Alzheimer’s and Women’s Health, an Urgent Call
The Alzheimer’s epidemic
From a broad public health standpoint, in the United States alone we are well underway to a population that will grow from 5 million (today) to nearly 14 million active Alzheimer’s patients (by 2050). This number, it should be noted, doesn’t account for additional patients with other forms of cognitive impairment. Nor does it explicitly note that this scale will demand tens of millions of Americans in full-time caregiving roles.
This has been determined through the work of the UCLA biostatistics team, among others, and is of concern to many public health officials. It is also, of course, of concern to every one of us who fear these outcomes for ourselves, and for those we love.
The threat and magnitude of the numbers is underrepresented in conventional debates about Alzheimer’s disease, in terms of health care and policy. In 2011, the disease was declared a priority by the US National Institutes of Health (NIH) with the National Alzheimer’s Project Act, but it has since lost support, including the current White House administration proposals to actually decrease NIH funding by 22%.
The unacknowledged risk to half the population
Beyond the problems in under-representing the threats of Alzheimer’s, we are most worried about what’s missing altogether in the consideration of policy and care. Few discussions acknowledge that any one part of the population is at greater risk than another.
This higher-risk subset of the population is actually 50% of all Americans. The especially vulnerable population is, simply, women.
In the next three minutes, 3 people will develop Alzheimer’s. Two of them will be women.
In 2017, it’s urgent to acknowledge, investigate, and treat Alzheimer’s as a powerfully unrecognized and vital element in women’s health.
Sadly, contemporary American women’s healthcare has been pejoratively characterized as “bikini medicine” — healthcare concerned strictly with the areas of a woman’s body that would be covered by a bikini (boobs and tubes, to be clear.) No matter how clear the statistics around Alzheimer’s are: so long as a woman’s brain lies far above and beyond the bikini, it risks going unaddressed. So, at the Weill Cornell Alzheimer’s Prevention Clinic, together with the University of Arizona, we have sought to answer the question that we didn’t hear many people asking.
Why are women vulnerable?
As doctors and scientists, we can’t hope to affect personal behavior or public policy until we can understand what’s happening. Even adjusting for lengthier lifetimes, women outnumber men 2:1 in the Alzheimer’s population. No responsible scientist would recognize that as random.
In general, the disease has compound causes, from genetics, to vascular risk, to aspects of lifestyle including diet and exercise (as a neuroscientist and nutritional counsellor, I have worked for many years on the relationship between nutrition and the pathology of the disease). While it’s true that one’s brain blueprint is largely shaped by the DNA it has received from its parents, recent discoveries have led to reversing the old view that “you are your DNA” in favor of a much more complex and dynamic model.
In this new model, genes are pivotal in establishing some aspects of Alzheimer’s risk, but the disease arises as a consequence of all the choices we make, over a lifetime. Additionally, there is consensus that Alzheimer’s is not a disease of old age, but rather starts in the brain decades before any clinical symptoms, when people are in their 50’s. So, we set out to shed light on this longstanding mystery by asking: given that it’s not simply DNA, what factors differentiate women from men, specifically as we reach middle age?
The first and most obvious place to investigate was women’s fertility. Taking into account some diversity within, the biological systems and processes of fertility are common to all women. And equally ubiquitous across all women — in fact, one of the very hallmarks of women’s middle age — is the decline in fertility, and the beginning of menopause.
The role of estrogen (and the consequences of its absence)
After rigorous study — and common knowledge to any woman in menopause — it turns out that from a biological perspective, menopause affects far more than fertility. When menopausal women experience various symptoms like hot flashes, night sweats, disturbed sleep, etc. they might not realize that these symptoms originate not in the ovaries, but in the brain. Indeed — and this is the latest research from our lab — the ebb in estrogen causes the loss of a key neuroprotective element in the female brain, with an aggressively higher vulnerability to brain aging and Alzheimer’s disease.
To determine this, we used a brain imaging technique called positron emission tomography (PET) to measure the use of glucose (a principal fuel source for cellular activity) in the brains of healthy women ages 40 to 60 . Some women were premenopausal, some were transitioning to menopause (perimenopause), and others were menopausal. We also looked at a group of healthy men of the same age.
The test revealed that the women who had undergone menopause or were perimenopausal had lower levels of glucose metabolism than those who were premenopausal and markedly lower levels than age-matched men . A similar pattern of “hypometabolism” is often found in the brains of patients in the earliest stages of Alzheimer’s — and even in transgenic mice that model the disease. In straight talk: menopause causes metabolic changes in the brain that seem to increase the risk of Alzheimer’s disease.
What to do, as a woman (some good news)
Our findings indicate that women need medical attention and care in their 40’s, well in advance of any endocrine or neurological symptoms.
When women are in their 40s and 50s, there seems to be a critical window of opportunity to detect metabolic signs of higher Alzheimer’s risk — and apply strategies to reduce that risk. We urgently need to address this because addressing the long-term health of any woman means understanding and addressing the cognitive (neurological) effects of menopause.
There are currently 850 million women worldwide who are either entering perimenopause, or are already menopausal. The good news is that we can help mitigate their likelihood to suffer from dementia or Alzheimer’s. There are several things individuals, industries, and policymakers can do to address these problems.
On an individual level, there are critical interventions that any woman can take, today. There is increasing evidence that hormonal replacement therapies (HRT) may be beneficial if instituted before menopause. We strongly urge deeper research to test the efficacy and safety of HRT for treatment of early menopause. Women are wise to be cautious about any kind of major intervention, but there is increasing recognition of the possible value of HRT in maintaining the neuroprotective elements of the female brain. Just keep in mind that, as far as pharmaceuticals go, every woman is different and thus every woman should be evaluated for different, personalized treatments.
At the same time, exercise and nutrition can help support hormonal production. Many foods boost estrogen production, including flax seeds and chickpeas. Our work also indicates that to protect their brains, women likely need antioxidants in combination with strategies to maintain estrogen levels . Most fruit and vegetables are rich in antioxidant nutrients like vitamin C and vitamin E. Besides the flax seeds mentioned above (which happen to be one of the best natural sources of vitamin E), other options include citrus fruits, berries, raw cacao, almonds, Brazil nuts, and many kinds of green leafy vegetables.
On a national, global, and policy level, Alzheimer’s disease is not on the conventional maps used for women’s health. It needs to become a capitol.
Our studies at Weill Cornell Medical are only the beginning of a new line of research that will provide critical evidence for early changes in the aging female brain. These changes seem to be powerfully relevant to women’s greater risk in becoming an Alzheimer’s patient. As men’s health includes colonoscopies in middle age, women’s health in perimenopause (and beyond) demands a thorough investigation of the aging brain, and the role of estrogen in protecting it.
Although these are only first steps, we now know when to intervene in the aging process to divert the potential for developing this devastating disease. Alzheimer’s starts decades in the brain before any symptoms appear. The more we learn about what kicks off (and accelerates) the process, the more clear it becomes: it is never too soon to take care of your brain.
Thank you for reading through, and I invite you to follow me on Twitter for updates and news on these topics, as well as the upcoming release of Brain Food: The Surprising Science of Eating for Cognitive Power (Penguin Random House, 2018). Some further research and publications are also available online.
 Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Varsavsky I, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RD. Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging. Neurology 2017 Sep 26;89(13):1382–1390.
 Mosconi L, Berti V, Guyara-Quinn C, McHugh P, Petrongolo G, Osorio RS, Connaughty C, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Swerdlow RH, Brinton RD. Perimenopause and emergence of an Alzheimer’s bioenergetic phenotype in brain and periphery. PLoS One 2017 Oct 10;12(10):e0185926.