Sanjay Gupta #4 (on dementia and weight loss drugs)

Welcome, welcome, welcome to Armchair Expert, Experts. on Expert. There is an old friend coming by. He is jockeying for most frequent guests.

He is, and he's up there.

He's in a dead heat, maybe with Sideris, yeah. Dr. Sanjay Gupta, what a sweetheart from Livonia, Michigan. That's always gonna make me like him more than everyone else.

Yeah, and he's one of those guests we have where we just start talking, and it's so interesting.

Yeah, and he can pretty much tell you about anything in the health sphere. Touchdown on the most exciting topics. In fact, today we go over Alzheimer's, the weight loss drugs.

We talked about marijuana.

Marijuanica, yeah, everything under the sun. And he has a new documentary out on May 19th on CNN called The Last Alzheimer's Patient, and we talk a lot about that. Of course, Sanjay is a neurosurgeon with a practice and CNN's chief medical correspondent. He has a new season of his podcast out now, wherever you get your podcasts, called Chasing Life, The Science Behind Happiness. Who wouldn't wanna know about that?

He's an obstetrics man.

He's an obstetrics man.

Just get out of the gym.

Yeah, sorry, I was touching my bra.

Feel solid.

Hi, so good to see you.

You too, in person.

In person, back in person. It's been a while.

Have you been offered all the drinks? I got my drink, yeah, I'm good.

You don't need a coffee or anything? No, I'm good. Tell me about your coffee intake.

I do a cup a day. I never drank coffee before the pandemic.

Okay, interesting.

Oh, in your whole life?

My whole life. Wow. Never liked it.

It's so tempting to stereotype when we have two Indians in the room. Yeah. Because Monica was a very late adapter to caffeine too.

Yeah, I also hated it.

And I immediately just go, oh, that's weird. You're two of only five people. I know that came to it that late.

Yeah.

Well, the thing is, I drank caffeine. I just didn't like coffee. Oh, tea?

Okay, so you had soda or whatever.

I'd have soda, I'd have tea. Coffee just did not taste good to me. And it was really weird, because everybody that I know, especially in the medical world, they all drink coffee. Oh, wow.

Copious amounts, you know?

Multiple cups a day. Did not like it. And then my wife started giving it to me during the pandemic.

Giving it to you like it was medicinal.

It was. I was getting up at 4.30 every morning.

Right, trying to stay on top of all the.

Make my calls to the other side of the world before they go to bed. And I needed caffeine. And I got this good coffee. Purity, I don't know if you're supposed to talk about brands. Yeah, we don't care.

What makes it unique?

The other stuff, I felt like I could always taste chemicals in the back of it. Yeah, to get that chemical aftertaste in my mouth. With Purity, it's just clean.

I want to try it. I am fully addicted to Starbees. in the same way I was addicted to Camelites. Like, it's my religion. And people even point out, like, you know, that's overly cooked and burnt, and blah, blah, blah.

You don't taste it.

It's perfect for me.

Everyone has their own palate.

Now, once you like it, because, okay, similarly, grew up my grandparents' percolator. Livonia.

I remember.

Yes.

Milford Township.

But all my summers in Livonia. And that percolator went all day long, the big coffee pot. So it smelled so good. And I wanted to like it for so long. And it was terrible, as you were just describing.

Ha, just clicked.

Don't you think that is one of the weirdest phenomena with your taste buds?

It doesn't surprise me that we are constantly changing. That our taste buds, our microbiome, what we like, what we don't like, what we find sweet or palatable changes as we get older. Frankly, it may change even day-to-day or month-to-month. We have that much sort of dynamic changes in our body. So it doesn't necessarily surprise me.

Please, tell me all day.

I mean, I'm just saying.

Okay, to put off some of that compliment, I literally just walked upstairs from the gym. So this is as good as it's gonna look for the next two days.

Did you do it just for me? Of course I did, I appreciate it.

You're bringing the brains, I gotta bring the brawn.

It's gonna be yin and yang.

You guys got both. I just wanna say I've been really looking forward to this. Us too. This is the fourth time I'm on your show.

Yeah, that's a big, you're one of our biggest.

You may have tied Sedaris with this episode, or maybe one behind.

Probably one behind.

He's four or five.

I'll be back next week. Okay.

You gotta be him. In fact, you should just come back at four and just do back-to-back. You're investigating enough things that I'm sure we could fill two hours with any number of topics. So, before we even get into that, what fascinates me about your role is you're also in show business. And so you do publicity tours.

Yeah, you know, it's funny. I've never thought of it that way. That sort of stuff was always sort of the add-on. And frankly, I'm not even really promoting anything. You guys provided this wonderful invitation.

Well, yes, May 19th, you got the last Alzheimer's patient on CNN.

I'm very excited about that.

You have a podcast of your own, Chasing Life. You have a couple of forthcoming documentaries you're making that are of great interest to me. One in particular, The Weight Loss Drugs. I want to talk about that, ad nauseum, if we could.

I want to talk about that. I just got back from Copenhagen.

Oh, you did? Yeah, so the federal government two days ago signaled that they're going to pretty much declassify. weed. Reschedule it, yeah. Reschedule it.

Tylenol level, Kristen.

Tylenol with codeine. Still controlled. So it's not recreationally going to be different than what it already is. There's so many states that have it recreationally, but it's a big move. Something we've been talking about for a long time.

Yeah, and there's also some geopolitical and historical ramifications of it. We're generally not leading this as a country. We're pretty conservative. And it's kind of shocking that we will potentially be joining a handful of countries globally out of hundreds of countries that actually might decriminalize it entirely. And that's not generally our position either.

It's not. And even this rescheduling, to be fair, we'll still have this federal versus state dichotomy. There still may be problems in certain places for people to access this as a medicine, traveling with it across state lines. That's boggled my mind, that you could use it as a legitimate medicine for your child with seizures in California, but potentially be criminalized for the same thing in a different state. So this doesn't necessarily address it, because it's still a controlled substance.

Yes, but I think we would both recognize the very well-worn pattern of this, which is most states started with a medical use clause, which then grew into recreational use. Fuck it, we're here. Let's talk about marijuana. We have now a pretty robust data set. I don't know how many years it's been, but I believe Colorado's got to be coming up on maybe a decade or something of having fully recreational legalized marijuana.

Look, you can even go further back to prohibition, because that provided some really interesting data on what happens when you actually, in that case, deregulate something. You do see usage go up for a period of time, but ultimately it probably sort of balances out to where it was before. So there's not this huge clamoring all of a sudden for people to just start taking it. People who wanted it before recreationally probably got it.

Yeah, exactly.

People who use it as a medicine and felt criminalized for using it as a medicine. By the way, I'm not just saying that. I think that not only can it work as a medicine in certain situations, I think what really struck me is that sometimes it's the only thing that can work.

Give a couple of examples.

This seizure disorder known as Dravet's, D-R-A-V-E-T-S. So it's basically just seizures that are happening all the time for young children. Intractable, they're called. And there was a little girl who first captured my attention on this, because I wasn't that sold on it being a medicine, but she was a young girl named Charlotte Figge.

Well, let's be clear. A lot of people are worshiping it as a cure-all from like the 1900s. So there's a lot of bogus stuff you had to weed through.

That's the challenge in so many areas.

Yes, almost all of these things.

I think it's one of the hardest parts of my job, frankly, because people want to see black and white where they should rightly see gray. And the idea that, well, you said it was going to be a cure-all, a panacea for everything. It's not that, therefore it's useless. Well, that's not right either. So to be nuanced in this area is challenging.

If they all hate you, I think you're onto something.

I got it.

It's like counterintuitive. It used to be that you'd think, like if you get consensus, that you were onto something, but actually I think it's the opposite now.

Yeah, you've drawn the ire of all these different people. You must be doing something right, you know?

But the young girl, sorry.

The young girl, she had tried seven different generations of anti-epileptic medications.

Keppra.

Keppra, she had done medications that had been formulated in different ways for little kids. They'd even recommended a veterinary medication, but at the same time still said cannabis was a no-no. So we're willing to try a medication for animals, but then her mom in Colorado Springs, which by the way is a pretty conservative area, parents had never used cannabis, they told me. She formulated it in her own kitchen. So just took the cannabis plant, turned it into an oil, squirted it onto her daughter's mouth, and it helped with their seizures.

Do you know, I have to remind you, Monica has epilepsy. She's-.

I've had two seizures. Nocturnal. Technically, yeah. I'm a nocturnal animal. I've had two nocturnal seizures.

Gotcha. Was the most recent one a while ago?

2020 and 2019.

Immediately before the pandemic.

Yes, right before the pandemic. And then I got on the medication. Yeah, maybe I'm just sensitive.

Clairvoyant.

To diseases.

You probably are. But did you have an aura, though? Did you have something before the actual seizure that gave you some sense?

I don't think so, because- What's an aura?

People sometimes may see a visual thing where they see sparkles in front of their eyes. Sometimes they may have a strange taste in their mouth. That's a common one. You taste metal in the back of your mouth.

Oh God, I'm gonna be so hyper-aware. Sorry, I couldn't mean to. No, they were both at night. So I don't know what anything was. And I was with friends.

I'm proud of you for keeping that in. He's a doctor. He's seen it all.

I had urinated in the bed.

Nocturnal emission of the urinary type.

That's not common for me. So I thought, what's going on? I went to the doctor the next morning. They did a urinalysis and then they were like, oh, your kidneys are fine. Everything's fine.

Did you get a scan of your brain?

No, they didn't even begin to think this could be neurological. They were just like, oh, something weird.

You laughed them out. Yeah, she drank too much. Probably. And peed in the bed a thousand times a week.

I was like, I didn't. But then the second one, and this is crazy. I was on this date, a first date. And of course I bring up that I had peed in the bed a year ago on a first date. I go all in.

They were sharing a bed, thank God.

Yeah. Got it. Thank God.

They were cutting costs, two to a bed. Bunch of millionaires still saving money. You gotta applaud it.

Seizure prophylaxis.

She was fortunate, and then they observed the whole thing.

and then went to the hospital. Then it was like, that's what's happening.

And did they scan you then?

Then they did, and everything's fine.

I had peed in the bed too, but it was alcoholism.

If I peed in the bed again, it's probably that.

Is that on your list of topics, peeing in the bed?

I just wanted to tell you that we both peed in the bed and invite you to share a similar experience.

Yeah, if you'd like to share a story about that.

I mean, I definitely peed in the bed as well.

I think I was like two years old then.

But 300 a week, that's-.

That was crazy. And so the mom-.

And by the way, if your child is having 300 seizures a week, I have to imagine you are absolutely open to anything. Oh my God.

Right, that was the thing. So, you know, she would put this baby in the BabyBjorn and just feel her seizing all the time. Can you imagine? And then they tried these medications and then they're told the medications can be cardiotoxic. They're so powerful, they could actually stop a heart.

Are they muting out neural activity of certain areas? That's right. And potentially shutting down your parasympathetic?

They're basically stunting all these pathways in your body. That's how they work. And that could have an impact on the heart as well. So she tries CBD oil and she says an hour goes by, five hours go by, a day goes by and Charlotte does not have a seizure.

She has to be crying at that point of gratitude, yeah.

Yeah, and also living with this sort of guilt still that this is a substance that shouldn't be used by a child, certainly, and was very reluctant to talk about it, but then she did. And it made a huge difference. There's a product called Charlotte's Web. You ever heard of this? It's a cannabis product, comes out of Colorado.

And being sued by the publishers of Charlotte's Web,

but hopefully they'll be victorious. Yeah, I think even the publisher of Charlotte's Web would be on board on this one.

Yeah, I hope so.

Helping a lot of kids.

Oh man.

Yeah, so that's the medical use. There are numerous ones that have been documented and are legitimate. Now, what are the more social outcomes? And have you even looked at kind of the broad data? One of the things that's been observed that I'm aware of is where marijuana is legalized, alcohol consumption dips.

There was really interesting data that came out of Colorado initially looking at opioid use specifically. And they found that opioid consumption went down.

That is wow, huh?

Part of it, I think, has to do with the fact that people do use marijuana for pain. You were getting this alternative to opioids because there weren't a lot of opioid alternatives. We've done seven documentaries on this. The last one we did was specifically looking at the use of cannabis in seniors. And it was really for what I sort of called the triad of aging.

Do you operate the farm tractor?

No, but it's so scary to take Ambien.

Yeah, it's not a good one. I'm gonna go out on a limb.

He fell, and falls are a huge problem.

How about the fact that it was never studied on women and come to find out it's twice as potent in women, for whatever reason?

I mean, the idea of how we run trials for both women and children in this country. But the idea that cannabis could be used for the nuisances of aging is really interesting.

Well, in this case, kind of a cure-all actually.

Yeah, I mean, people were reporting much higher quality of life scores. I spent a fair amount of time in Europe looking at how they're using cannabis in different places in Europe. And what is interesting. in Israel, for example, they are looking at the use of cannabis for what they call behavioral abnormalities associated with dementia. So people who get dementia oftentimes have serious behavioral problems.

And we have a really arbitrary hierarchy with what's right or wrong to take. So an antidepressant, an SSRI inhibitor designed in a lab is somehow preferable to marijuana. And I'm not team marijuana. I also think it gets a little nauseating, all the, you know, nature cures all. But it is just interesting to look at.

Yeah, why do we think it was illegal in the first place?

Coming out of prohibition, I think, frankly, just culturally, they needed another target. And I'm saying this in part because when you look at the history of that timeframe and you look at the data around cannabis, it wasn't that they said, this is problematic. What they said was, we don't have enough data to actually render a decision one way or the other. So let's just classify it, schedule it, in this case, as a schedule one substance.

It also correlated nicely with all the government's known nuisances. So your beat, poets, black folks.

I was gonna say it's a racist thing, perhaps.

Hippies, anti-war movements. Oh, they're really sawing something out there.

Oh, that sounded like a cat or something. It's like, I hate cats.

I was like, Sanjay has a weird ring on his phone.

You notice that I keep going back and forth between marijuana and cannabis. But marijuana itself is considered a piturative term that was designed to sort of diminish it even further.

Or devil's cabbage.

Yes, exactly.

The well-known phrase.

But cannabis as a actual scientific term is what scientists will often refer to it as, because they think of it as a compound that can be medicinal.

A rebrand.

A rebrand, yes. Of course, we called it weed for the documentary, so I don't think we were doing anybody any favor.

You should have just called it grass. So I'm conflicted. I kind of have to force myself to look at it in a harm reduction way because I think people are gonna use stuff. I also think there's kind of some pandemic anxiety, I think, that over-indexes in some groups and it really pairs up nicely with groups that are inheriting a lot of generational trauma. So I think it's really useful.

I agree with you on that. We run the risk of creating the same problem of over-medicalizing like we have with pharmaceuticals. I will say this, though, that after 10 years of really looking into this, we all carry these CB1 and CB2 receptors in our bodies.

The cannabinoid?

Yeah, the cannabinoid receptors. Hard one, a lot of syllables. You have it in your brain, you have it in your gut. People who have inflammatory bowel disease, for example, will sometimes find tremendous relief with cannabis. I think.

Blocks receptors.

Here, the idea that you create a homeostasis and you allow the body to sort of heal itself in some ways, I think, is interesting. The body sleeps better, it experiences less pain, it experiences less mood abnormalities, whatever it might be. He likened it to sort of a flywheel. You know, on a flywheel, you get it going and then it pretty much goes. You know, you give it a little tap every now and then, but it's gonna go.

Like creating a positive inertia.

By stimulating receptors that we all have in our bodies, these receptors exist for what? We do. create a compound in our body known as anandamide, which is probably the closest thing to cannabis that stimulates these receptors, but we only make a certain amount of that. And so the idea that you'd need to supplement as you get older because you make less of it, it's like anything else. Could you think of this like another hormone almost?

I supplement my hormones. Do you? Well, yes.

Yeah, okay.

I'm open to criticism. No. But yeah, testosterone.

Did you get your levels checked and then?

Yeah, yeah, yeah, yeah. And then I adjusted them.

They were low.

They were low. They were low. Yeah. And specifically my free testosterone was really low. Not my overall was moderately low, but my available testosterone was quite low.

What did you experience?

Most significantly, and this podcast is bizarrely a product of it. I had had a movie, came out, didn't open. well. I was in maybe like a three or four month kind of depression over that, a reevaluation. What am I doing?

Wow.

And then additionally, yeah, I put on more muscle mass. I burn fat more. I love it.

Were there any downsides?

Yeah, initially. And I think I was interviewing Andrew Huberman and he made a suggestion. So yeah, there's some pretty predictable side effects, but you can get water retention. I have that a lot. I didn't have any skin stuff that you can have.

You could tell in the gym who's using testosterone.

Just check everyone's testicles. Do you have a stance on it? Are you anti or for or pro?

Well, I just had my levels checked and they were normal, but my DHEA level was a little low. You probably had that checked as well.

Yeah, I supplement.

And it's interesting. The reason I had it checked was mostly for my brain.

Is this a result of doing your Alzheimer's piece?

Yes. I went through an entire preventive neurology.

visit in Boca Raton.

Yeah, Richard Isaacson is the guy who did this. And I got to tell you, even as a brain guy myself, it was super fascinating. I think what really jumped out at me is, first of all, because there's not a biomarker for brain health. I think if you look at heart health, you can say cholesterol, blood pressure, calcium score, ejection fraction, all these things. With brain health, the joke goes, if you ask 10 neurologists to define a healthy brain, you'll get 11 answers.

That's a very good joke. It is, but it's also scary. I know.

Because people don't really know. But the idea that we now are very comfortable saying we can prevent, predict, and treat heart disease. And that came about over the last 60, 70 years. We're sort of getting to that point with brain health now, where, even though we can't say, here is the test that definitively says whether your brain health is good or bad, we know that we can predict, prevent, and treat brain problems. And one of the things that Richard really pointed out to me was a simple equation of doing a DEXA scan of your body and seeing how much bone, how much muscle, and how much fat you have in your body.

Oh, wow.

And so someone like me, I work out every day, but I do not put on a lot of muscle. And one of the most challenging things for me is to put on skeletal muscle. So your core, you would get to the point where a preventive neurologist would say, in order for your brain health, you need to put on more muscle. Part of it might be supplementing with DHEA, in my case. Another thing might be is I do a lot of hikes with my dogs, and now I always wear a rucksack when I do that.

Well, have you read Outlive?

Yes, and he's big on that.

Yes, it's everything. And so I read that book. I guess I'm almost all in on it. Am I right in that this is a bit of a paradigm shift where we weren't looking at the brain as the result of your metabolic health. Right.

The most evidence behind brain health is exactly that.

How long has this been? To me, that felt like, oh my God, what a revelation. I'm only like a year and a half into thinking that way.

When I started my neurosurgery training, I finished in 2000.

We learned in biology when we went to college that the brain cells didn't go through mitosis, right? They were somatic cells, and then there were these gray cells that never went through mitosis. And maybe that's not true.

We can create new brain cells throughout our entire lives.

Wow, so I think I'm learning that this minute still.

Oh, wow. This is huge, this idea of neurogenesis. It's a relatively new construct, but I think that it's pretty widely accepted. We started to see this in animal studies initially, started to see it only in certain areas of the brain, including the hippocampus, which is responsible for memory, short-term memory, at least. And I think part of the issue was we didn't ever look at the healthy brain.

Whoa.

It was even a specific kind of physical activity. This was interesting, because when you work out really intensely, you can create a lot of what is called BDNF, brain-derived neurotrophic factor. That's like the miracle growth for your brain.

It's so sexy when you say these words. Yeah, I love learning this. BDNF, like they just roll right off your tongue.

You guys like this stuff.

Oh, we do.

I know, that's why I like talking to you guys.

We're brain pervs, so much of what we talk to is like.

Okay, BDNF.

Brain-derived neurotrophic factor, kind of like miracle growth for the brain. You can't eat it. You can't inject it. You have to make it. The best way to make it is through activity.

So blasts of short duration.

Short duration or just even longer duration, but less intense. Brisk walking, for example.

Okay, everything I'm reading now is like you should really be building in some really elevated heart rate. Blasts within there to increase your max VO.

Very important for overall metabolic health. Very important for heart disease. There's some nuances with the brain. That's what's sort of interesting. I think the general thinking was what's good for the heart's, good for the brain.

Like it's protecting itself.

It's protecting itself from a very high blood sugar. There's these little things about the brain that we're learning that are different.

On some level, it's really intuitive. Like when you just think of your heart in your cardiovascular system is a hydraulic system with fluid running through it. And you think of increasing the pressure at times and really forcing all of that fluid to move and circulate. There's something very intuitive about that, preventing buildup and blockage and all these things. It's interesting that you don't just intuitively apply that to your brain too.

It's always been seen as something different.

But this amyloid buildup that Alzheimer's patients seem to exhibit in fMRI scans, could we think of that amyloid as similar to any other kind of plaque you'd be building up in your cardiovascular system?

It appears to be a remnant of something. So, to the extent that coronary artery plaques, for example, are reflective or remnants of cardiac disease, I think there's a similarity. What is different here is that there are people who have a lot of amyloid plaque in their brain and have no symptoms. Oh. If you had a lot of plaque to the point of blockages, for example, in your coronary, you're most likely gonna have symptoms unless you've developed so many ancillary blood flow.

Workarounds.

Exactly. So we don't know still, if you have a lot of plaque and don't have symptoms, I think that suggested that plaque is not the whole story here. Maybe it's part of the story. And so many of the drugs that were worked on for a long time were just designed to get rid of plaque.

God, it's so hard to know, right? Is plaque a symptom of an underlying thing? that's really what we need to attack?

Some people have suggested it might even be associated with brain infections. So the plaque actually helped prevent or protect the brain against infections earlier in life, maybe.

Yeah, maybe corridor off an infection or surround or encapsulate.

Yeah, something like that, pathogen, right. Whatever it might be, or it's just some sort of remnant of something that happened in the brain. It could be an indication of the aftermath of something, as opposed to being predictive. And even when you took away the plaque, like they have these great drugs, these monoclonal antibodies, which are good at reducing the amount of plaque, but so-so. It doesn't equal?

Ah, interesting.

27% sort of slowing of cognitive decline, which is better than what we've seen before. And what Isaacson and these other preventive neurologists, and there's not many of them in the country, they believe that probably 40 to 50% of all dementias are preventable. What?

Stay tuned for more Armchair Expert, if you dare.

Yes. What happened when you went? What was the whole thing? The scan?

I gotta tell you, it was a bit scary. You guys should do it. I want to, but I am scared. You should do a podcast on this.

You won't even do the brain scan, or rather the body scan. I did the full body scan recently, and Monica's like, I don't think I want to know.

My grandpa just died and he had dementia, and so I am hyper aware that I might get it. If I can prevent it, I want to.

Yeah, and I think, again, up until recently, there wasn't the belief that you could. Right. Just like we thought about heart disease 60, 70 years ago. Either you're gonna get it or you're not. There's not much you can do.

Can I tell you something shallow and terrible about myself? I took such pleasure in watching you get some of those questions wrong. Like you're working on a little iPad and you're hitting these buttons, and sometimes there's a red X. But how do they know? it's not just that you're anxious?

Well, I was definitely anxious. I get nervous. I'm a nervous, Nelly.

Yeah, I'm a nervous test, taker.

I was comforted that you don't get every question right on every test you take. It was nice.

Are you playing Connections? I'm nervous now. No, I get nervous before everything. Do you guys get nervous?

Yeah, I do.

You don't get nervous.

It's context-dependent, for sure. When I interviewed David Letterman, my idol of my whole childhood, yeah, I'm nervous.

Because you're afraid you might not leave a good impression?

The value I have placed on what his approval would mean to me is such heightened stakes that I can't help but-.

You want him to like you.

Want that so bad. He is a father in that way. Here's somebody I've worshiped. If he even alludes to the fact that I'm doing a good job or I'm all right, that's gonna be incredible.

That's really sweet, actually. Yeah.

We should all, you know-.

Yeah, care. Yeah.

I mean, the fact that you pointed out that I got those questions wrong is gonna haunt me now for the entire play that I have.

It made me know you weren't really nitpicking on that, edit. Because if you were looking over, you'd be like, show the ones I got wrong. Right.

No, but here's a little insight that I learned about myself with this cognitive testing. So the words, you got 30 words to remember. Now, it's not just how many words you remember, it's how quickly you remember them. And which of the words did you remember? Did you gravitate away from certain words?

Welcome to the club, bud.

Do you do this? Do you do the Bs and Ds?

I'm hardcore dyslexic. Really? Oh, you didn't learn to read till fifth grade.

Interesting. So you knew that early on. I did. You developed strategies, presumably, to address it.

I don't wanna get distracted by my story, but I don't think so. I think one thing-.

It would be interesting if you took this test now to see if you've just overcome that.

I observe it constantly, though. Numbers, you know, I still have lots of jumbling, and my pronunciation's pretty rough, I think,

compared to my vocabulary. The B and D thing, that's interesting. I still go like this. Wow.

I still do this. I'm holding up a B and a D in my hand. I'll just quickly check myself.

Yeah, you definitely have it.

Like, which direction should it be pointing? The circle, is that what you're saying?

So I got the bat and the ball, and then the opposite of the bat and the ball.

Your right hand is a, and look, that's even hard for me to say really quickly.

Me too. That's a D. That's a D.

And your left hand makes a B. Audience, if you put your first finger and your thumb together and the remaining three fingers up in the air, that's what we're talking about.

Yeah.

By the way, it works well at dinner parties, too, because bread drinks.

Oh! Oh, I like that.

You've got a whole life built around this B. This is the first I've ever seen a B.

Is that my bread, or is that the guy next to me's bread? Now, you know.

But what I would argue, why I'm quick to agree with this very light diagnosis of dyslexia. for you. I agree. Yeah, it's not as so intense. When I got labeled dyslexic at UCLA, when I had to go back and get re, you know, to get extra time on tests and stuff, you have to go through a very long eight-week evaluation thing.

I think so. I think my enunciation is good. I'm older than you are, but once I started typing, I think it obviated a lot of the problem as well, because I just knew where B and D was on the keyboard, and I'd have to think about it each time. But I don't write free style very much at all.

Okay. Do you? Yeah, every morning I write with my left hand.

You don't find it challenging?

I do, I hate it, but I have to journal. It's like my commitment.

But free writing as opposed to just typing? Correct. It's probably a very good exercise.

It probably is, yeah. And I've been doing it for 20 years.

It's probably helped with spelling and all of this stuff.

I've become such a technophile with that, because now I got everything set to the maximum parameters. It'll fill in the words for me. It'll fix the spellings for me right away. So it's one step short of just thinking it and having it right, which is next, I think.

Yeah, it's very close. Okay, so when you did this barrage of tests, you discovered perhaps you're dyslexic. That's an interesting outcome. And then what other things? Because if I were you, I would go into it pretty optimistic.

Yeah. If you think of our healthcare system as a sick care system, which I think it is, in that case, I'm doing pretty well, because I'm not sick. 95% of doctors would probably look at all my results and say, you're fine. There's nothing to do here. But I think in the spirit of prevention, to the extent that it's reasonable, you know, you're not gonna go crazy in terms of costs, but there were several places that I could be optimized.

I know this supplements.

But my doc is like, you have to flip that ratio, the omega-3 to omega-6 ratio. And here's the data to show you why that's gonna be beneficial. DHEA, wearing a rucksack. There's another thing, the longest nerves in your body are the ones that go to your feet. Most people do not pay any attention to their feet and how their feet move.

They're very handsome.

They're from here in LA, George Esquivel. So he suggested toe spacers for me. Wear toe spacers 10 minutes a day, which will really help activate these nerves, the longest nerves in your body that go to your feet. So these are not expensive things to do.

Yeah, you could cram toilet paper in there if you had to, in a pinch.

And the thing is that we wouldn't be doing the documentary unless there was data behind these recommendations. These aren't these huge, placebo-controlled, randomized, decades-long study. It's very hard to do those. But I think the data is getting really good in terms of what we can do to prevent dementia. So my grandfather had it.

Yeah, exactly.

I tested genetically for it. There's ApoE3 or ApoE4.. You should probably get that done. I know.

That's a big Atiyah marker. He's obsessed with that.

It's good to know. I mean, some people don't wanna know. Right. And I think the reason they didn't wanna know was because the second part of that question was, what do I do about it? And now I think there's something you can do about it.

Can you quickly tell me, so, yeah, the grandmother on Bennett Street, off of Merriman, Alzheimer's, young age, who's a teacher at Stevenson. Yes. What is the difference between Alzheimer's and dementia?

Alzheimer's is a type of dementia.

So you could get dementia, but it not be Alzheimer's.

Correct. There's Lewy body dementia. That was something that Robin Williams had. There is frontal temporal dementia, which is what I think Bruce Willis is dealing with.

Oh, okay.

Where he's lost his ability to speak. So it can present in different ways. Ted Turner has Lewy body dementia. So Alzheimer's is the most common, but there are other types.

There's many. In the doc, I learned 6.9 million Americans have Alzheimer's.

Yeah.

I mean, that's a tremendous amount of people.

Expected to double by the year 2050.

Because of the aging population right now.

Because we're aging. Yeah.

It's like, what's happening? Collision course. Yeah, something new in the water.

Okay, yeah. They expect 150 million people around the world to have it by 2050.. It's gonna be one of the most common neurodegenerative disorders that we deal with, which is why I think there's so much interest now in saying, hey, look, beyond the meds, which there have been a couple that have been more promising over the last 14, 15 years.

Did you cover this? I just saw something really fascinating. I guess he is a surgeon by training, but he uses ultrasound to stimulate the blood-brain barrier so that the people taking that medicine, which generally you have to take it for like 30 days to get the full dose. You can get the full dose because it opens up the blood-brain barrier for a couple hours.

Yeah, you're talking about focused ultrasound. Neil Cassell, is that who you're?

Oh, that rings a bell.

He's a neurosurgeon and he runs the Focus Ultrasound Foundation. I've been very interested in this. They use it initially to try and do to the brain what deep brain stimulation would do, except without an operation. You're just using sound waves. And then, just like you said, they were using it to basically disrupt for a period of time, the blood-brain barrier, which might allow medicines in, and, according to Neil, might also let some plaque out.

I mean, this is where it's getting crazy sci-fi. Yeah. This guy's shooting an invisible sound wave. It's opening up this invisible barrier.

in a bunch of medicines.

What is this guy? I mean, it's kind of crazy.

It's wild, but it's very effective for things like essential tremor and even Parkinson's.

Yes, oh my God, that was the thing I watched. Maybe there was a 60 Minutes on this guy.

There may have been.

There was a man that came in that had tremors. so bad, Monica, he couldn't fill out the paperwork. They could barely get the head ring on him to put him inside of the MRI, because he has to be held perfectly still so he can hit the exact region of the brain. And this guy is so overcome with these tremors, he can't do anything. Couldn't lift a glass of water up, goes into the machine, they take the ring off him, and he starts crying.

It's amazing how quickly that works. Wow.

I mean, that was one of the most powerful things I've ever seen.

You find these areas of the brain, and with Parkinson's or with essential tremor, which is what I think that patient had, you're basically overstimulating certain pathways. So, you know, you imagine, like if you're trying to hold your hand really tight, you'll start to tremor. So you're basically loosening that up. We've done that with heat, done that with electricity, deep brain stimulation, and now they're doing it with sound.

That's crazy. That is incredible.

No incision. Although they do have to shave the hair.

Worth it.

Worth, it, hair grows back.

Okay, so in the Alzheimer's doc, you go to eight different states, you go coast to coast. I was curious, how does treatment and outcomes differ around the country? Let me ask this first. Are there areas that over-index and under-index in Alzheimer's regionally?

It's very associated with age.

Not obesity?

Age is the biggest predictor right now. It's a good question about obesity. Again, Isaacson.

If it's a metabolic condition at some level.

There's clearly a relationship. Age is still the biggest predictor, but there's no question that maybe later in life, people who have metabolic dysfunction are gonna be more likely to develop it. And he would even take it a step further to say that if you have metabolic issues specifically, that's gonna be more associated with memory problems. Whereas other things might be more associated with judgment. Other things might be more associated with processing speed.

Yeah, I'd rather have my prefrontal cortex banging than my hippocampus. Forget your name, but I can still think in executive function. Get rid of my memories. If it's an either, or, I'd rather, yes.

Really, what's the point, though, if you can't remember anything?

Because you can't go to the store or manage your life without the prefrontal cortex working, but I could sit around and regale the past and then not be able to do anything.

Well, I know your daughters and stuff. It's more than just regaling.

Don't bring that up. It's always a trump card.

That's a huge part of dementia.

If people hit me with that in the sunscreen debate or my motor sports, they always trump me with the daughters.

Yeah, well.

That is the trump argument.

You know what, I wanted to target my amygdala. That's what I really want. Just get that, fuck it. If we gotta throw one over the boat, let's get rid of that.

Your amygdala's good, I think.

Mine's in its constant state of flight or flight.

You got a good emotional thermostat, I feel like.

Over time, we've gotten better at regulating it, but I think it's an overactive area of the brain from the past. Okay, so it's mostly just age, so obviously South Florida's gonna have the highest rate.

South Florida's the highest. Boca, one of the reasons I think he set up shop there is because that is where the patients are. Not to circumvent this metabolic issue, though. You know, it's funny. One of the things that he recommended, and that he did himself, was to actually use Manjaro for a while.

To get it in the ratio that's optimal.

Yes, there's not data on this yet. There's data using these types of medications for Alzheimer's.

And, by the way, earmark that, because that's my other big thing I wanna talk to you about, because you have weight loss. The weight loss stuff, yeah. Yeah, yeah, because that's the one coming out later this year that I'm excited about.

Yeah, but I think age is still the biggest predictor, but there's no question. the developed world has higher rates of dementia than other parts of the world. A lot of it has to do with how we nourish ourselves, the foods that we're putting in our body, the physical activity, the paucity of that, but I think all of that is leading to these metabolic problems. that's very associated with that.

I have to tell you, so I love the work that that doctor's doing, and I loved watching that. I gotta say, I was a, there's a woman in this, doc, Chi Chi, and what's really great about her is you interviewed her five years before. It's a really nice comp for herself. We get to actually see her five years later, having gone through this very specific, and then this differs from the other doctor that you did all the scans with. But this woman who's showing some early signs of Alzheimer's when you first meet her, she goes all in on this program.

Yeah, that was the thing that we really saw. And it was five years, so we did have this real passage of time.

When you have Alzheimer's and you're starting to already show signs of it, five years is significant, right? You're expecting to see a pretty big decline in five years.

That's right. And she had her mom and her grandma, who had both gone through this. Obviously, everyone's different, but you had some sense of how quickly they could decline, and they declined very, very fast. She went on this program. The first 20 weeks, she was essentially on a placebo.

What do we mean by objectively?

So it was all these cognitive tests that we're talking about. It was pretty sophisticated cognitive testing. So you're looking at recall, you're looking at executive functioning, you're looking at processing speed, all this stuff. There's four tests, and three of the four, she got worse on. The next 20 weeks, five months, she was on the program, which is exactly how you described it, Dax, and she improved.

I'm triggered by the vegan part of it.

It's a lot to ask of people.

And there's just a religiosity surrounding veganism. And I was vegan for a year, so let me just say I've been down that path.

Dean Ornish, who's the guy that sort of oversaw this for Chi Chi.

He started as a coronary guy?

He started as a coronary guy. He's the first guy, I think, to get a FDA approved program for reversing heart disease in the country. And now he focuses attention on the brain. And so many of the strategies are the same. Can you use some of the strategies to reverse heart disease, like we were talking about for the brain?

You acknowledge that many members of the same program did not experience either an arresting of the condition and or an improvement. So what, statistically, are we looking at?

If you really looked at the people who stuck with the program consistently and did the highest dose of it, if you want to call it that, they had the most improvement. It didn't help everybody, but it seemed to be less likely to help people who didn't have the higher dose.

This is why AA is hard to evaluate.

I was literally just about to say that. It's the same as AA.

It's 55 things you're supposed to do, right? So you go to meetings, well, how many meetings do you go to? You work these 12 steps. Do you work with a sponsor? Do you sponsor somebody?

But the more engaged you are in all of those things, yeah, the more likely you are to be sober, for sure.

Yes, it's just the dosage is hard to evaluate.

But I also think, going back to the basic conceit, that, look, it doesn't make a difference. Your brain is your brain. It's just gonna have this trajectory in life. You're gonna drain the cache of neurons as you get older. If you do certain things, you may drain it faster.

They're damn good odds compared to anything else. Let me ask you this. This is kind of a global question about your job, which is you're endlessly investigating these very specific topics. And you go all in on them and you learn everything. And you must be inclined, after each one, to fully commit to whatever that thing was.

That's a really good point. And you meet such compelling people. They're so passionate and they're almost proselytizing their particular research. So I do end up adopting a lot of things. I'm adopting a lot of the things I learned from this documentary.

It sounds like it. Then it made me wonder, have you adopted previously?

Yes, it was funny. I was just looking at. in 22 years now, I've done 56 documentaries. Fuck, 56.. Yeah, documentary slash specials.

That's the gift of your job. That's the exact same gift of our job. To regularly meet people who have dedicated themselves to something and have pursued it with such passion, it's such a contagious thing to be around. That's the hidden gift of it.

And you get to learn the why behind the what, as podcasters, the what anybody can get. But the why, like why is someone narcissistic? You know, that's next. That's what I heard.

Oh, you heard, you heard, okay. So excited.

Yeah, why does someone have good anxiety?

I think people assume that what they dedicated themselves to was objectively interesting. But I would argue nothing's objectively interesting. Your interests are informed by some other thing, likely from childhood. So I think I'm most interested in like, what salve are they trying to put on themselves through learning about this and hoping to have some sense of control over this domain. That fascinates me greatly.

I do find great joy in just pursuing knowledge, even if it doesn't have a tangible impact on my life. I don't know if this is the case for you guys, but a lot of times you get so immersed in something and then I wanna talk about it a lot. You want to talk with, right? My wife is done. Oh my God.

So yeah, you and I need to like cohabitate with our wives so that they can get a fucking break.

Right, exactly.

Any episode we do, I have to then pretty much say everything that happened to her later that day.

Yeah, because you learn so much and you know, the gift is to share it. Even non-documentary, I go cover a conflict or a natural disaster. Everybody you meet is fascinating. And these people, they've been just subjected to just these unspeakable things and then they rose up and they did amazing things. But you also realize to some extent you can't convey that.

Yeah, you get into that spooky zone we don't understand yet. Like whatever's triggering mirror neurons, whatever's happening pheromonally, all this stuff that happens with the face-to-face interaction that we barely understand.

And then the characters behind these amazing developments in our world. We hear about the developments, but the people who actually helped create these things, who they are, what they are like, what motivated them, what do they get scared by, what makes them nervous?

I wonder if we share the overall conclusion of this exploration, which is, it's really two-sided. Part of it is like, we're learning so much. But I think a bigger voice in my head, my conclusion, after 800 guests, is like, we really don't know shit. And all of this is like, a really good theory is about 59% right. I'll have one expert on.

I do, and it keeps you humble. Going back to this probabilistic thing, I think it was Kant who said, in Pure Reason of Man, I think, is that the critique of man? 1700s, and he said something along the lines of, his greatest fear for society was the false confidence, bred from an ignorance, that we live in a probabilistic world. That people want to see black and white where they should see gray. And I think that that's really interesting.

Little girl babies.

Yours are 11 and nine.

Fuck, you're good.

You are not getting dementia.

You've had a lot of great recalls. You're wasting money on the DHEA.

I want to get muscles like you.

Well, I'll get you on the whole protocol. Okay, last thought on that, and then I want to get into the weight loss, which I assume you're currently working on, or you're not done with that?

Not quite. We're getting close.

What did you say right before you applied? Oh, I've been dying for someone to tell me this, and you are the perfect person. I saw a special. It had to be 10 years ago, on 60 Minutes, and it was the most novel approach to brain tumors, and it was they would go in and inject your tumor with a known pathogen. I think even in this case, it was like herpes.

Yeah, it was a virus, exactly.

A virus so that your body would read the tumor as a pathogen and deploy its own immune system, and they were showing these tumors just dissolve in days.

Yeah.

I was like, thank God. Why do we still have tumors? What's going on with that?

That was actually out of Los Angeles. Guy named Keith Black, who was at UCLA, now at Cedars.

You do not have dementia. Continue. He just pulled that.

He's like almost bragging that he doesn't.

No, no, look, this is my world, you know, so I gotta know that stuff. So that's kind of an immunotherapy. You're basically harnessing your own immune system. You're putting a big flag, in this case, on the tumor.

Because the tumor has an invisibility. cloak around it, right? Your body, for some reason, cannot see that. that's not supposed to be there.