Why Does Alzheimer’s Affect More Women than Men?

There’s bad news and good news: Women suffer disproportionately from Alzheimers—almost two-thirds of Alzheimer’s patients are women—but researchers are working to identify measures we might take to prevent and/or treat it. Chances are, Alzheimer’s disease has touched your life in one way or another—whether you’re related to someone with the disease, you’re a caregiver for someone who has it (it should be noted that most caregivers are also women), or you, or someone close to you, is currently coping with it.

Richard Isaacson, M.D., director of the NewYork-Presbyterian/Weill Cornell Medical Center (and its patient, family, and caregiver support site, Alzheimer’s Universe), is pioneering critical research on the underlying roots of Alzheimer’s in women. He is also leading new ways to prevent the disease in the first place, to reduce risk and delay onset, and to improve the symptoms of those currently living with the disease. When it comes to brain health, Isaacson explains that there is a lot we can do to make a difference—diet is at the top of the list of lifestyle changes he recommends, and the subject of his book, The Alzheimer’s Prevention & Treatment Diet. Here, he breaks down the signs of Alzheimer’s (vs. brain fog and other more benign memory slips), outlines the (modifiable) risk factors all women should know, and shares his recommendations for what everyone can do today to optimize the way our brains age.

A Q&A with Richard Isaacson, M.D.


What are the signs of Alzheimer’s?


Alzheimer’s is most commonly characterized by progressive short-term memory loss, along with other changes in thinking skills. Some specific examples may include misplacing objects, forgetting appointments, and not recalling specific details of recent conversations. (Of course, many people who do not have Alzheimer’s have similar experiences—see below.) It is also common for people with Alzheimer’s to develop changes in mood (such as expressing symptoms of depression, irritability, and anger) and have trouble with, or changes in, sleep.


How do you distinguish Alzheimer’s symptoms from unrelated poor memory or brain fog?


There are several reasons a person can have changes in their memory or thinking skills, and it’s important for a physician to do a thorough evaluation. For example, medical conditions such as thyroid disease, low vitamin B12, and depression can cause similar changes in cognition. Hormone changes through the menopause transition, lack of sleep, and high levels of stress can also contribute. A physician can review these potential causes, check some labs, and sometimes perform cognitive testing, a depression screen, or a brain scan to get more information to help differentiate potential causes.


What kind and how much cognitive decline, if any, is normal? At what age?


This is a tough question—science has not entirely come to an exact conclusion. As we age, the brain ages too. Certain chemical and structural changes can be related to the usual aging process: This is called “cognitive aging,” and it can manifest as occasional trouble with spoken language—like a word being on the “tip of the tongue,” which the person can remember later. Thoughts or memories may be recalled less quickly than in the past, or, if a person learns something new, it may take him/her longer to fully learn that information. These types of brain changes can occur as early as in your thirties and forties, but are more commonly seen in the fifties, sixties, and beyond. Whether or not these types of changes should be called “normal” or “age-related” or something else is still a hazy area of brain science that is actively being studied.


Who do you recommend testing for (or when), and what kind of tests?


When a person has progressive short-term memory loss, confusion with the time or date, difficulty with keeping up in a conversation, or other, more subtle, cognitive changes, it is never too early to talk to a doctor and get an evaluation. Many times, people avoid seeing a doctor out of fear, or even embarrassment—and family members also delay suggesting an evaluation for a loved one out of fear, or even denial. I encourage people to realize that changes in cognitive function as we age are so common—there is nothing at all to be ashamed about. The earlier an evaluation is performed, the earlier a diagnosis can be made, and the better a person’s health will be for it.

I believe that in the future, every person above the age of fifty or so should be screened with some sort of cognitive assessment, or have a baseline assessment done—especially if there’s a family history of Alzheimer’s disease. At this time, we have a few at-home tests (including the SAGE test); a variety of computer-based tests available on AlzU.org (like the Face Name matching test); as well as tests that can be administered in a doctor’s office that assess cognitive function. It’s still unclear, though, which are the “best” tests to use. There are also new types of brain scans that can detect changes in the brain that may be consistent with Alzheimer’s disease many years before symptoms, but these are still mostly used for research purposes. When it comes to testing for Alzheimer’s, there isn’t a one-size-fits-all answer; every person is different and the types of tests and age to start screening depends on your particular medical and family history.

“I encourage people to realize that changes in cognitive function as we age are so common—there is nothing at all to be ashamed about. The earlier an evaluation is performed, the earlier a diagnosis can be made, and the better a person’s health will be for it.”

For this reason, it’s a good idea to talk to your doctor about any concerns. In an effort to proactively take control of your brain health, it’s particularly important to ask questions and get educated about potential modifiable risk factors if you: have a relative (or multiple relatives) with Alzheimer’s; have multiple cardiovascular risk factors (like high blood pressure, diabetes, or high cholesterol); and/or are African American or Hispanic (ethnicities at a higher risk for Alzheimer’s).


Why does Alzheimer’s disproportionately affect women?


Two thirds of the brains affected by AD are women. In the past, we thought this was because women live longer than men (age is the #1 risk factor for AD). However, it’s not that simple. For example, women over the age of sixty-five who also have an APOE4 gene may be at higher risk (meaning there is an age by gene interaction). Also, menopause transition causes complex changes in the brain, so hormones may be a factor of the increased risk.

When it comes to African Americans and Latinos, it is unclear exactly why these communities are at higher risk, but it may be due to the higher incidence of vascular risk factors (like diabetes, high blood pressure, and high cholesterol). These factors (among many others, like stress and sleep deprivation) may press the “fast forward” button toward Alzheimer’s. We have a lot more to learn about what causes Alzheimer’s to develop, specifically in women, but it seems that a person can take many different roads to Alzheimer’s—and women may be more likely to be in the “express lane” whereas men are sitting in traffic.


What’s important to know about how a woman’s brain changes with hormonal shifts?


Science is still unclear as to when the optimal “window of opportunity” to consider using hormones to help protect against Alzheimer’s might be. Some believe that hormone replacement therapy may be beneficial when used earlier on during the perimenopause transition, for a short duration of time (e.g., five to ten years). However, when hormones are taken later in life, they may not be helpful, and even perhaps harmful. These decisions need to be made on an individual basis with the advice of the treating physician who considers the overall picture (e.g., medical conditions, family history of breast cancer, etc.)

There has not been much research on “younger women” per se, but a recent study we published has helped to shed some light. We used the imaging test positron emission tomography (PET) to measure the use of glucose—a principal fuel source for cellular activity—in the brains of forty-three healthy women ages forty to sixty. Of those, fifteen were pre-menopausal, fourteen were transitioning to menopause (perimenopause), and fourteen were menopausal.

“Two thirds of the brains affected by AD are women. In the past, we thought this was because women live longer than men. However, it’s not that simple.”

The tests revealed the women who had undergone menopause or were perimenopausal had markedly lower levels of glucose metabolism in several key brain regions than those who were pre-menopausal. Scientists in prior studies have seen a similar pattern of “hypometabolism” in the brains of patients in the earliest stages of Alzheimer’s—and even in mice that model the disease. In addition, menopausal and perimenopausal patients showed lower levels of activity for an important metabolic enzyme called mitochondrial cytochrome oxidase, as well as lower scores on standard memory tests. These differences were not explained by age alone; even when accounting for the fact that the menopausal and perimenopausal women were older, there was a strong contrast with the premenopausal patients.

Our findings showed that the loss of estrogen in menopause also means the loss of a key neuroprotective element in the female brain and a higher vulnerability to brain aging and Alzheimer’s disease. The findings add to mounting evidence that there is a physiological connection between menopause and Alzheimer’s.

Menopause has long been known to cause brain-related symptoms, including depression, anxiety, insomnia, and cognitive deficits. Scientists widely believe these symptoms are caused largely by declines in estrogen levels. Estrogen receptors are found on cells throughout the brain; and evidence suggests that reduced signaling through these receptors—due to low estrogen levels—can leave brain cells generally more vulnerable to disease and dysfunction.


What’s known about preventing Alzheimer’s/cognitive decline? What are the important lifestyle changes to make, and at what age can it make a difference?


There is no one “magic pill” to prevent Alzheimer’s or cognitive decline. But the combination of lifestyle changes (like regular exercise, diet, stress reduction, and sleep; and cognitive activities such as learning a new language or playing a musical instrument), plus in some cases pharmacologic interventions (e.g., specific drugs, vitamins, and supplements) may yield the biggest potential health benefit. It’s important to note that one out of every three cases of Alzheimer’s may be preventable if that person does everything right. In the other two out of three cases, it may be possible to at least delay the onset of symptoms for a period of time, through lifestyle changes and other approaches. Promising Alzheimer’s prevention clinical trials are also ongoing right now.

Genes are not our destiny, and it is possible in some cases, to win the “tug of war” against our genes. There are many different types of “Alzheimer’s genes.” Only a very small minority of cases (less than 5 percent) are caused by an early-onset Alzheimer’s gene (meaning if you have that gene, you get the disease). In over 95 percent of cases, having a gene can increase risk somewhat, but is not definitive. The most common gene is called APOE4, which can increase the chance of developing late-onset Alzheimer’s. The good news here is that lifestyle changes may work particularly well for people with the APOE4 gene, based on the landmark FINGER study. Positive lifestyle changes can include: the combination of a brain-healthy, Mediterranean-style diet with regular exercise, cognitive activities, and regular follow-up with a healthcare provider to manage vascular risk factors.

“Genes are not our destiny, and it is possible in some cases, to win the ‘tug of war’ against our genes.”

Some of the more common supplements that I may recommend include omega-3 fatty acids and B-complex vitamins, among a few others. But, again, these decisions are made on an individual basis for each patient evaluated. Also, when it comes to omega-3’s (specifically DHA and EPA), its always best to try to get these brain-healthy fats from food, especially certain types of fatty fish (e.g., wild salmon, mackerel, sardines, lake trout, etc.) a few times each week. However, when dietary intake is not enough, taking DHA and EPA supplements may be an option in some cases. To underscore: There is no one size fits all approach toward Alzheimer’s prevention, but these lifestyle changes are a terrific way to start to take better control of one’s brain health.


After a diagnosis, what can influence the way Alzheimer’s progresses? Does anything have the potential to stop or reverse cognitive decline?


While I don’t believe we have anything currently able to stop or reverse Alzheimer’s today, there are four FDA-approved drugs that can help marginally with symptoms, and there are exciting clinical trials ongoing now with new agents. Living a healthy lifestyle, and controlling vascular risk factors can help slow decline. Caregiver support and education is also essential. There is a free caregiving course on AlzU.org, and the Alzheimer’s Association website also has plentiful resources, plus a 24-hour support hotline.


Can you tell us more about the approach at the Alzheimer’s Prevention Clinic and Alzheimer’s Universe?


In our Alzheimer’s Prevention Clinic at NewYork-Presbyterian/Weill Cornell Medical Center, we craft a multi-modal comprehensive plan for each individual patient based on their genes, biology risk factors, lifestyle, etc. Ms. Smith may need therapies A, B, and C because of her genes and risk factors, but Ms. Jones may need therapies X, Y, and Z. We developed a free online course (available on AlzU.org) that summarizes this information to help educate people about what is—and what is not—in our control when it comes to Alzheimer’s prevention. It’s been shown to make a significant impact on behaviors like these related to protecting brain health.

You can find more resources on Alzheimer’s Universe: lessons that work on all devices (computer, tablet, and cell phone), cognitive screening assessments, and links to ongoing clinical trials and registries.


What research are you working on and what challenges do you encounter—is it difficult to get funding?


We are working on two general areas of research. Our women’s research program is currently funded to study seventy-five women from the ages of forty to sixty-five over the next four years, in an effort to better understand the earliest time when Alzheimer’s-related brain changes occur. As soon as we can identify these changes, we will be better able to intervene. Alzheimer’s disease starts in the brain twenty to thirty years before the first symptom of memory loss—we need to find the optimal tools to detect this, so we can intervene early.

Unfortunately, there are no funding mechanisms on a broad scale to study women under the age of forty, and limited opportunities to do this type of groundbreaking work on women over sixty-five—the concept and approach is just too new. Ideally, we should be including women from thirty to forty and women sixty-five and over, and include more than just the seventy-five women we are funded for. Hopefully, private funding sources, philanthropic organizations, and foundations will pay more attention to this unmet need and help us to fast-forward these studies and make a big impact sooner rather than later.

Additional Alzheimer’s Resources

We’ll be digging more into mental health with varied experts on goop. In the meantime, below is a roundup of places to go for more info and a few ideas if you’re looking to make a difference.

  • The Women’s Alzheimer’s Movement

    The Women’s Alzheimer’s Movement

    The Women’s Alzheimer’s Movement–WAM—was started by Maria Shriver to collaborate the efforts of researchers across the country, increase awareness about women’s increased risk for AD, educate about a brain-healthy lifestyle, and raise funds for gender-based Alzheimer’s research. With Equinox, WAM cofounded Move for Minds—a global event dedicated to engaging people in the fight against Alzheimer’s.

  • The Alzheimer’s Association

    The Alzheimer’s Association

    One of the biggest nonprofits in the Alzheimer’s field, the Alzheimer’s Association is a global organization dedicated to advancing research and providing support to all of those affected. With chapters across the nation, a hotline that’s staffed 24/7, and tons of educational programs, this is site fits many needs. Become an advocate (for federal and state initiatives), join the Walk to End Alzheimer’s, find a local support group, or donate.

  • Hilarity for Charity

    Hilarity for Charity

    Comedian Seth Rogan started Hilarity for Charity with his wife, Lauren Miller Rogan, whose mom suffered from Alzheimer’s. The charity promotes awareness and research funding, and works to engage millennials. They host comedy charity events, gathering top comedians from around the world to raise funds that directly help those most in need through their care relief grant program, which gives in-home care to Alzheimer’s patients.

  • Brigham and Women’s Hospital

    Brigham and Women’s Hospital

    The Ann Romney Center for Neurologic Diseases focuses on promoting research for five of the most complex neurological disorders—Alzheimer’s, multiple sclerosis, ALS, Parkinson’s disease, and brain tumors. The center brings together researchers and scientists from different fields to generate new therapies and breakthroughs in the treatment of brain disorders.

Richard S. Isaacson, M.D. is a specialist in the prevention and treatment of Alzheimer’s disease, with an emphasis on risk reduction and mitigation of the disease through early personalized interventions. He is the director of the Alzheimer’s Prevention Clinic at New York-Weill Cornell Medical Center, and has devoted much of his time to his educational and outreach site, AlzU.org, which offers extensive information regarding Alzheimer’s prevention and treatment, caregiving support, clinical trials, memory activities, and publications of his research. He is the author of two bestselling books—The Alzheimer’s Prevention & Treatment Diet and Alzheimer’s Treatment Alzheimer’s Prevention: A Patient & Family Guide—and has garnered international recognition for his pioneering research on the diet upon the progression of this disease.

The views expressed in this article intend to highlight alternative studies and induce conversation. They are the views of the author and do not necessarily represent the views of goop, and are for informational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.

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