Lisa Mosconi is a world-renowned neuroscientist and the director of the Women’s Brain Initiative at Weill Cornell Medicine, where she studies how sex differences and hormonal transitions influence brain aging and Alzheimer’s disease risk. In this episode, Lisa explores why Alzheimer’s disease disproportionately affects women and why longer lifespan alone does not explain their nearly twofold risk compared to men. She explains why Alzheimer’s disease may be best understood as a midlife disease for women, beginning decades before symptoms appear, and how menopause represents a fundamental brain event that reshapes brain energy use, structure, and immune signaling. The conversation also examines what advanced brain imaging reveals about preclinical Alzheimer’s disease, estrogen receptors in the brain, and why genetic risks such as APOE4 appear to affect women differently from men. Finally, Lisa discusses the nuanced evidence around menopause hormone therapy, the legacy of the WHI, her new CARE Initiative to cut women’s Alzheimer’s risk in half by 2050, and practical, evidence-based strategies to support brain health through midlife—including lifestyle, sleep, metabolism, mood, and emerging therapies such as GLP-1 agonists and SERMs (selective estrogen receptor modulators).
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We discuss:
Timestamps: There are two sets of timestamps associated with the topic list below. The first is audio (A), and the second is video (V). If you are listening to this podcast with the audio player on this page or in your favorite podcast player, please refer to the audio timestamps. If you are watching the video version on this page or YouTube, please refer to the video timestamps.
- How Lisa’s personal family history and scientific background led her to focus on the intersection of women’s health, brain aging, and Alzheimer’s disease (AD) [A: 2:45, V: 0:11];
- The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [A: 7:15, V: 4:58];
- How AD compares to other common forms of dementia: prevalence, pathology, symptoms, diagnostic challenges, and more [A: 10:45, V: 8:40];
- Why AD disproportionately affects women: how AD is not simply a disease of old age or longevity but a midlife disease in which women develop pathology earlier [A: 16:15, V: 14:36];
- Menopause as a leading explanation for women’s increased Alzheimer’s risk, and how advanced braining imaging can detect early changes in the brain [A: 26:15, V: 25:05];
- How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition [A: 35:45, V: 35:38];
- What estrogen receptor imaging can and cannot tell us about hormone therapy’s potential impact on brain health [A: 48:45, V: 49:40];
- Lisa’s studies on the relationship between levels of systemic estrogen and density of estrogen receptors in the brain [A: 58:00, V: 59:55];
- Why blood estrogen levels poorly reflect brain estrogen signaling, and how tightly regulated brain hormone dynamics complicate our understanding of menstrual-cycle and lifestyle effects [A: 1:02:15, V: 1:04:49];
- The CARE Initiative: Lisa’s research program looking to slash AD rates in women [A: 1:07:45, V: 1:10:49];
- The dramatic difference in AD risk between men and women associated with APOE4 [A: 1:10:45, V: 1:13:58];
- What the evidence suggests about menopausal hormone therapy (MHT) and AD risk, and why timing, formulation, and uterine status appear to matter [A: 1:12:00, V: 1:15:13];
- How the CARE initiative plans to study MHT and AD risk, within the practical constraints of a three-year research window [A: 1:17:30, V: 1:20:57];
- How to think about starting hormone therapy during perimenopause: balancing symptom relief, hormonal variability, and individualized care [A: 1:21:00, V: 1:24:55];
- Investigating selective estrogen receptor modulators (SERMs) as a targeted approach to brain health during and after menopause [A: 1:25:00, V: 1:29:10];
- Why estrogen became wrongly associated with cancer risk and what the evidence actually shows [A: 1:29:30, V: 1:33:58];
- Why better biomarkers are central to advancing women’s Alzheimer’s research [A: 1:38:30, V: 1:44:09];
- Modifiable risk factors for dementia, the limitations of risk models, and questionable conclusions drawn from observational data [A: 1:44:15, V: 1:50:20];
- GLP-1 agonists and brain health: exploring potential neuroprotective effects of GLP-1 agonists beyond metabolic benefits [A: 1:49:00, V: 1:55:48];
- The importance of lifestyle factors in reducing risk of dementia: practical strategies for women to support brain health [A: 1:53:45, V: 2:01:21];
- Why long-term, consistent lifestyle habits are essential for building cognitive resilience and protecting brain health over decades [A: 2:01:15, V: 2:09:58]; and
- More.
Show Notes
How Lisa’s personal family history and scientific background led her to focus on the intersection of women’s health, brain aging, and Alzheimer’s disease (AD) [A: 2:45, V: 0:11]
- This is a wonderful podcast because it combines 2 topics that we have spent a lot of time on in this podcast and in Peter’s clinical practice, but it is probably the first time we’ve brought them into an intersection here
- 1 – All things that pertain to women’s health
- In particular the transition through pre, peri, and postmenopause
- 2 – Brain health
- There isn’t a single person listening to this podcast who doesn’t appreciate both the role of the dementing diseases and how they truncate lifespan, but perhaps much more importantly, how they truncate healthspan
- The reason Peter wanted to talk with Lisa today was because she sits at the intersection of these two
- Her work is asking the questions as they pertain specifically to women and brain health
Tell me how you came to find this as your focus
- It’s quite personal for Lisa
- She was born and raised in Florence, Italy
- It’s really pretty; she never appreciated how pretty Florence is until she moved
- In Italy, many families live together
- Her parents live in Florence and her grandparents were in Florence
- Both of her parents are nuclear physicists
- She comes from an interesting family where half of the family has a PhD (usually in physics) and the other half is in the army
- Very disciplined scientists
- She grew up in this environment where everything was about physics and biology and studying and learning, and she decided to apply that knowledge to medicine
- Lisa has a PhD in neuroscience and nuclear medicine, which is a branch of radiology
- She does a lot of brain scans
- Around the time she started studying neuroscience (specifically memory and language), her grandmother (who lived with her and her parents) started showing signs of cognitive decline
- Her grandmother was the rock of the family
- She was this really strong, extremely intelligent woman who went through World War II and she raised the family
- Her grandfather was a prisoner of war, being in the army for a long time
- Nothing broke her spirit until she started losing her memory, until she started losing the ability to communicate, until she started losing the ability of taking care of the family, where she could not remember how to cook
Lisa shares, “That really broke my grandmother and broke us and led to a diagnosis of Alzheimer’s disease over time.”
- What was even scarier was that her grandmother’s 3 sisters also developed Alzheimer’s disease and passed away from it
- Her grandmother’s only brother was spared, even though they all lived to the same age (late 80s)
Peter asked, “How long did she suffer with the disease? When did it start?”
- At least a decade
- It was very subtle
- Very often Alzheimer’s disease starts in a gradual way
- At first, there’s some mild cognitive impairment, which she was able to almost masquerade
- She had strategies to find the answer, keep going about the day without really telling us that she was having a hard time
- But then it became quite evident, and, in the end, it was very severe, because she was healthy otherwise
- Her body was healthy, but her mind was not
All 3 sisters succumbed to this in their late 80s, having onset in their late 70s this is a very typical trajectory
The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [A: 7:15, V: 4:58]
Given that Lisa had such a personal experience, one of the things people often ask Peter is at what point do patients become aware of what’s happening such that it creates enormous distress for them versus when is the cognitive impairment so severe that they are no longer suffering, and it’s only those of us around them who are suffering, but we could potentially take some solace in the fact that they are no longer suffering?
Do you have a sense of that from your experience?
{end of show notes preview}
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Lisa Mosconi, Ph.D.
Lisa Mosconi, PhD, is an associate professor of neuroscience in neurology and radiology at Weill Cornell Medicine and the director of the Women’s Brain Initiative and the Alzheimer’s Prevention Clinic at Weill Cornell Medicine/New York-Presbyterian Hospital. A world-renowned neuroscientist with a PhD in neuroscience and nuclear medicine from the University of Florence in Italy, Mosconi was listed as one of the seventeen most influential living female scientists by The Times and called “the Mona Lisa of Neuroscience” by ELLE International. She is the New York Times bestselling author of The Menopause Brain and The XX Brain. Lisa has dedicated her career to understanding how risk of memory loss and dementia can be mitigated through the combination of appropriate medical care and lifestyle modifications. [Lisa Mosconi, PHD]
Instagram: dr_mosconi
TED talk: How menopause affects the brain
Website: Lisa Mosconi, PHD
