Study reveals why women are more likely to develop devastating memory loss and dementia
A drop in estrogen during menopause could be a key driver of higher rates of dementia in women.
Neuroscientists have determined that the drop in the female hormone during menopause – which typically occurs around 52 years old – changes the wiring of the brain, potentially increasing the risk of cognitive decline and dementia later in life.
‘With decades of life remaining after menopause, it is important to understand the neurological effects of hormone changes at midlife,’ said Dr Abigail Testo, a researcher at the University of Vermont and the study’s lead author.
The research team at the Clinical Neuroscience Research Unit examined brain function across three menopausal stages: premenopause, perimenopause and postmenopause.
Rather than looking at how women perform tasks, the scientists measured brain activity during a resting state, the quiet moments when the mind is idling. They found that brain activity differed significantly across each stage.
While estrogen is best known for its role in sexual and reproductive development, it is also a key hormone that supports brain health by regulating energy use, protecting neurons and maintaining connections between brain cells.
When estrogen levels drop during menopause, which causes hot flashes, mood swings and night sweats, among other symptoms, the brain loses this support.
These changes can cause memory lapses in the short term and may increase dementia risk later on.
For decades, menopause was considered only a reproductive change. But neuroscientists now see it as a critical neurological transition, where falling estrogen levels may reshape the brain (stock)
‘Our research contributes to the growing body of work examining the relationship between menopause and the brain,’ Testo said.
Approximately 6,000 women enter menopause each day in the US — roughly 1.3 million annually, according to the NIH.
And women make up nearly two-thirds of all Alzheimer’s patients, prompting researchers to long wonder why.
This latest research, published in the journal Menopause, offers a clue.
Researchers analyzed brain scan data from the Human Connectome Project—Aging, a large-scale research effort. They focused on 151 women aged 40 to 55.
The women were divided into three groups based on their stage of menopause: premenopausal and still having regular periods, perimenopausal and experiencing irregular periods and postmenopausal with no periods for at least one year.
Using MRI brain scans, the scientists measured ‘resting-state functional connectivity’ to see how different brain regions communicate with one another when a person is simply resting, not performing any task.
They then compared these brain connectivity patterns across the three stages of menopause.
This brain scan shows a connection (red line) between the supramarginal gyrus (gray, involved in memory) and the planum temporale (blue, involved in language). Researchers found that the strength of this connection varied significantly across pre-, peri- and postmenopausal women
The researchers did not measure estrogen directly in the women they scanned. They used the clinical staging system, classifying women as pre-, peri-, or postmenopausal based on menstrual cycle patterns and time since last period.
They then inferred that estrogen levels differed between these stages because decades of research have firmly established that estrogen drops sharply as women transition from pre- to post-menopause.
Brain scans revealed clear differences in how brain regions communicate depending on a woman’s menopause stage.
One specific connection between the supramarginal gyrus and the planum temporale changed significantly across pre-, peri-, and postmenopausal women.
Postmenopausal women had weaker connectivity within this network than premenopausal women.
The supramarginal gyrus is a hub for memory and language. It gives the brain the ability to hold small bits of information in mind, such as a phone number or spoken directions.
The planum temporale, located just behind the ear, processes sound and supports language comprehension, including speech understanding.
The perimenopausal group did not show significant differences in connectivity compared with either the pre- or postmenopausal group.
This brain scan shows network differences between premenopausal and postmenopausal women. The highlighted areas had significantly lower connectivity in the postmenopausal group
The researchers suggested this may be because perimenopause is a transitional phase when the brain is shifting from its premenopausal to postmenopausal state, so its connectivity patterns may not yet be distinctly different from either end of the spectrum.
The changes in resting-state brain activity may represent an early neurological turning point with lifelong consequences for cognitive health.
Estrogen receptors are densely packed in regions critical for memory and learning, including the hippocampus and prefrontal cortex.
When estrogen binds to these receptors, it boosts glucose metabolism, the brain’s primary fuel, and encourages the growth of the tiny gaps where neurons pass messages called synapses.
Estrogen also protects neurons from inflammation and oxidative stress, essentially acting as a built-in brain maintenance system.
During menopause, ovarian production of estrogen declines by 80 percent or more. The brain, suddenly deprived of this support, undergoes measurable changes.
This research is among the first to document these changes using resting-state brain activity. The UVM team is continuing to investigate how hormonal changes influence brain aging beyond menopause.
Ongoing studies are exploring how both naturally occurring hormones and external hormone therapies may differently affect brain health in aging women.
Women with hearing loss scored about 1.2 points lower on cognitive tests than women without hearing loss, while men with hearing loss scored only 0.65 points lower
Diabetes lowered cognitive scores by 1.7 points in women but less than 0.6 points in men. The condition hit women’s cognition nearly three times harder than men’s
‘This is not just about reproduction,’ Dumas said. ‘It is about understanding the female brain across the entire lifespan.’
In a separate study, published in the journal Biology of Sex Differences, researchers from the University of California, San Diego, analyzed data from more than 17,000 older adults and found that women have more dementia risk factors than men and those factors harm women’s brain health more severely.
The results showed that women had a higher rate of seven of 13 well-known dementia risk factors, including depression, physical inactivity, smoking, poor vision, poor sleep, high cholesterol and fewer years of education.
Men, on the other hand, only had higher rates of three risk factors: hearing loss, diabetes and excessive alcohol use.
Four factors, including hearing loss, diabetes, high blood pressure and obesity, had a significantly worse impact on women’s cognitive performance than on men’s.
For instance, women with diabetes or hearing loss experienced larger drops in memory and thinking scores compared to men with the same conditions.
The researchers emphasized that many of these risk factors are modifiable, meaning they can be treated or managed.
They suggested women pay particular attention to addressing hearing loss, sleep problems, high blood pressure, diabetes and excess weight, especially during midlife and early older adulthood.
Treating these issues early could help lower the risk of dementia, which already affects seven million Americans, later in life.
