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Two missing words tipped off Heidi Long that her mother might have dementia. Nearly a decade ago, in the springtime, Long was expecting a call from her mom. When the call never came, she decided to give her mom a ring instead. After about 10 minutes of casual conversation about the weather and politics, Long knew there was a problem.
“My mom always remembered important dates,” says Long, a dental hygienist who lives in Kauai, Hawaii. “But I turned 25 that day, and my mom didn’t remember to wish me—her only child—a happy birthday.”
Before they hung up, Long mentioned that she was going out with friends for her birthday. Her mother awkwardly tried to cover up the fact that she’d forgotten the day.
Long couldn’t let go of the conversation, though, and started recalling other strange behaviors her 49-year-old mother exhibited. On one occasion a few years earlier, it had taken her mom three tries to leave the house for work because she kept forgetting her purse. Each time, she’d come back to the house, pick up something else, and leave—sans purse. Long had thought at the time that her mother just had a lot on her mind. On another occasion, when her mom made her famous twice-baked-potatoes recipe—a family favorite—it was clear that something was off. It turned out that, for the first time ever, she’d forgotten some essential ingredients. The potatoes were also surprisingly overcooked.
A few months after the birthday incident, on a walk with her mother, Long found herself answering the same question three times in a row. “So, what are you going to do tonight?” her mother asked every time they rounded a corner. “I stayed calm on the walk,” says Long. “But when we got back to the house, I sat my parents down and said, ‘We need to talk.’ ”
More than 6 million Americans over the age of 65 have Alzheimer’s, a broad term that describes losing so much of your memory, problem-solving, and language skills that it interferes with your day-to-day life. Alzheimer’s is the most common form of dementia, followed by other types such as Lewy body dementia, frontotemporal dementia, vascular dementia, and more.
By 2060, new dementia cases are expected to more than double in the U.S., reaching approximately 1 million new diagnoses per year, per recent research.
What Long and her family didn’t know at the time was that women are almost twice as likely to develop Alzheimer’s, and that you don’t need to be a senior citizen to be at risk. Early-onset cases can be diagnosed as early as 30, and though they’re rare (occurring in only about 5 percent of people with Alzheimer’s), they do happen. Together, these two facts made Long’s mom’s shocking Alzheimer’s diagnosis make more sense.
The Gender Divide In Our Minds
Despite the fact that nearly two in three Alzheimer’s patients are female, only 12 percent of Alzheimer’s research was centered on women as of 2019, leaving the medical community with a dearth of information about the very population hit hardest by the disease.
“It’s a little bizarre that we haven’t focused on women first and foremost,” says Fanny Elahi, MD, PhD, associate professor of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City. “In research, we always focus on studying the highest risk group for every disease. All the epidemiological and demographic data shows us that white men are not the highest risk group. It’s women. It’s time we do a 180.”
For decades, the gender discrepancy in Alzheimer’s disease incidence has been explained, at least in part, by the fact that women live longer than men do. (Data from 2022 shows there’s a nearly six-year gap between the genders’ life expectancy, with the average woman living to 80.2 years and the average man living to 74.8 years.) As you age, your risk of developing the disease increases. About one in three people over 85 have Alzheimer’s compared with about one in nine people over 65. But now, experts aren’t so sure that longevity is the only reason for different diagnosis rates. Studies have shown that even when looking at a cohort of men and women in the same age range, women are still more likely to be diagnosed with Alzheimer’s.
Women also respond very differently to the disease than men do. For example, women tend to have more abnormal accumulations of an Alzheimer’s-related protein in their brains before actually reaching the point of cognitive decline (in doctor-speak, this is called being more “resilient” to the disease progression). This could be because women’s brains tend to have a larger “reserve” when it comes to verbal material (like stories, words, things we’ve heard about), experts say, so it takes longer for them to lose this. They also have better “social brain function,” per Dr. Elahi, meaning that women tend to maintain more social connections and participate in more social activities. Some research suggests that social isolation may increase your risk for Alzheimer’s, while connection may increase resilience. “The more connections you have to your memories, the easier it is to retrieve those memories,” Dr. Elahi says.
Men appear to have a more “linear relationship” with Alzheimer’s compared to women, slowly losing memory and verbal abilities as the disease progresses, says Sarah Banks, PhD, a neuropsychologist at UC San Diego Health and director of neuropsychology at the multidisciplinary UC San Diego Health Center for Brain Health & Memory Disorders. “With women, it’s more like falling off a cliff,” she says. “Women do okay, do okay, and do okay until a certain amount of pathology has built up, and then there’s a more rapid decline after that.”
Long saw this firsthand. Her mother’s health hit this “cliff” and went downhill very quickly after being diagnosed, suggesting she’d been struggling with the disease for a long time before her family took notice. Within two years, she had problems communicating effectively.
Experts are still working to figure out what exactly pushes women off this edge so fast. And understanding the unique way this disease operates in women’s brains—the role of hormones, how women stay resilient for so long, and why they’re more likely to develop Alzheimer’s in the first place—could go a long way toward helping scientists and doctors unlock some big answers about the disease itself.
“I see women’s brain health as a window into what might be really important to focus on so that we can get effective treatments for Alzheimer’s disease,” says Banks.
A Primer On Plaque
In 1901, a German psychiatrist named Alois Alzheimer met a woman at a Frankfurt psychiatric hospital who fascinated him. She was middle-aged, like Long’s mother, but had severe memory loss, confusion, and aggression. He followed the progression of her illness until she passed away five years later. After her death, Alzheimer examined her brain—and found two abnormalities that remain the key markers associated with the degenerative brain disease that is named after him: protein deposits and tangled nerve fibers.
Today, doctors know the “protein deposits” Dr. Alzheimer found in his patient were a toxic beta-amyloid, a protein that clumps together to form plaques between nerve cells. Some amyloid proteins can be beneficial in bolstering your immune system to help fight disease, but too much buildup can disrupt your brain’s ability to function and eventually lead to Alzheimer’s. Women tend to produce more amyloid plaques than men, which experts think may be an evolutionary advantage that developed to promote stronger immune systems to protect their babies. But as women age, that amyloid puts them in danger. Some existing Alzheimer’s medications—and new ones in development—aim to clear that beta-amyloid plaque from the brain.
“I see women’s brain health as a window into what might be really important to focus on so that we can get effective treatments for Alzheimer’s disease,” says Banks.
The tangled nerve fibers Dr. Alzheimer found are now known to be a result of accumulations in cells of a protein called tau. In people with Alzheimer’s, chemical changes in this protein cause it to behave abnormally, increasing the number of tau and forming tangled structures. These tangles are “a strong marker of diseased cells,” says Dr. Elahi.
When tau proteins are damaged, unnecessary, or old, they are chemically “tagged” for recycling in the cell. Interestingly, women have a higher concentration of an enzyme that removes these essential “tags,” meaning the cell doesn’t get this important message to recycle the tau, and the proteins build up, clump, and twist together. This bigger enzyme concentration is possibly due to the fact that the gene coding for the enzyme is found on the X chromosome. Researchers wonder if having a Y chromosome might protect men from Alzheimer’s, while having two X’s might have the opposite effect for women.
Together, the cellular changes and development of “bad” proteins inside neurons causes interruptions in communication between brain cells, which then degenerate and die. “Think of it as a three-step process,” says Banks. “The cells get disrupted first, which leads to a breakdown in the functioning and size of the brain, which results in changes in thinking and behavior.”
The Hormone Question
Scientists know that estrogen affects almost every single cell in a woman’s brain, but they have only recently begun exploring the myriad impacts this has on our health and longevity.
Historically, the medical world hasn’t looked at hormones in relation to Alzheimer’s risk, says Banks. But it should. We know there are estrogen receptors in the brain, that estrogen is a protective hormone, and that women lose estrogen (along with cognitive functioning) during menopause, she explains. So it stands to reason that hormones could impact women’s brain health and Alzheimer’s risk. There’s even some evidence that testosterone could have a protective effect in men’s brains—and could potentially help women, too (but more studies are needed). In fact, Banks’s research found that higher testosterone levels in women could be protective for their brain health.
In one study, women with lower testosterone levels who had the APOE4 gene variant (a gene tied to increased Alzheimer’s risk) had worse global cognition, processing speed, and verbal memory than others in the study. It may be that, with more data, low testosterone could one day be considered a modifiable risk factor for Alzheimer’s in women. But more research is needed to better understand this connection, says Banks.
Perhaps most important, experts say they need a better understanding of the extent and ways in which menopause—which famously involves massive hormonal changes in women as estrogen and progesterone fluctuate—affects brain health. “What reproductive changes are telling us about later risk for Alzheimer’s disease is the focus of a lot of research that’s going on now,” says Jill M. Goldstein, PhD, MPH, professor of psychiatry and medicine at Harvard Medical School and founder and executive director of the Innovation Center on Sex Differences in Medicine at Massachusetts General Hospital.
Research shouldn’t look only at the start and end of menopause itself, though. Alzheimer’s actually begins to develop in the brain up to 15 years before outward signs appear, so studies should ideally examine the entire spectrum of hormonal fluctuations in a woman’s body, as well as psychological and social changes. “We need to map perimenopause to two decades after menopause,” says Dr. Elahi. “That’s where the risk is building up.”
How Stress Comes Into Play
Another key factor in cognitive decline is stress, because it impacts some of the same brain regions and physiology (such as hormonal and immune factors) that regulate memory and memory function, per Goldstein. It also results in higher levels of cortisol, which isn’t good for brain health.
But men and women have different biological, psychological, and social stress experiences. For example, some research suggests women may internalize stress more while men can more easily separate themselves from it. What’s more, women routinely reported feeling more stressed than men in 2023, and tend to be the caregivers for children, partners, and parents (not to mention that women represent more than 60 percent of Alzheimer’s and dementia caregivers).
What’s more, researchers found that stress increases Alzheimer’s risk in female mice’s brains, but not in males’. More studies are needed to understand how this might play out in humans, but these preliminary findings seem to follow what we already know about the impact of stress. “Stress response does differ by sex and can impact the aging brain when it is chronic over time,” says Goldstein.
Where The Science Needs To Go
Thankfully, there’s been a slow but steady surge in interest and research funding for women and Alzheimer’s over the past few years.
In 2016, the National Institutes of Health announced that it expected applicants for funding to factor sex into their research. In 2020, the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic became the nation’s first and only Alzheimer’s disease prevention center for women, funding research into big questions surrounding sex hormones’ impact on Alzheimer’s, the gut microbiome’s role in disease progression, and why women build up more tau tangles in their brain than men.
Dr. Elahi, for her part, is passionate about the research she’s doing on molecules that regulate women’s vascular systems, hoping that findings could lead to new treatments to prevent declining brain function. Meanwhile, Banks has been studying the relationship between hormones and inflammation in the brain by measuring levels of cerebrospinal fluid (which surrounds the brain and spinal cord) to learn how these variables may affect women’s risk for the disease.
“Stress response does differ by sex and can impact the aging brain when it is chronic over time,” says Goldstein.
“When a factor such as sex is a big risk factor, if you don’t go after studying it, you are turning away from one of the biggest clues of vulnerability,” says Dr. Elahi. “Solving the mystery behind women’s risk, for all diversities, also helps men because we’re going to be able to better understand the fundamental principles of it.”
Two years ago, the Biden Administration created the White House Initiative on Women’s Health Research to improve prevention, diagnosis, and treatment of conditions that affect women disproportionately. This initiative included nearly $1 billion in research funding—including money for researching Alzheimer’s in women—but its future is unclear under the Trump administration. (The website currently pops up with a message saying “Page Not Found.”)
While more research data is certainly a boon, and it makes sense to focus studies on women, experts say they don’t expect a better understanding of women’s brains to completely unlock the mysteries of this complex disease. “There are thousands of things we can measure for and so many factors for risk,” says Dr. Elahi. And with no singular cause for the disease, we can’t expect a singular treatment to work.
For example, people with the APOE4 gene variant and high cholesterol will probably need different treatment from those with sleep apnea and a different genetic risk factor, says Banks. “So the question is, how do we create precision [medication] cocktails for people?”
For now, as doctors ask for more research dollars, loved ones are left dealing with a devastating, debilitating disease and few answers.
Back in Virginia Beach, where Long was living at the time, her family began researching her mother’s illness online, and her father and aunt stumbled across a website. It was the Brain Donor Project, a nonprofit partially supported by the National Institutes of Health that ensures brain tissue donated by people who die from Alzheimer’s becomes part of national (and often international) neuroscience research efforts. By the time she passed, Long’s mother was signed up to donate her brain.
“We wanted to do whatever we could to make sure another family wouldn’t go through what we did,” says Long, who adds that the brain donation post-mortem report found her mother had Lewy body disease, another dementia-related progressive brain disease, in addition to Alzheimer’s. “My mom worked in a nursing home. I think she knew something was wrong for a while but didn’t want to tell anyone. I think she also would’ve wanted to help cure this disease in any way she could. And she is.”
Practicing Prevention
“We used to think that Alzheimer’s was inevitable,” says Banks. “Now we know that even if you’re at risk, up to 45 percent of that risk can be reduced.” Here’s what experts recommend.
1/ Find A Workout You Love
One of the easiest ways to boost brain health is to get moving. “Physical exercise is the low-hanging fruit of prevention,” says Banks. “It’s also the most robust, so it’s really important in terms of staving off cognitive decline.” It’s also powerful at rebuilding your brain. “Physical activity can increase nerve growth and neurogenesis,” adds Goldstein.
2/ Talk To Your Doc About Hormone Replacement
Some research shows that estrogen therapy for women hitting menopause can help protect a woman’s brain from Alzheimer’s. “The Women’s Health Initiative had a significant negative impact on taking hormones back in 2002, suggesting, among other things, that they were associated with dementia risk,” says Goldstein, referencing the report that stymied hormone therapy prescriptions by suggesting they increased the risk of heart attacks, strokes, and breast cancer. “But when they reanalyzed the data, women who had hormone replacement during early postmenopause or late perimenopause saw a cognitive function benefit. This suggests there is a window of opportunity for asking your doctor if this is a good option for you.”
3/ Take Care Of Your Heart
Heart conditions like high cholesterol and hypertension can increase your risk of dementia but are also controllable. “What’s good for the heart is good for the brain—and that may be especially important for women,” says Banks.
4/ Get Quality Sleep
For women with sleep apnea, a stunning 90 percent go undiagnosed, according to the Society for Women’s Health Research. “While men tend to be loud snorers, women tend to wake up with a headache or not feeling refreshed,” says Banks. “But it’s modifiable and treatable.” In addition to depriving your brain of oxygen, sleep apnea is also often accompanied by cardiovascular diseases like hypertension that can increase your risk of dementia. Experts are still trying to figure out why this is the case, but on the whole, they suggest finding ways to improve your time under the covers.
5/ Stay Social
Regardless of age or sex, loneliness can increase your risk of dementia, research shows. Taking steps to avoid isolation and dissatisfaction with your relationships can be socially and physically beneficial.
6/ Check Your Family Tree
Having a first-degree relative with Alzheimer’s slightly increases your risk, and having more than one may signal an even more increased risk. “If a person has risk factors in their family, they may want to engage in personal lifestyle habits that have a positive impact on helping to maintain intact memory function,” says Goldstein. These habits can include a healthy diet, getting enough exercise and sleep, and doing activities that keep your mind active. “If you can intervene early, you may be able to stop the process down the road.”
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