Women's Neurology: Perspectives from the Ann S. Bowers Women's Brain Health Initiative

Nina Miolane, PhD

(Credit: X)

In preparation for a feature on the burgeoning interest in women’s neurology as a subspecialty in collaboration with the International Journal of MS Care (IJMSC), NeurologyLive^® spoke with Nina Miolane, PhD, and Amy Kuceyeski, PhD, who are both codirectors of the Ann S. Bowers Women's Brain Health Initiative (WBHI) AI Core. The WBHI AI Core, a joint endeavor between University of California, Santa Barbara (UCSB) and Cornell University, aims to develop and apply cutting edge AI for women's health to ultimately advance scientific discovery.

Miolane, who also serves as an assistant professor of electrical and computer engineering at UCSB, leads the Geometric Intelligence Lab, which focuses on identifying geometric patterns in natural and artificial intelligence to develop advanced intelligent systems, termed Geometric AI. Her lab integrates mathematical tools from geometry, topology, computer vision, and machine learning, which are implemented into open-source packages such as Geomstats and TopoX in collaboration with the PyTorch team.

Amy Kuceyeski, PhD

(Credit: X)

Kuceyeski, who also serves as a professor of radiology at Weill Cornell Medicine and Cornell Bowers CIS, aims to understand brain function to improve diagnostic, prognostic, and therapeutic approaches for neurological disease and injury. She applies quantitative methodologies, including machine learning, to data from cutting-edge neuroimaging techniques, facilitating insights into brain mechanisms. Her research emphasizes noninvasive brain stimulation and pharmacological interventions, such as psychedelics, as potential strategies to modulate brain activity and promote neurological recovery.

What follows is an edited transcript of their commentary.

NeurologyLive: How do neurological conditions in women differ from men, and what challenges arise in treatment?

Amy Kuceyeski, PhD: We know that there are sex biases in the prevalence and symptomology of various neurological conditions, including multiple sclerosis and Alzheimer disease, where the number of afflicted women outweighs the number of men. Historically, preclinical work has been done only in male animals, which can result in a mismatch between preclinical treatment efficacy and efficacy in humans of both sexes. One example is a recently approved Alzheimer drug that was shown to be more effective in men than in women.

Nina Miolane, PhD: First, there are conditions that only affect women. Half of the world's population experience menstrual cycles, pregnancy, and menopause. And yet, we know almost nothing about how these events affect the brain. Then, there are conditions that disproportionately affect women. About 2 out of 3 patients who have Alzheimer are women. About 3 out of 4 patients who have migraines are women. Again, we do not know why. Lastly, there are conditions that differently affect women. In dementia, such as Alzheimer but also frontotemporal dementia, women tend to exhibit symptoms later than men, but when they do, they decline way more rapidly.

The lack of knowledge on women's brain health comes with lots of challenges in treatment. Indeed, medicine has been built around the "one size fits all" idea, but that is not working. When women's health factors are excluded from biomedical research, this is not without consequences. [As Kuceyeski mentioned], the latest Alzheimer drug shows positive effects mostly in men. It slows cognitive decline in 43% of men and 12% of women. We need to do better.

The lack of knowledge on women's brain health comes with lots of challenges in treatment. Indeed, medicine has been built around the "one size fits all" idea, but that is not working. When women's health factors are excluded from biomedical research, this is not without consequences.

What impact do hormonal changes, like menopause or pregnancy, have on women’s brain health?

Kuceyeski: The answer to these questions are just beginning to be answered; the data needed to address these issues have historically not existed. This year alone there were a series of papers using serial, dense sampling in pregnant individuals showing dramatic decreases in cortical thickness during pregnancy which appear to rebound somewhat after pregnancy but do not return to prepregnancy levels (for at least as far out as a few years). We are still working on interpreting these and have an urgent need to replicate this in many individuals over pregnancy and beyond. Understanding how pregnancy can change brain anatomy and physiology is imperative for maternal-child health, specifically in treating postpartum depression or anxiety.

Menopause is another area that is just beginning to be explored, as only recently are there enough datasets containing neuroimaging and menopause information to perform well-powered analyses. However, there is still a desperate need to perform serial scanning on individuals who are going through the menopausal transition to see how the corresponding shifts in hormones can impact brain structure and function in a given individual, and how this may be linked to the severity of symptoms. Having this basic understanding will contribute to the development of treatments or supportive therapy to ease this transition, which is commonly associated with “brain fog” and can be very detrimental to the individual.

Miolane: Hormones are very strong modulators of brain health. For example, the hippocampus, which is the brain structure responsible for memory, navigation and learning, is very sensitive to hormones. During the menstrual cycle, pregnancy, or menopause, the rapid changes in hormones affect this region of the brain which adapts its anatomy.

Menopause is another area that is just beginning to be explored, as only recently are there enough datasets containing neuroimaging and menopause information to perform well-powered analyses.

What are the latest findings on sex-specific risks for conditions like Alzheimer or migraine in women?

Miolane: Research on the use of hormone therapy for Alzheimer disease prevention is mixed. A recent study analyzed data involving over 6 million women who received estrogen-based therapy. The findings revealed that women who took hormones in mid-life to manage menopause symptoms had a lower risk of developing dementia compared to those who hadn’t used estrogen. However, for women who started estrogen therapy at age 65 or older, the study found no reduction in dementia risk compared to those who did not receive hormone therapy. We need prospective clinical trials to know for sure.

How can healthcare better address gender disparities in women’s brain health?

Kuceyeski: One step in the right direction is something that the NIH implemented less than 10 years ago, which is the requirement for inclusion of sex as a biological variable. This is particularly salient for preclinical treatment studies, as they have historically only used male animals in testing the efficacy of potential treatments. We have seen the downstream effects of using only male animal models in recent, high profile cases. Another major development is the increased availability of funding from both federal and private institutions specifically for women’s health research and development. Finally, we must make standard the question of sex and gender as a factor in all of our analyses - this includes looking at sex differences in brain anatomy and physiology, sex differences in treatment efficacy, and understanding how female sex hormones and their fluctuations can impact the brain across various stages in a female’s life (puberty, menstrual cycles, pregnancy, menopause and aging). In my areas of brain-behavior mapping, the question of sex and gender and how they may influence the relationship between brain anatomy/physiology and behavior or outcomes are often ignored to our detriment.

Miolane: For far too long, scientific and biomedical research has excluded women and undervalued the study of women's health. Consequently, we know far too little about women's health across the lifespans. All together, studies on health factors specific to women constitute less than half of 1% of the brain imaging literature. These knowledge gaps are even more prominent for women of color, older women, and women with disabilities. This has impacted the lives of women in ways that we are just starting to understand. We need to invest in women's health.

For far too long, scientific and biomedical research has excluded women and undervalued the study of women's health. Consequently, we know far too little about women's health across the lifespans.

Is there anything you would like to add specifically about Ann S. Bowers WBHI in its dedication for women's brain health?

Kuceyeski: We at the Ann S Bowers foundation believe that when women’s brain health is made central, we all benefit. As the codirector of the AI core, one of the central pillars of my role is in engaging the larger AI/computer science community in the pursuit of women’s brain health. Historically speaking the fields of AI and computer science are also imbalanced by sex, having more men than women researchers in this area. We at the Ann S. Bowers WBHI aim to develop a wave of trainees that are well-versed and passionate about issues related to women’s brain health, and to engage the wider AI/CS community in the pursuit of understanding the mysteries of the female brain.

We at the Ann S Bowers foundation believe that when women’s brain health is made central, we all benefit.

Miolane: The Ann S. Bowers WBHI is driven by a simple idea: progress in neuroscience will flourish when the health of men and women are valued equally. Our goal is to generate the most diverse and comprehensive collection of data ever acquired for women's brain health — to ask questions on women's health that have been overlooked for too long. First, we go broad. The WBHI creates a large-scale database of brain imaging and women's health-related phenotypes by integrating data across UC Brain Imaging Centers. Second, we get precise. In addition to collecting a snapshot of the brain on a massive number of people, what if we collect a massive amount of MRI data on individuals? Dense-sampling MRI studies that track individuals at high temporal frequencies or over extended periods of time are transforming what we know about the dynamic properties of the human brain. At the Bowers WBHI, we value deep collaborative research and gather experts from neuroscience to artificial intelligence to answer life changing questions.

Transcript edited for clarity. Look for the women's neurology feature to be published later in 2024.