Alzheimer’s disease affects millions of people around the world, but women seem to carry a larger burden. In fact, nearly two-thirds of all Alzheimer’s cases are found in women. While it’s true that women tend to live longer than men – and age is the greatest risk factor for Alzheimer’s – researchers now believe that’s not the whole story.
Recent studies have revealed a much more complex picture involving brain biology, hormones, genetics, and even social and cultural experiences. One key moment in a woman’s life – menopause – might be a critical piece of the puzzle.
Dr. Roberta Brinton, a neuroscientist at the University of Arizona, has spent over three decades researching why women are more vulnerable to Alzheimer’s. Her interest in the subject began when she met a woman named Dr. Rowena Ansbacher, a clinical trial participant with early Alzheimer’s. After a heartfelt conversation, Brinton witnessed the sharp impact of memory loss when Ansbacher no longer recognized her moments later. That experience motivated Brinton to focus her career on understanding the female brain’s unique vulnerability to cognitive decline.
The Menopause Connection
As women reach midlife, they begin to experience menopause – a natural process that marks the end of menstrual cycles and a significant drop in estrogen levels. While estrogen is best known for its role in reproduction, it also plays a major part in how the brain functions. Estrogen helps brain cells use glucose for energy, supporting memory, attention, and overall cognitive function.
When estrogen levels fall, the brain struggles to get the energy it needs. Dr. Brinton’s research shows that in response, brain cells may start using alternate energy sources – including the brain’s own white matter, a fatty tissue that supports communication between brain cells. This “self-cannibalization” process can damage brain structures and potentially raise the risk of Alzheimer’s.
Brain Imaging Reveals More
Dr. Lisa Mosconi, a neuroscientist at Weill Cornell Medical College, has used brain scans to compare men’s and women’s brains during midlife. Her research shows that women between ages 40 and 65 have:
- 22% less brain glucose metabolism (less energy available for brain activity)
- 11% less white matter
- 30% more Alzheimer’s-related plaques compared to men the same age
Mosconi emphasizes that Alzheimer’s doesn’t suddenly appear in old age – it likely begins decades earlier, around the same time many women enter menopause. These early changes may go unnoticed but could signal increased risk later in life.
Not Every Woman Develops Alzheimer’s – So What Else Plays a Role?
While every woman goes through menopause, not all develop Alzheimer’s. Researchers believe that a mix of genetic, hormonal, and lifestyle factors shape a woman’s risk.
For example, women with metabolic syndrome – marked by high blood sugar, high triglycerides, or blood pressure problems – are more likely to develop Alzheimer’s after menopause. Risk is even higher for women who carry a specific gene called APOE4, which is strongly linked to Alzheimer’s.
Fortunately, midlife may offer a window of opportunity to lower that risk. By managing conditions like high blood pressure and metabolic syndrome during menopause, women may be able to support long-term brain health.
The Role of Hormone Therapy in Brain Health
One potential strategy for supporting women’s brain health during menopause is hormone replacement therapy (HRT), which restores estrogen levels. In a large review study, Dr. Brinton found:
- Women using HRT for 1–3 years had a 40% lower risk of developing Alzheimer’s or Parkinson’s.
- Women using HRT for 3–6 years saw a 60% risk reduction.
- Women on HRT for more than 6 years experienced an 80% lower risk.
These findings are promising, but HRT is not without controversy. Some studies suggest it could increase dementia risk, particularly if started later in life. Timing may be everything: starting HRT during menopause might protect the brain, while starting it years later may not offer the same benefits – or could even be harmful.
Experts, including Dr. Michelle Mielke from Wake Forest University, agree that HRT can be safe for short-term use to relieve menopausal symptoms. However, they caution that it shouldn’t be used solely to prevent Alzheimer’s, especially without discussing individual risk factors with a physician.
Estrogen Exposure Over a Lifetime Matters
Estrogen’s protective effects seem to depend not only on menopause but also on how long a woman is exposed to the hormone throughout her life. A 2020 study of 15,000 women found:
- Women with shorter reproductive spans (less than 34 years between first period and menopause) had a 20% higher risk of dementia.
- Women who started menstruating at 16 or older had a 31% higher Alzheimer’s risk than those who started around age 13.
- Women who had their ovaries and uterus removed had an even higher risk.
Interestingly, the study also found that women with three or more children had a 12% lower Alzheimer’s risk, possibly due to social support and caregiving benefits that come with having a larger family.
Social and Cultural Factors: Beyond Biology
While hormones and genetics matter, social and cultural experiences also shape brain health. Around the world, Alzheimer’s rates in women vary by country. In some places, such as England and Australia, dementia has become the leading cause of death for women. These patterns may reflect not just biology, but life history – including war, famine, education access, and societal gender roles.
For example, in post-World War II Europe, older women often faced severe stress, limited education, and fewer job opportunities. These early-life disadvantages can affect cognitive function decades later.
Women with higher education levels tend to have better “cognitive reserve” – the brain’s ability to compensate for damage. Research shows that women who work in mentally demanding jobs experience slower memory decline as they age. Yet, historically, many women were denied equal access to education and career advancement, reducing their opportunity to build this cognitive reserve.
The Role of Structural Sexism
Newer research is also uncovering how societal-level discrimination – known as structural sexism – affects brain health. A study led by Justina Avila-Rieger at Columbia University analyzed 21,000 women and compared their memory performance to the level of sexism in the state where they were born. Women who grew up in states with higher levels of sexism – such as fewer women in leadership, larger wage gaps, and less workplace equality – experienced faster memory decline after age 65.
Black women were disproportionately affected, suggesting that discrimination based on both gender and race takes a heavier toll on brain health. The stress of lifelong inequality can lead to chronic inflammation, which may damage brain cells and increase dementia risk over time.
“We tend to focus on biology,” Avila-Rieger says, “but changing the social environment may have an even bigger impact on women’s health.”
A Call for Better Research
Historically, women have been underrepresented in medical research – even though they are more likely to get Alzheimer’s. Until recently, most dementia studies were not designed to explore sex differences, and many clinical trials still don’t include enough female participants. As a result, many Alzheimer’s symptoms in women may go undiagnosed or misinterpreted.
For example, women tend to perform better on common memory tests, which can mask early signs of cognitive decline. When they do report symptoms, doctors may dismiss them as stress, anxiety, or depression.
Meanwhile, research funding also falls short. In 2019, just 12% of NIH Alzheimer’s research funding went to women-focused projects. A nonprofit analysis found that doubling investment in female-focused dementia research would ultimately save nearly $1 billion by reducing healthcare costs and time spent in nursing homes.
Moving Toward a More Inclusive Approach
Experts say we need a broader approach to understanding and preventing Alzheimer’s in women. That means:
- Supporting hormone balance during midlife through healthy lifestyle choices- and, in some cases, HRT under medical supervision
- Managing chronic health conditions like high blood pressure, diabetes, and metabolic syndrome
- Reducing gender-based stressors and addressing structural inequalities
- Increasing women’s access to education and cognitively stimulating careers
- Prioritizing research that includes sex and gender differences
Dr. Mosconi, who now leads a $50 million global program focused on Alzheimer’s in women, believes we’re just scratching the surface. “We owe women centuries of research,” she says.
A New Chapter in Alzheimer’s Prevention
Alzheimer’s disease is not simply a disease of old age – it may begin years, even decades, before symptoms appear. For women, especially, the transition into menopause could be an important turning point. By paying attention to hormonal health, lifestyle risks, and the effects of social and cultural inequality, we may be able to change the course of Alzheimer’s and improve outcomes for future generations of women.
Source: Moutinho, S. Women twice as likely to develop Alzheimer’s disease as men — but scientists do not know why. Nat Med 31, 704–707 (2025). https://doi.org/10.1038/s41591-025-03564-3
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