In this episode of Revolution Health Radio, Chris Kresser sits down with renowned neurologist and bestselling author Dr. David Perlmutter to discuss the emerging science of microglia—the brain's immune cells—and why they may hold the key to preventing cognitive decline and Alzheimer's disease. Drawing from his new book, Brain Defenders, Dr. Perlmutter explains how lifestyle factors such as nutrition, exercise, sleep, metabolic health, and gut health influence whether microglia protect the brain or contribute to chronic inflammation and neurodegeneration. Together, they challenge the outdated notion that dementia is largely predetermined by genetics, highlighting growing evidence that proactive lifestyle interventions can preserve—and even improve—brain function throughout life.

In this episode we discuss:

• What microglia are and why they're essential for maintaining healthy brain function
• How chronic inflammation can transform protective microglia into drivers of neurodegeneration
• The emerging science of immunometabolism and mitochondrial function
• Why insulin resistance, obesity, and type 2 diabetes dramatically increase dementia risk
• The limitations of the traditional amyloid hypothesis and what newer research suggests
• How lifestyle interventions have demonstrated measurable improvements in cognitive outcomes
• The powerful connection between the gut microbiome, systemic inflammation, and brain health
• Why sleep, exercise, and nutrition remain the most impactful tools for protecting the brain
• The truth about the APOE4 gene—and why genetics are not destiny

Show notes:

• Brain Defenders by Dr. David Perlmutter
• Dr. Perlmutter's website
• POINTER Study
• Ornish & Tanzi Alzheimer's lifestyle intervention study
• RHR: How to Sharpen and Protect Your Mind for a Lifetime, with Dale Bredesen
• RHR: Prevention and Treatment of Alzheimer's from a Functional Perspective—with Dr. Dale Bredesen
• If you'd like to ask a question for Chris to answer in a future episode, submit it here
• Follow Chris on Instagram or Facebook

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