<p><a href="https://peterattiamd.com/lisamosconi/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=260119-pod-lisamosconi&utm_content=260126-pod-lisamosconi-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&lisamosconi%20=referral&utm_campaign=260126-pod-lisamosconi&utm_content=260126-pod-lisamosconi-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=260126-pod-lisamosconi&utm_content=260126-pod-lisamosconi-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>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).</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>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];</li> <li>The long preclinical phase of AD and the emotional burden carried by patients before dementia becomes severe [7:15];</li> <li>How AD compares to other common forms of dementia: prevalence, pathology, symptoms, diagnostic challenges, and more [10:45];</li> <li>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];</li> <li>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];</li> <li>How a new method for imaging estrogen receptors in the brain is changing how we think about the menopause transition [35:45];</li> <li>What estrogen receptor imaging can and cannot tell us about hormone therapy's potential impact on brain health [48:45];</li> <li>Lisa's studies on the relationship between levels of systemic estrogen and density of estrogen receptors in the brain [58:00];</li> <li>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];</li> <li>The CARE Initiative: Lisa's research program looking to slash AD rates in women [1:07:45];</li> <li>The dramatic difference in AD risk between men and women associated with APOE4 [1:10:45];</li> <li>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];</li> <li>How the CARE initiative plans to study MHT and AD risk, within the practical constraints of a three-year research window [1:17:30];</li> <li>How to think about starting hormone therapy during perimenopause: balancing symptom relief, hormonal variability, and individualized care [1:21:00];</li> <li>Investigating selective estrogen receptor modulators (SERMs) as a targeted approach to brain health during and after menopause [1:25:00];</li> <li>Why estrogen became wrongly associated with cancer risk and what the evidence actually shows [1:29:30];</li> <li>Why better biomarkers are central to advancing women's Alzheimer's research [1:38:30];</li> <li>Modifiable risk factors for dementia, the limitations of risk models, and questionable conclusions drawn from observational data [1:44:15];</li> <li>GLP-1 agonists and brain health: exploring potential neuroprotective effects of GLP-1 agonists beyond metabolic benefits [1:49:00];</li> <li>The importance of lifestyle factors in reducing risk of dementia: practical strategies for women to support brain health [1:53:45];</li> <li>Why long-term, consistent lifestyle habits are essential for building cognitive resilience and protecting brain health over decades [2:01:15]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Implement Comprehensive Lifestyle
Proactively manage Alzheimer’s risk through a comprehensive lifestyle approach that includes diet, exercise, stress reduction, nutrition, sleep hygiene, and managing medical conditions like high blood pressure, insulin resistance, diabetes, and obesity.
2. Address Alzheimer’s Risk Early
Focus on interventions when relatively young, as the potential for delaying or preventing the accumulation of Alzheimer’s lesions in the brain is greatest before symptoms appear, as Alzheimer’s is a disease of midlife with symptoms that start in old age.
3. Prioritize Consistency in Habits
Embrace and consistently stick to brain-healthy lifestyle patterns for a long enough time, as frequent and sustained engagement is necessary to create lasting positive impacts on brain cells and resilience.
4. Women: Recognize Midlife Alzheimer’s Risk
Women should be particularly aware that Alzheimer’s disease often begins in midlife with negative brain changes, leading to symptoms much later, and women tend to show more early red flags than men.
5. Consider MHT Early for Symptoms
Consider initiating menopausal hormone therapy (MHT) as soon as symptoms appear during perimenopause, rather than waiting until full menopause, to accrue immediate benefits for vasomotor symptoms, bone health, cognitive performance, and sexual health.
6. Use MHT for Early Menopause
If experiencing premature or surgically induced menopause (e.g., oophorectomy) at a young age, hormone replacement therapy is considered the standard of care and should be used to mitigate health risks.
If considering menopausal hormone therapy, opt for transdermal estradiol with or without micronized progesterone, as this is considered the standard of care today due to a better safety profile compared to older formulations.
8. Avoid MPA in MHT
When considering menopausal hormone therapy, avoid formulations containing MPA (medroxyprogesterone acetate), as it has been linked to increased risks of breast cancer incidence and vascular damage.
9. Seek Personalized MHT Approach
When considering menopausal hormone therapy, seek a clinician who understands how to titrate doses based on individual symptoms and needs, rather than a one-size-fits-all approach.
10. Understand APOE4 Sex-Specific Risk
Women should be aware that carrying one APOE4 allele increases their dementia risk fourfold, and two APOE4 alleles increases it 12-15 times, which is approximately double the risk for men with the same genetic profile.
11. Treat Hormonal History as Vital Sign
View your hormonal history, including puberty, pregnancy, and menopause, as a vital sign that can indicate potential future cognitive decline or resilience, and discuss it with healthcare providers.
12. Address Mood Changes Proactively
Proactively address anxiety, depression, and mood changes experienced during puberty, pregnancy, or menopause, as midlife depression is a significant risk factor for Alzheimer’s, especially for women.
13. Monitor Blood Pressure Post-Preeclampsia
If you experienced pre-eclampsia during pregnancy, be vigilant about monitoring your blood pressure, as it can be a stress test indicating a higher risk for chronic hypertension and Alzheimer’s, especially during menopause.
14. Engage in Moderate Intensity Exercise
Perform moderate intensity exercise frequently enough to achieve significant health gains, as this is conducive to brain health.
15. Adjust Exercise Intensity
Prioritize higher intensity exercise if you have less time available, and distribute your efforts across lower intensities if you have more time, to optimize exercise benefits.
16. Move Regularly for Brain Health
Engage in regular physical movement to stimulate the production of BDNF and irisin in the brain, which support the health and growth of neurons and synaptic connections.
17. Reduce Inflammation & Oxidative Stress
Actively work to reduce inflammation and oxidative stress in your body, as these actions will contribute to better brain health and slower brain aging.
Aim to support healthy ATP production and reduce metabolic stress in the brain, as energetic damage can signify neurons are under stress.
19. Ensure Adequate Brain Blood Flow
Support healthy blood flow to the brain, as insufficient blood flow can be a concern for brain health.
20. Maintain Brain Volume & Hippocampus
Aim to maintain brain volume, especially in the hippocampus, as reductions in its size and density are considered a risk factor for Alzheimer’s disease.
21. Monitor White Matter Integrity
Be aware of signs of white matter integrity damage (gliosis) which can indicate inflammation or vascular insults, and monitor these as they can emerge with aging.
22. Monitor Subtle Cognitive Changes
Pay attention to subjective feelings that something is changing in your cognitive performance, even if objective tests don’t yet show impairment, as Alzheimer’s can have a preclinical phase lasting decades.
23. Explore GLP-1s for Brain Health
Stay informed about emerging research on GLP-1 agonists, as early data suggests they may reduce neuroinflammation and protein aggregation in the brain, potentially offering protection independent of weight loss or insulin sensitivity.
24. Consider MHT Post-Menopause
Women who are years past menopause may still be candidates for menopausal hormone therapy (MHT), as their brain’s estrogen receptor density may remain high, suggesting a continued appetite for estrogen.
25. Brain Estrogen Levels Are Unique
Recognize that estrogen levels in the brain are highly regulated and may not correlate directly with estrogen levels measured in the blood, which impacts understanding neurological symptoms of menopause.
26. Advocate for Breast Cancer Biomarkers
Advocate for the development of blood biomarkers for breast tissue, similar to PSA for prostate cancer, to allow for better tracking and management of breast health.
27. Advocate for MHT Research
Encourage and support more research into menopausal hormone therapy, particularly studies that provide data to guide diagnostic and treatment processes.
28. Participate in MHT Research
If you are considering starting menopausal hormone therapy, consider participating in research studies like CARE to help gather more data on its effects on Alzheimer’s biomarkers.
29. Support The Drive Podcast
Become a member at peteratiyahmd.com/subscribe to support the podcast’s ad-free content and gain access to exclusive member-only content and benefits, which aims to enhance your knowledge of health and wellness.