A Brain Health Q&A with Dr. Lisa Mosconi, Author of The XX Brain

Dr. Lisa Mosconi is a neuroscientist, Alzheimer’s researcher, and author of the new book The XX Brain: The Groundbreaking Science Empowering Women To Maximize Cognitive Health and Prevent Alzheimer’s Disease (Out March 10th from Avery Books). After reading an advance copy of the book, I could not wait to share more of Dr. Mosconi’s work with you here. Not only is she a leader in women’s brain health research and neuro-nutrition, she writes like a trusted girlfriend telling you the scoop, making The XX Brain as enjoyable to read as it is informative. Dr. Mosconi guides the reader through the ever-changing science of what to do and eat to prevent cognitive decline with optimism, humor, and a good dose of common sense. 

The heart of The XX Brain is the large body of research that tells the story of women’s brains—what keeps them humming along healthily and happily, and what can push us towards cognitive decline. Women are more likely to be diagnosed with Alzheimer’s and other dementias. In fact, two-thirds of all Alzheimer’s victims are female. Dr. Mosconi is leading the movement to investigate why women are especially vulnerable to Alzheimer’s.

Her first book—Brain Food: The Surprising Science of Eating for Cognitive Power—is a guide to the latest research that links nutrition with brain health. Not a week goes by that I don’t pull Brain Food off the shelf to do a deep dive into a facet of neuro-nutrition. Between the covers of The XX Brain you will find a treasure trove of practical brain health tips. I consider it required reading for anyone curious about how to enhance brain health with age, and especially for women at menopause and beyond who want to fend off Alzheimer’s and other dementias.

About Dr. Lisa Mosconi

In addition to earning PhDs in neuroscience and nuclear medicine, Dr. Mosconi is a certified Integrative Nutritionist. She is the Director of the Women’s Brain Initiative and Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College (WCMC)/NewYork-Presbyterian Hospital, where she serves as an Associate Professor of Neuroscience in Neurology and Radiology. She is also an adjunct faculty member at the Department of Psychiatry at New York University (NYU) School of Medicine, and the Department of Nutrition at NYU Steinhardt School of Nutrition and Public Health.

I caught up with Dr. Mosconi a few weeks ago to chat with her about hormone therapy, supplements, exercise, and stress, and to dive deeper into one of her areas of expertise—genetic testing for Alzheimer’s disease. Also included are questions submitted by you, my Brain Health Kitchen readers.

Direct to Consumer Testing for the APOE4, an Alzheimer’s risk gene

Annie: In the book, you mention that DNA testing for the APOE4 Alzheimer’s risk gene through Direct to Consumer (DTC) companies (such as 23andMe) can be fraught with lab error. What are the false positive and false negative rates for APOE4 testing? And how should someone look into getting confirmation if they come up with a positive APOE4 allele on one of these tests?

Dr. Lisa Mosconi: That’s a great question, and the answer is that we don’t know. DTC labs don’t share their test-retest reliability scores so we have no access to information like false positive and false negative rates. That said, a study published in Nature Communications showed that 23andMe misdiagnosed genetic markers of cancer risk, such as the BRCA gene (aka the “Angelina Jolie gene”), in 40 percent of cases—which makes the test only slightly better than tossing a coin.

At the moment, the only genetic testing that meets quality standards is carried out by CLIA-certified labs. So if you did 23andMe and turned out to be APOE4 positive, I’d recommend to ask your doctor to re-run the test via a CLIA lab.

The epidemic within an epidemic

Annie: You are clear that menopause doesn’t cause Alzheimer’s but that the hormonal changes happening during perimenopause (defined as the time period leading up to the last menstrual period, an average of 7 years for most women) are a trigger for dementia later in life. Are any of the symptoms women experience at menopause indicative of a greater risk of Alzheimer’s later? Is “brain fog” in particular linked to accelerated cognitive decline?

 LM: We don’t know for sure, but we are looking into this. About 2 years ago, we found that the brain changes occurring during perimenopause may be a trigger for Alzheimer’s later in life. We are now looking into whether specific symptoms are associated with specific brain changes, and whether the severity of symptoms is, or both. My guess would be that the more symptoms you have, the more brain regions are involved. For context, about 20% of menopausal women have no symptoms at all, whereas the remaining 80% have symptoms that range from only hot flashes to a combination of hot flashes, disturbed sleep, brain fog, mood swings and more. So it’s important to work with as many women as we can possibly recruit to better characterize these different patterns not only from a clinical perspective but also from a neurological perspective.

On taking menopausal hormone therapy (MHT)

Annie: You break down the long history of confusing studies of how hormone therapy impacts dementia risk, as well as breast cancer and cardiovascular events. Concerns raised by the most misunderstood and misinterpreted study of all—the Women’s Health Initiative (WHI)—can finally now be put to rest! But it’s clear that more and better studies are still needed. What is your interpretation of the Cache County Study that looked at both endogenous and supplemental estrogen exposure and the incidence of Alzheimer’s? And, can this study help women decide if MHT is right for them?

LM: Thank you, it was a lot of work to really clarify what happened with the WHI and which factors can help determine whether or not MHT might work for any given patient. I even have flowcharts and diagrams so that readers can sort of take the test and at least get a good sense of whether or not they are eligible for MHT, and if they are, what are the possible risks.

As for the study you mentioned, it is a fantastic confirmation that the longer you have estrogens in your body and brain, the better your cognitive performance in old age. I talk about this new research in the book as well because I think it’s so important for all women to rethink hormones as brain allies rather than only being involved in fertility/infertility. Basically, the longer your reproductive lifespan, the better for the whole of you.

Most women become fertile around age 12-13 and go through menopause in their early 50’s. However, it can be earlier, sometimes due to genetics, oftentimes due to medical interventions. For example, as many as 1 in 9 American women undergoes a hysterectomy and/or oophorectomy — the surgical removal of the uterus and/or the ovaries. Unfortunately, these procedures correlate with an increased risk of developing dementia in women.

I am not saying that women should avoid these procedures if they need them! The point is that we need to better understand what happens to our brains as we go through menopause, natural or medical, and how to protect our brains in the process. This knowledge is crucial as currently, 850 million all over the world have just entered or are about to enter menopause!

Women and supplements

Annie: I love the individualized approach to taking supplements outlined in The XX Brain, where you break down which women are most likely to benefit from specific supplements, and in which situations. As an example, could you go over omega-3 fatty acid supplements: who is most likely to benefit, and who shouldn’t bother?

LM: Omega-3 oils are potent anti-inflammatories that support the cardiovascular system while protecting your brain cells from the wear and tear that naturally occurs with aging. Omega-3 supplementation has been associated with reduced brain shrinkage, better memory, and in some studies, a lower risk of dementia.

That said, generally there is no need to take supplements unless you are deficient, or your intake from diet is too low, especially if you don’t eat fish. So there you are for who shouldn’t bother. Generally speaking, Omega-3’s are indicated for:
· Women of all ages with low blood levels of Omega-3’s.
· Women over 50 or post-menopausal, especially APOE-4 carriers. Randomized clinical trials indicate that omega-3 DHA supplementation may be particularly beneficial for APOE-4 carriers.
· Anyone who doesn’t eat fish. These diets can lead to Omega-3 deficiencies.

Women and exercise

Annie: Another aspect of the book I love is how you address the “Less Is More” attitude towards exercise, underlining recent data that shows women may get maximum benefit from moderate, not high-intensity, exercise. In your mind, what is the best exercise for the brain, and how often should this happen for a beneficial effect?

LM: According to the Centers for Disease Control, less than 40% of adults engage in a reasonable level of physical activity per week, and 20% don’t exercise at all. On top of this, women are less likely than men to exercise, likely for a variety of reasons that have to do with family expectations, raising kids, holding full time jobs while taking care of the family, higher stress levels, and women’s uncanny ability to put everybody else before us (I am guilty too).

But, there is plenty of evidence that exercise lowers the risk of cognitive decline and Alzheimer’s in both genders, and even more so in women. Encouraging data in women shows that a higher level of cardiovascular fitness at midlife was associated with very low rates of future dementia, as compared to over 30 percent of those with the lowest level of cardiovascular fitness. So that should be enough of an incentive!

In my mind, any exercise you enjoy and practice consistently is perfect. Most studies point to moderate intensity exercise a few times a week as being particularly beneficial for women’s physical and cognitive health. Personally, I love yoga, which I practice a few times a week and it really clears my head – but it looks like a combination of aerobic and more gentle exercise might work best for the long run. We’ve got to get the heart pumping a bit.

Alleviating Stress to Reduce Alzheimer’s Risk

Annie: The data is clear that those under chronic stress have smaller brains and an increased risk of Alzheimer’s. Does stress have a greater impact on a woman’s brain? Are the effects of stress reversible? You go into all the ways we can de-stress in your book, but do you think there is a distinction, in terms of effectiveness, between yoga, meditation, and other forms of mind-body medicine? And, everyone always asks me how much time in these activities is required to have an impact on brain health.

LM: Most research points to practicing mind-body practices daily for a minimum of 3 months.

Phytoestrogens and the female brain

Annie: Soy has been steeped in controversy for decades. In the book, you discuss the pros and cons of eating soy products, and exactly which soy foods to consume to boost estrogen levels, and which ones to avoid. What are your favorite whole food soy products and how do you incorporate them into your diet?

LM: Mostly, it’s miso soup, edamame, and organic soy milk in a smoothie. If you have access to really good quality soy products, then tofu can be really yummy too.

Flooding the brain with antioxidants

Annie: We are both fans of flooding the brain with antioxidants primarily from foods, not supplements. Another useful table in your book lists the foods highest in antioxidant, anti-inflammatory, and anti-microbial foods. Many of these are on my list of brain health superstar foods that are most likely to fend off Alzheimer’s. Let’s talk about turmeric, specifically. Studies have been disappointing in that one of the active ingredients, curcumin, does not pass through the blood brain barrier in therapeutic levels. The data on curcumin supplements is mixed. Do you recommend boosting turmeric in the diet specifically for Alzheimer’s prevention, and if so, how much?

LM: Turmeric, the signature spice of Indian cuisine, is a powerful antioxidant and anti-inflammatory agent that has been used for at least 5,000 years in Ayurvedic medicine against many types of pain and inflammation associated with aging. Recent evidence shows that this spice, or more specifically, its active ingredient curcumin, may help protect against cognitive loss and dementia by keeping our neurons healthy as we age.

However, the few clinical trials of curcumin supplementation have yielded negative or inconclusive results. It is possible that eating the actual spice might prove more synergistically powerful than taking an isolated ingredient.

Going full fat with dairy

Annie: In the book, you go into the pros and cons of consuming dairy products, for both full fat and those processed to remove the fat, for brain health, cardiovascular risk, and osteoporosis prevention. Since the brain-healthy diet is low in saturated fats (some say under 10%), what are the dairy products you prefer, and how do you enjoy them?

LM: Definitely yogurt, which is a great source of brain-essential nutrients and probiotics. I only eat organic, plain yogurt – especially French or Persian, and coming in a glass jar. My daughter and I usually share a cup after dinner, topped with fresh fruit or our favorite fruit butter, which is apple butter for me and strawberry-rhubarb for her.

Readers’ questions

Brain Health Kitchen readers: What are 3 simple adjustments to make now to start improving middle age fog?

LM: 1. Stay away from processed food. Stick to a healthy diet rich in fresh vegetables, fruit, whole grain, legumes, and fish, and consume meat and dairy in moderation. And drink plenty of water!
2. Keep your body moving. You don’t have to run a marathon, the female brain seems to prefer the slow burn of consistent, low-to-moderate activity.
3. Reduce stress. There are many ways to do this, which I describe in the book.

BHK readers: What are the flowers that grace the cover of The XX Brain?

LM: Those are red clovers! I chose them because the red clover is a great source of a type of phytoestrogens called isoflavones – and these isoflavones happen to be one of the very few scientifically validated, clinical trial-approved remedies for night sweats and disturbed sleep during perimenopause. They also speak to my ‘less is more’ approach to brain health: less reliance on lab-derived drugs, more focus on time-tested natural therapies. Plus, they are so pretty!

BHK readers: Is it the fluctuations of hormones at perimenopause or the lower levels that are harmful to the brain?

LM: A combination of both, but the major problem seems to be that estradiol bottoms out during menopause — and according to several lines of evidence, estradiol is the most potent of all estrogens.

(Note: Answers have been edited and condensed for clarity.)

Thank you Dr. Mosconi for all the years of research that went into bringing us The XX Brain. Read more about Dr Mosconi’s work here and pick up a copy of the book at your favorite independent bookstore or online. Stay tuned to my social media accounts (Instagram: @brainhealthkitchen, Facebook: @BrainHealthKitchen) for a giveaway of The XX Brain.