#381 ‒ Alzheimer’s disease in women: how hormonal transitions impact the female brain, the role of HRT, genetics, and lifestyle on risk, and emerging diagnostics and therapies | Lisa Mosconi, Ph.D.
Release Date: 01/26/2026
#381 ‒ Alzheimer’s disease in women: how hormonal transitions impact the female brain, the role of HRT, genetics, and lifestyle on risk, and emerging diagnostics and therapies | Lisa Mosconi, Ph.D.
The Peter Attia Drive
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...
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#380 ‒ The seed oil debate: are they uniquely harmful relative to other dietary fats? | Layne Norton, Ph.D.
The Peter Attia Drive
Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show’s usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL...
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#379 - AMA #79: A guide to cardiorespiratory training at any fitness level to improve healthspan, lifespan, and long-term independence
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter brings together his most up-to-date thinking on cardiorespiratory fitness into a single, practical guide designed to help listeners structure training for maximal impact on healthspan, lifespan, and long-term independence. He explains why cardiorespiratory fitness is one of the strongest modifiable predictors of longevity, clarifies what zone 2 training actually represents and how it differs from higher-intensity work, and addresses persistent confusion around exercise volume, intensity, and time constraints. The discussion covers how to...
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#378 ‒ Women’s health and performance: how training, nutrition, and hormones interact across life stages | Abbie Smith-Ryan, Ph.D.
The Peter Attia Drive
Abbie Smith-Ryan is a leading researcher in exercise physiology whose work focuses on how training and nutrition influence body composition, metabolism, cardiovascular health, and women’s health across the lifespan, with particular attention on perimenopause and post-menopause. In this episode, Abbie explains how early exercise and play help build the foundation for bone health, muscle development, and cardiorespiratory fitness in girls, as well as how puberty and menstruation shape athletic performance, motivation, and recovery. She also explores how women can tailor training and...
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Building & Changing Habits | James Clear (#183 rebroadcast)
The Peter Attia Drive
James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the “Four Laws of Behavioral Change.” In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one’s self-identity. Finally, James breaks down his...
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#377 ‒ Special episode: Understanding true happiness and the tools to cultivate a meaningful life—insights from past interviews with Arthur Brooks
The Peter Attia Drive
In this special episode of The Drive, Peter presents a curated “best of” conversation with bestselling author and previous guest Arthur Brooks, organized around four core themes: happiness itself, the forces that undermine it, the tools and practices that help cultivate it, and the courage required to live and love well. The episode brings together the most meaningful moments from two past interviews into a single, focused discussion that distills Brooks’ most insightful ideas and offers practical takeaways for building a life that's both successful and deeply happy. We discuss: ...
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#376 - AMA #78: Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter tackles a wide-ranging set of listener questions spanning lifespan interventions, exercise, cardiovascular risk reduction, time-restricted eating, blood pressure management, hormone therapy, diagnostics, and more. Peter reveals the single most important lever for extending healthspan and lifespan, and explains how he motivates midlife patients using the Centenarian Decathlon framework. He discusses the importance of addressing high apoB and cholesterol even in metabolically healthy individuals with calcium scores of zero, how to manage high...
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#375 - Ketogenic diet, ketosis & hyperbaric oxygen: metabolic therapies for weight loss, cognition, Alzheimer’s & more | Dom D’Agostino, Ph.D.
The Peter Attia Drive
Dom D'Agostino is a neuroscientist and professor at the forefront of metabolic therapies, including ketogenic diets, exogenous ketones, and hyperbaric oxygen. In this episode, Dom breaks down nutritional versus supplemental ketosis, defines meaningful ketone thresholds, and outlines practical ways to achieve ketosis. He explains how a ketogenic diet can support metabolic health and weight loss, and advises on how to maintain adequate protein and avoid common mistakes. Dom surveys the growing landscape of exogenous ketones—from salts and esters to 1,3-butanediol—and effective pairings...
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#374 - The evolutionary biology of testosterone: how it shapes male development and sex-based behavioral differences, | Carole Hooven, Ph.D.
The Peter Attia Drive
Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of...
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The impact of gratitude, serving others, embracing mortality, and living intentionally | Walter Green (#288 rebroadcast)
The Peter Attia Drive
Walter Green is a remarkable philanthropist, mentor, author of This Is the Moment!, and founder of the impactful “Say It Now” movement. In this episode, Walter delves into the unique insights gained from his challenging upbringing, discusses embracing mortality, and highlights the mindset of “finishing strong.” He shares insights on intentionality, thinking in reverse, saying “no,” prioritizing relationships, and the essence of focusing on others. The conversation focuses on the “Say It Now” movement, which stresses the importance of expressing sentiments to loved ones well...
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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).
We discuss:
- 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) [2:45];
- The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [7:15];
- How AD compares to other common forms of dementia: prevalence, pathology, symptoms, diagnostic challenges, and more [10:45];
- 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 [16:15];
- Menopause as a leading explanation for women’s increased Alzheimer’s risk, and how advanced braining imaging can detect early changes in the brain [26:15];
- How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition [35:45];
- What estrogen receptor imaging can and cannot tell us about hormone therapy’s potential impact on brain health [48:45];
- Lisa’s studies on the relationship between levels of systemic estrogen and density of estrogen receptors in the brain [58:00];
- 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 [1:02:15];
- The CARE Initiative: Lisa’s research program looking to slash AD rates in women [1:07:45];
- The dramatic difference in AD risk between men and women associated with APOE4 [1:10:45];
- What the evidence suggests about menopausal hormone therapy (MHT) and AD risk, and why timing, formulation, and uterine status appear to matter [1:12:00];
- How the CARE initiative plans to study MHT and AD risk, within the practical constraints of a three-year research window [1:17:30];
- How to think about starting hormone therapy during perimenopause: balancing symptom relief, hormonal variability, and individualized care [1:21:00];
- Investigating selective estrogen receptor modulators (SERMs) as a targeted approach to brain health during and after menopause [1:25:00];
- Why estrogen became wrongly associated with cancer risk and what the evidence actually shows [1:29:30];
- Why better biomarkers are central to advancing women’s Alzheimer’s research [1:38:30];
- Modifiable risk factors for dementia, the limitations of risk models, and questionable conclusions drawn from observational data [1:44:15];
- GLP-1 agonists and brain health: exploring potential neuroprotective effects of GLP-1 agonists beyond metabolic benefits [1:49:00];
- The importance of lifestyle factors in reducing risk of dementia: practical strategies for women to support brain health [1:53:45];
- Why long-term, consistent lifestyle habits are essential for building cognitive resilience and protecting brain health over decades [2:01:15]; and
- More.
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