Why are women more likely to develop Alzheimer’s disease?
By Andrew E. Budson, MD, Contributor; Editorial Advisory Board Member, Harvard Health Publishing
Did you know that of the 6.2 million people with Alzheimer’s disease who are 65 or older in this country, almost two-thirds are women? This means that Alzheimer’s disease is almost twice as common in women compared to men. Why is Alzheimer’s disease more common in women?
Women live longer
The first and most important reason is that women tend to live longer than men. If you look at actuarial life tables, you can see that a baby girl born in 2019 is likely to live five years longer than a baby boy: 81 versus 76 years.
The greatest risk factor for Alzheimer’s disease is age: the older you are, the more likely you are to develop Alzheimer’s disease. For example, out of 1,000 people, the incidence (the number who develop Alzheimer’s each year) depends on age:
- 4 out of 1,000 people ages 65 to 74 develop Alzheimer’s each year
- 32 out of 1,000 people ages 75 to 84 develop Alzheimer’s each year
- 76 out of 1,000 people ages 85 and older develop Alzheimer’s each year.
So, one reason that there are more women with Alzheimer’s disease than men is simply that there are more older women than older men living in our society — 5.7 million more of them — and the older you are, the more likely you are to develop Alzheimer’s disease. But that’s not the whole answer.
The incidence of Alzheimer’s is greater in women
Your chances of developing Alzheimer’s disease late in life are somewhat greater if you are a woman than a man. One study followed 16,926 people in Sweden and found that, beginning around age 80, women were more likely to be diagnosed with Alzheimer’s disease than men of the same age. Similarly, a study based in Taiwan found that one’s chances of developing Alzheimer’s disease over seven years was greater in women compared to men. And a meta-analysis examining the incidence of Alzheimer’s disease in Europe found that approximately 13 women out of 1,000 developed Alzheimer’s each year, compared to only seven men.
So, women living longer than men cannot be the whole answer as to why women are more likely than men to develop Alzheimer’s disease, because even among individuals who are living and the same age, women are more likely to be diagnosed with Alzheimer’s than men.
The incidence of non-Alzheimer’s dementia is not greater in women
One clue to the answer to this puzzle is that your chances of developing dementia from a cause other than Alzheimer’s disease is not greater if you are a woman. For example, the study examining dementia rates in Sweden found that both women and men were equally likely to develop a non-Alzheimer’s dementia as they aged. That rates of Alzheimer’s disease differ by gender, whereas rates of non-Alzheimer’s dementias do not, suggests that there must be a specific interaction between Alzheimer’s disease and gender.
Amyloid deposition in Alzheimer’s may be fighting infections
Another clue to this puzzle comes from the work of Harvard researchers, who have suggested that amyloid, one component of Alzheimer’s disease pathology, may be deposited in order to fight off infections in the brain. If their suggestion turns out to be correct, we might think of Alzheimer’s disease as a byproduct of our brain’s immune system.
Autoimmune disorders are more common in women
The last piece of the puzzle is that women are about twice as likely to have an autoimmune disease compared to men. The reason for this difference is not entirely clear, but it is clear that the immune system is generally stronger in women than men, and many autoimmune diseases are more common during pregnancy. It may be that women’s stronger immune system developed through evolution to protect the fetus from infections. So, as part of their stronger immune systems, women may end up having more amyloid plaques than men.
Putting the pieces together
By combining all of this information, one possible explanation as to why women’s risk of Alzheimer’s disease is greater than men’s — in addition to women living longer — is:
- The amyloid plaques that cause Alzheimer’s disease may be part of the brain’s immune system to fight against infections.
- Women have stronger immune systems than men.
- As part of their stronger immune systems, women may end up having more amyloid plaques than men.
- Because they may have more amyloid plaques than men, this theory may explain why women end up having a greater risk of developing Alzheimer’s disease.
Please note the italicized words “may” that was used. Although the ideas I have presented here are logical, coherent, and form the basis of a good theory, they have not yet been proven to be correct. More research is needed!
The Bottom line
You are more likely to develop Alzheimer’s disease over your lifetime if you are a woman, because women live longer than men and, possibly, because women have stronger immune systems compared to men.
Does that mean that if you’re a woman, you’re more likely to develop Alzheimer’s disease and there’s nothing you can do about it? Not at all! You can do many things to reduce your risk of Alzheimer’s today.
- Engage in aerobic exercise such as brisk walking, jogging, biking, swimming, or aerobic classes at least 30 minutes per day, five days per week.
- Eat a Mediterranean menu of foods including fish, olive oil, avocados, fruits, vegetables, nuts, beans, whole grains, and poultry. Eat other foods sparingly.
- Sleep well — and clean those Alzheimer’s plaques out of your brain.
- Participate in social activities and novel, cognitively stimulating activities.
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What Does Estrogen Do in the Brain? A Lot More Than You Might Realize.© Danii Pollehn/Adobe Stock
What Does Estrogen Do in the Brain?
A Lot More Than You Might Realize.
Story by Cassie Shortsleeve
Higher levels of estrogen can contribute to the development of breast cancer. Estrogen stimulates cell growth in the breast tissue, and prolonged exposure may increase the risk. Hormone receptor-positive breast cancers, which respond to estrogen, are common. Hormone therapy and medications that reduce estrogen’s effects can be part of breast cancer treatment to inhibit tumor growth fueled by estrogen.
Lack of estrogen and dementia – Search | American Heart Association+2
Progesterone and estrogen imbalances. Imbalances between estrogen and progesterone can lead to various health issues, including menstrual cycle disruptions, mood changes, hot flashes, infertility, and increased risk of certain cancers12. These hormones also play a role in metabolism and gastrointestinal function3. Search Videos
For decades, estrogen was discussed primarily as a “sex hormone.” After all, it does play a crucial role in reproductive health. Yet, starting in the 1980s, the conversation shifted when emerging science suggested estrogen positively impacts brain areas linked with memory. This is the message that Jill Daniel, Ph.D., professor of brain science and psychology at Tulane University, opens up most of her professional presentations with. “It was really exciting at the time to find out estrogens have these effects in brain areas other than the reproductive ones,” Dr. Daniel, who studies estrogen’s brain impacts.
Since the 80s, a large body of research has indicated that estrogen impacts everything from cognition to mood to a person’s risk of developing neurodegenerative diseases such as Alzheimer’s. “One of the hypotheses is that the loss of estrogens in middle age increases our vulnerability for diseases of brain aging; we lose this neuroprotective effect of estrogen,” says Dr. Daniel.
Of course, science around estrogen and menopause—a noteworthy time of estrogen loss—is largely lacking; research suggests that 99% of studies on the biology of aging leave menopausal subjects out. Needless to say, there’s a lot we don’t know, but there’s also a lot we do. Here’s a bit more about the ways estrogen impacts how we feel and think from those who study it—and tips for maintaining some stability during times of hormonal upheaval.
Estrogen impacts everything from learning, to memory, to mood.
Estrogen has a direct impact on cognition. Some of Dr. Daniel’s research on the hippocampus—a brain region key for learning and memory—has indicated that high estrogen levels are linked with increased connectivity throughout the brain. “There’s a pretty dramatic change when estrogen levels are high versus when they’re low.” Levels of neurotransmitters (brain chemicals important for memory) are also higher when estrogens are around, she says. So, it’s not surprising that the loss of estrogen can result in changes such as brain fog, Daniel says.
2/3 of Alzheimer’s Patients are Women, Here’s What it Does to the Brain – Search
The aspect of cognition that appears to be affected most by estrogen is verbal learning in memory—essentially, the ability to learn something new then recall it later. Studies indicate that menopausal women experience declines in these abilities. But it’s not just during times of low estrogen that you might notice changes; it’s also during times of fluctuating estrogen levels: the luteal stage of the menstrual cycle (after ovulation and before your period), pregnancy, postpartum, or during perimenopause, the transformation between your reproductive years and menopause where estrogen levels go through a rollercoaster of ups and downs before finally leveling off.
“Women’s brains don’t like changes in hormones,” Pauline Maki, PhD, director of Women’s Mental Health Research Program at the University of Illinois Chicago, tells SELF. Most conversations around the hormone are focused on estrogen withdrawal, but there are some women who are very sensitive to increases in estrogen, too, Dr. Maki says. “During perimenopause, you have both the increases in estrogen and withdrawal; it’s unpredictable.”
Variable estrogen levels impact mood, says Dr. Maki, who co-authored the first guidelines to identify and treat depression in perimenopause. She says that “elevated depressive symptoms” (where you may feel depressed but don’t meet a clinical definition of depression) “reliably increase in the perimenopause regardless of whether a woman has a history of depression.”
There’s also research that shows some women become depressed during the perimenopause transition for the first time, suggesting some of us might carry a “predisposing factor to getting depressed at the time of a withdrawal from estrogen,” says Dr. Maki; it’s an avenue for future research into other times of estrogen withdrawal, including the postpartum period and the late luteal stage of the menstrual cycle.
Sometimes, symptoms are short-lived. In the setting of menopause, the brain rewires and women’s cognitive abilities commonly resolve, says Dr. Maki. Yet, some women’s symptoms linger, and while some data suggests who might be more vulnerable to longer-lasting issues (more on that later), Dr. Maki says “much of that science is nascent.”
Of course, hormones aren’t solely to blame for mental health-related symptoms. Sleep disturbances—common around menopause and other times of fluctuating estrogen levels like pregnancy—can affect a whole group of cognitive functions, too, Dr. Maki explains, and hot flashes—another common menopause symptom—can also contribute to sleep issues.
Stress can also play a role. “When you have estrogen variability in the presence of a significant life stressor, those stressors will have a more negative effect,” says Dr. Maki. Those with significant life stressors during perimenopause are also disproportionately at risk for becoming depressed, she adds.
How to feel better during hormonal changes
Fortunately, there are ways to take care of your brain and mental health throughout your cycle, perimenopause, and menopause. Here are seven strategies, according to experts who study estrogen.
First: Know your symptoms are real.
Too often, women are not heard or believed in medical appointments, but research on measurable hormonal changes regularly matches women’s stories. In other words: “Women’s complaints of forgetfulness correlate with performance on tests of verbal learning and memory,” explains Dr. Maki. “The subjective complaint is, in fact, related to objective performance on these tests.” Adds Dr. Daniel: The research is clear that symptoms are not in your head. “These are real symptoms, and the loss of estrogens is likely one contributor,” says Dr. Daniel.
Find a provider who understands menopause.
Historically, physicians are not given extensive training on menopause. “It’s a women’s rights issue that we do not have these practitioners trained; it’s a huge gap,” says Dr. Maki. She recommends considering getting your general medical care from an ob-gyn (vs a primary care provider or family medicine doctor), who may have a deeper understanding of menopause-related changes in your midlife.
The Menopause Society and Let’s Talk Menopause also have databases of specially trained providers—because not all ob-gyns are trained specifically in menopause care. Working with a trained provider, even before menopause, is important as research suggests that depression and other brain-related symptoms can occur throughout perimenopause. Says Dr. Maki: “We may need, scientifically, to move our spotlight earlier in women’s lives to make sure we’re seeing when the onset of these symptoms is.”
Look back on your life to get an idea of what could lay ahead.
Felt depressed when you were first pregnant? That could be an indicator that you’re sensitive to the onboarding of hormones, explains Dr. Maki. Struggled postpartum? It could be that you are more sensitive to a drop off in hormones. According to research, about 59% of women with a past history of clinical depression also experience a recurrence of their depression during perimenopause, she says, noting that the recommended treatment for women with a history of depression who experience a recurrence is what worked in the past for them. Other stressors such as a culture focused on beauty and youthfulness that doesn’t embrace aging, or fertility issues, could also present added stress at times of estrogen fluctuations, says Dr. Maki. “You have to personalize your treatment.” A big part of that is understanding yourself and your history.
Consider hormone therapy.
In the early 2000s, The National Institutes for Health published a large clinical trial called the Women’s Health Initiative, which, among other things, found that women on hormone therapy (sometimes called hormone replacement therapy or HRT) had an increased risk of dementia and other negative outcomes, such as blood clots and stroke.
“The recommendation, then, was that women shouldn’t take hormones,” explains Dr. Daniel. But there was backlash against the research because of its design—namely that it included giving women in their 60s and 70s HRT. “That’s not how women use hormones,” says Dr. Daniel. “As people look back at the data, what’s most evident is that the women in their 50s, the younger postmenopausal women, were fine taking the hormones.”
Today, FDA-approved hormone therapy is the gold standard treatment for hot flashes and considered safe when started before age 60 or within 10 years of the start of menopause. (Though there are some medical conditions that may make hormone therapy unsafe for you, like a history of blood clots, so it’s critical to consult with your provider to find the best treatment for you.)
However, Dr. Maki notes that none of the large clinical trials have examined whether hormone therapy improves memory in women with hot flashes. That said, there could be potential: One proof-of-concept study of Dr. Maki determined that treating hot flashes—in the case of the study, with a non-hormonal intervention—improved memory to the extent that the hot flashes improved. “We’ve published studies showing that the more hot flashes you have, the worse your memory performance, the more your brain circuitry has to work to sustain your memory performance, the more Alzheimer’s disease markers we observe in blood, and the more tiny stroke-like lesions you have in the brain.” If you don’t have any symptoms? “We have four clinical trials that show that [hormone therapy] is not beneficial for cognition in women with minimal to no hot flashes.”
Know that other medications can help, too.
Oral contraceptives effectively treat hot flashes and, obviously, provide birth control; they also take away hormonal variability making them a good choice for managing the symptoms of perimenopause, says Maki. Antidepressants can also help treat clinically significant mood symptoms.
Give your body and mind some TLC.
There are plenty of lifestyle changes within your control that can help you feel your best. “Aerobic exercise has antidepressant effects, even in people with clinical depression, and it is very important for anxiety, too,” Maki says. She also favors Mindfulness Based Stress Reduction, yoga, and engaging in social activities even when you don’t feel like it. Avoiding controlled substances, like alcohol and recreational drugs, can be important too. “The perimenopausal and postmenopausal brain has this kind of ‘carryover’ effect,” she explains. “It takes longer for the effects [of substances] to wear out. So you actually often feel worse the next day.”
Get help from a mental health professional.
Maki calls therapy an “underutilized tool” in the toolbox—particularly during the perimenopausal years. Specifically, she notes that cognitive behavioral therapy can “limit the activation of the stress response system,” helping you feel better.
Again, everyone’s hormones and needs are different, so there’s no one-size-fits-all approach when hormones may be messing with your mental health. It could take a little trial and error to figure out what helps you feel your best, especially during times of major hormonal change. Just know that you don’t have to simply let haywire estrogen levels dictate your mood, memory, and overall brain power—there are lots of things you can try, and your doctor can help you figure out the best approach for you.
Related:
- Why 30 Isn’t Too Young to Start Thinking About—And Preparing for—Menopause
- Halle Berry Said a Doctor Mistook Her Perimenopause for the ‘Worst Case of Herpes’ He’d Seen
- 6 Ways to Deal With Night Sweats During Menopause
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