Don't Wait for Alzheimer's — A Neurologist's 30-Year Plan to Protect Your Brain

**David Perlmutter** (0:00)
When we recognize that 40% to 50% of adults in America who live to be age 85 will have a diagnosis of Alzheimer's disease, at 65 years and older, risk is 1 in 9 or 11% of people age 65 or older have dementia. It is almost a fully preventable situation that people shouldn't fear, that people should feel empowerment as it relates to making the right choices.

**Mark Hyman** (0:30)
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And you had this really crappy slide.

**David Perlmutter** (3:23)
All of our slides are crappy back in the day.

**Mark Hyman** (3:26)
At the conferences. And it really stuck with me. And so much of what's wrong in the brain, whether it's neurodegenerative diseases or mood disorders, the whole spectrum of brain dysfunction is in some ways tied to dysregulation of immune function and immunity and inflammation of the brain. And your new book goes really deep on this. So maybe you can kind of start out by helping us understand a few things. Why are you focusing now on this whole framework of immuno metabolism, the mitochondria and the immune system interacting in the brain as the root cause of so much of what we're seeing that's wrong in today's brains?

**David Perlmutter** (4:06)
Well, Mark, this represents, I think, for me, a significant convergence of everything that we've been talking about for such a long time.
And it's incredible because it really unifies the mechanisms that we've talked about. You mentioned the brain on fire. This embraces the idea that neuroinflammation is a central player in what makes a good brain go bad. But beyond that, well, then where does the inflammation come from? It comes from exactly what you described, those microglial cells, these brain immune cells, innate brain immune cells. Who knew that the brain had its own immune system? And we tend to think about, well, that's what makes a good brain go bad. And the reality is these cells are, I hate to say designed, but what they do on a good day is maintenance and good things. They maintain our synapses, they maintain the function of the neurons, they maintain the blood-brain barrier. So it really broadens the scope of what we would classically consider to be immune function. When you ask somebody, what does the immune system do? And the response is going to be, well, that's what comes into play when there's a challenge by a bacterial infection, viral infection, surveillance for cancer cells, whatever it may be. But the reality is that these firemen in the firehouse are doing a lot of work to maintain the fire engine when there's no fire. And I think that tends to broaden our understanding of this immune system. It has a good side and a downside. And to be very technical about it, for our discussion today, these microglial cells can exist either in a very supportive, we call it the M2 role, where they're shoring up these barriers and keeping our synapses working, or they can shift to being destructive, what I call in the book, the evil twin, the M1 configuration, where they are going around and destroying the synapses, creating that neuroinflammatory environment where the neurons can't work well anymore, and the blood brain barrier becomes more permeable, letting bad things into the brain. That said, the most empowering part of our discussion today is that the shift from being supportive to being destructive is under our control. And for me, that really represents a whole heck of a lot because it explains everything we've been talking about for so long. It explains why in grain brain, why a higher carb diet, and we'll unpack this today, is associated with activation of these microglial cells. It explains why permeability of the gut of all things, from having changes in our gut bacteria, leads to increased inflammation that will activate these microglial cells and shift them to becoming, again, the evil twin.