Earlier menopause is linked to faster memory decline and earlier Alzheimer’s onset

New research suggests that women who experience menopause at an earlier age tend to have faster rates of memory decline and a higher risk of developing Alzheimer’s disease later in life. The research, published in JAMA Network Open, also provides evidence that an earlier transition into menopause is linked to accelerated structural changes in the brain decades later. These findings indicate that the age a woman stops menstruating might serve as an early indicator of her long-term neurological health.

Menopause marks a major biological transition when a woman stops menstruating and her ovaries cease producing hormones like estrogen on a regular cycle. This loss of estrogen is thought to affect brain health, as the hormone helps support brain cell function, maintain healthy blood vessels, and protect against inflammation. Alzheimer’s disease is a progressive brain disorder that slowly destroys memory and thinking skills. Women have a higher lifetime risk of Alzheimer’s disease than men, even after accounting for the fact that women tend to live longer.

A 2014 study found that women who had their ovaries surgically removed at younger ages experienced faster cognitive decline and more Alzheimer’s-related brain changes later in life. Building on that idea, a 2012 study demonstrated that surgically removing one or both ovaries is linked to a progressively higher risk of developing dementia. These functional risks are mirrored by physical changes in the brain, as a 2023 review compiled brain scan studies showing that menopause is associated with measurable shrinkage in areas of the brain critical for memory and thinking.

This aligns with research covered by PsyPost earlier this year, which indicated that post-menopausal women exhibit reduced gray matter volume, the brain tissue made up largely of neuronal cell bodies and synapses that handles information processing, in key brain regions compared to pre-menopausal women.

To expand on this foundation, a research team led by Riley Bove, a professor of clinical neurology at the UCSF MS and Neuroinflammation Center, set out to track long-term rates of brain shrinkage and Alzheimer’s disease progression across both natural and surgical menopause. They wanted to see if the age at which a woman undergoes this transition affects the physical structure of her brain decades later.

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The study’s origins were deeply personal for the researchers. “My grandmother experienced adversity over her lifespan, as well as early surgical menopause,” Bove, who also directs the Bove Lab at the UCSF Weill Institute for Neurosciences, told PsyPost. “She developed Alzheimer’s Disease when I was in high school. Watching her brain and self change, I always wondered about the effect of her reproductive experiences on her brain health.”

To explore these questions, the researchers analyzed data from 2,603 older women participating in two long-running projects: the Religious Orders Study and the Rush Memory and Aging Project. The women had an average age of 78 when they enrolled and did not have known dementia at the time. Researchers tracked the participants for up to 18 years, assessing them annually with a battery of cognitive tests that measured skills like memory and thinking speed.

The team also collected self-reported information on reproductive history, such as the age at which the women began menstruating and the age they stopped. This allowed the authors to calculate each participant’s reproductive lifespan, which is the total number of years between a woman’s first period and her final period. The women were also asked whether their menopause was natural or surgical.

Beyond cognitive testing, the study involved brain autopsies for 1,287 women who passed away during the research period, allowing pathologists to look for physical signs of Alzheimer’s disease. A subgroup of 774 women underwent brain scans using magnetic resonance imaging (MRI) every two years. These scans allowed the researchers to measure changes in total brain volume and to track the accumulation of white matter hyperintensities. White matter hyperintensities are areas of the brain that appear as bright spots on an MRI scan, signaling damage or injury to the brain’s white matter, which acts as the communication network between different brain regions.

The findings indicate that an earlier age at menopause is associated with a faster decline in general cognitive abilities, as well as a more rapid decline in episodic memory, which is the ability to remember specific past events. Women who experienced menopause earlier were also diagnosed with Alzheimer’s disease at an earlier age. For example, the models estimated that a woman who went through menopause ten years earlier than another woman might experience nearly two fewer years free of Alzheimer’s disease in her old age.

When the researchers separated the data by menopause type, they found that the risks of cognitive decline and earlier Alzheimer’s diagnosis were stronger in women who experienced surgical menopause. Surgical menopause involves the removal of the ovaries, leading to a sudden, dramatic drop in hormone levels, unlike the gradual decline seen in natural menopause.

“We found that over time, those who had experienced earlier menopause had steeper patterns of cognitive change, earlier onset of Alzheimer’s, and more injury in the white matter of their brains, than women whose menopause occurred later,” Bove explained. “This suggests that longer exposure to reproductive hormones during the reproductive years (i.e., a later age at menopause) could play a role in maintaining brain health long-term.”

The researchers were particularly surprised to detect this association between menopause and brain health so long, often several decades, after the women’s final menstrual periods.

However, the brain scan data told a slightly different story regarding physical brain structures. While earlier menopause had only a modest link to total brain volume loss overall, it was strongly associated with vascular damage in women who went through natural menopause. Specifically, women who experienced natural menopause at an earlier age showed a much faster accumulation of white matter hyperintensities. The researchers calculated that a woman who underwent natural menopause just five years earlier than an otherwise identical peer would accumulate roughly 15 percent more of this white matter damage over a decade. This specific physical change was not observed in the surgical menopause group.

Maria Pia Campagna, a Chancellor’s Postdoctoral Fellow in neurology at UCSF and the study’s lead author, noted that these findings represent averages across a large group of women, not predictions for any one person. “The difference in overall brain volume was small enough that it fell below what we would usually call a small effect,” Campagna said. However, she pointed to the multi-year transitional phase leading up to menopause when hormone levels begin to fluctuate, known as the perimenopausal period. “The larger white matter finding is, as Dr Bove has said, an opportunity for intervention during the perimenopausal period as it reflects the health of small blood vessels, which is among the more modifiable contributors to brain aging,” Campagna said.

The study also evaluated reproductive lifespan as a secondary measure of long-term hormone exposure. Consistent with the main results, women with a shorter reproductive lifespan tended to experience faster cognitive decline and an earlier onset of Alzheimer’s disease. The findings are in line with research covered by PsyPost earlier this year, which found that greater lifetime estrogen exposure is generally associated with better cognitive performance and a reduced risk of dementia.

As with all research, there are some caveats to consider. The study relies on observational data, meaning it provides evidence for a link between menopause timing and brain aging, but it cannot confirm that early menopause directly causes these negative outcomes. It is possible that early natural menopause is simply a marker of a broader, accelerated aging process within the body, which also affects the brain. The researchers noted that the stronger cognitive findings in the surgical menopause group lend some support to a direct hormonal role, since surgery abruptly cuts off hormones regardless of the body’s natural aging timeline.

“One major unanswered question is whether menopausal hormone therapy is protective against brain aging,” Bove pointed out. While observational studies suggest it might be protective, she noted that healthier women might simply be more likely to start the medication. “The higher quality interventional trials, which can reduce the biases that we see in observational studies, have not shown that it is, but perhaps women have not yet been followed for long enough.”

Another detail to keep in mind is that the study relied on participants recalling the ages at which they experienced their first and last menstrual periods. While generally reliable, human memory is not perfect, and small errors in recall could affect the data. The researchers also did not have complete information on other factors that affect a woman’s lifetime hormone exposure, such as pregnancies, breastfeeding, or the use of oral contraceptives.

Above all, the researchers want their findings to encourage proactive health management. “This study is not intended to alarm women. A majority of women go through menopause and maintain brain health over their postmenopausal lifespan,” Bove said. “Rather than alarming women, we’d like to empower women to consider the perimenopause as a window of opportunity. An opportunity to assess carefully their risk factors for brain aging and to personalize the care and interventions (such as sleep study, mood management, exercise program, blood pressure treatment) intended to support brain longevity.”

Looking forward, Bove said the team hopes “to see more focused scientific exploration into mechanisms, as well as more concrete implementation of what we already know into clinical practice.” She noted that her colleague Aleksandra Pikula is actively pursuing this implementation work. The research also fits into a broader roadmap the researchers recently published that “calls for more focused research and care around menopause and brain health,” Bove added. “Several pioneering scientists and groups have been calling for sustained attention to this question for decades,” she noted. “It’s great to see that the public, and science, are finally catching up.”

The study, “Age at Menopause and Brain Atrophy Among Older Women,” was authored by M. Pia Campagna, Julie A. Schneider, Lisa L. Barnes, Konstantinos Arfanakis, Galit Levi Dunietz, David A. Bennett, and Riley M. Bove.