from Dr. Mosconi and colleagues has found that women lose a significant amount of GMV during this time.
The volume loss occurs in the brain regions most extensively affected by Alzheimer’s disease, and at the same time as the lengthy, gradual process of late-onset Alzheimer’s is thought to begin. As a result, the reduction of estrogen in women in their forties and fifties may be a crucial component in their increased risk of Alzheimer’s disease.
On the other hand, additional estrogen, specifically a progressively higher estrogen exposure, may act as a counterbalance to menopause’s brain-weakening impact. In the latest study, Dr. Mosconi and her colleagues wanted to look into this possibility.
The study included 99 women aged 46 to 58 and a control group of 29 men of the same age. It confirmed that post-menopausal and peri-menopausal (beginning menopause) women had considerably decreased GMV in brain areas such as the hippocampus, entorhinal cortex, and temporal lobe regions, which are extensively affected by Alzheimer’s disease, when compared to pre-menopausal women and men.
Women, on the other hand, who were exposed to more estrogen as a result of numerous circumstances, had higher GMV in particular brain locations. The superior parietal lobule and precuneus of the left hemisphere, for example, were strongly connected to greater GMV in a cluster of brain regions near the top, including the superior parietal lobule and precuneus.
Having more children was linked to higher GMV in the inferior and middle frontal gyri, as well as the middle and inferior temporal gyri. GMV was seen in the superior frontal gyrus and several other brain regions in people who had received hormone replacement treatment. Aging and Alzheimer’s disease have been shown to damage all of these brain regions.
According to the researchers, the findings support the idea that estrogen can be protective and that further research into the specific biological pathways underlying this effect could lead to medical or lifestyle changes that can help women reduce their risk of cognitive decline as they age, 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.”
