Lisa Mosconi is a world-renowned neuroscientist & the director of the Women’s Brain Initiative at Weill Cornell Medicine, where she studies how sex differences & hormonal transitions influence brain aging & Alzheimer’s disease risk. In this episode, Lisa explores why Alzheimer’s disease disproportionately affects women & 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, & how menopause represents a fundamental brain event that reshapes brain energy use, structure, & immune signaling. The conversation also examines what advanced brain imaging reveals about preclinical Alzheimer’s disease, estrogen receptors in the brain, & 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, & practical, evidence-based strategies to support brain health through midlife—including lifestyle, sleep, metabolism, mood, & emerging therapies such as GLP-1 agonists & SERMs (selective estrogen receptor modulators). View show notes here: https://bit.ly/3Z0fojU Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ 0:00:00-Intro 0:00:11-How Lisa became focused women’s health, brain aging, & Alzheimer’s disease (AD) 0:04:58-The long preclinical phase of AD 0:08:40-How AD compares to other common forms of dementia 0:14:36-Why AD disproportionately affects women: how AD is a midlife disease 0:25:05-Menopause as a leading explanation for women’s increased Alzheimer’s risk 0:35:38-How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition 0:49:40-What estrogen receptor imaging tells us about hormone therapy’s impact on brain health 0:59:55-Lisa’s studies on the relationship between levels of systemic estrogen & density of estrogen receptors in the brain 1:04:49-Why blood estrogen levels poorly reflect brain estrogen signaling 1:10:49-The CARE Initiative 1:13:58-The dramatic difference in AD risk between men & women associated with APOE4 1:15:13-What the evidence suggests about menopausal hormone therapy (MHT) & AD risk 1:20:57-How the CARE initiative plans to study MHT & AD risk 1:24:55-How to think about starting hormone therapy during perimenopause 1:29:10-SERMs as a targeted approach to brain health 1:33:58-Why estrogen became wrongly associated with cancer risk 1:44:09-Why better biomarkers are central to advancing women’s Alzheimer’s research 1:50:20-Modifiable risk factors 1:55:48-GLP-1 agonists & brain health 2:01:21-Strategies for women to support brain health 2:09:58-Why long-term, consistent lifestyle habits are essential for brain health -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, & all that goes into that from physical to cognitive to emotional health. With over 90 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, & more. Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan & simultaneously improving their healthspan. Learn more: https://peterattiamd.com Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies. For a full list of our registered and unregistered trademarks, trade names, and service marks, please review our Terms of Use: https://peterattiamd.com/terms-of-use/