Neuroscientist REVEALS How You Can AVOID COGNITIVE DECLINE | Rudy Tanzi

You've got to think about Alzheimer's disease as a challenge of management your whole life. Yeah.

So how do you know if you're at risk?

The amyloid plaques accumulate in the brain 15 to 20 years before symptoms. Wow. So by the time someone has symptoms, has actual dementia, the plaques have already built up in the brain and now they've peaked and they've plateaued. So you have somebody where the plaque's not even growing anymore.

The horses left the barn.

Yeah, and then you're giving them a drug that hits the plaque. So I like to say from what we figured out, the plaque likes to match is the match, the trigger. The tangles are the brush fires that then spread through the brain, killing nerve cells. And what we were doing was trying to blow out the match when there was already a forest fire. And so that means that we have to back everything up. First of all, we have to diagnose Alzheimer's disease when there's pathology, not when there's symptoms. Think about if we diagnosed cancer when there were symptoms. Imagine if we did the same thing for cancer and heart disease and diabetes that we foolishly do for Alzheimer's, which is you don't have Alzheimer's until you have symptoms. You're waiting to have a heart attack, or wait till you have a two inch tumor in organ failure and invents pain and say, okay, now he has cancer and I was giving that tumor suppressor. Yeah. And that's what's happening. So of course you don't want to, somebody does not want to have the stigma of saying I have Alzheimer's disease 20 years before symptoms because you have plaques. Especially if there's nothing you can do. Right, but you could look at it like AIDS versus HIV positive. So we're coming up with terms like HABS, H-A-B-S, meaning you have amyloid beta in your brain at a level that's concerning, just like you could have some plaque around your heart without congestive heart failure. And that's when you start treating someone who will bring their cholesterol down with saying, at that point, let's bring your amyloid down. But at least our group says, don't wipe it out. Yeah, you still need some. So here's the interesting question is, you.

Know, when functional medicine, we look Upstream, you know, what's the cause? So what's the cause of the amyloid? It's not just the genes because genes can be turned on or off and. genes can be expressed in different ways depending on the inputs of the environment, diet, lifestyle, toxins. So with the amyloid, what is driving the production of all this amyloid in these patients?

And so in the rare cases of early onset familial Alzheimer's, where we found those first three genes, that's maybe one or two percent of all cases. We know that the gene mutations cause the production of a longer version of the amyloid beta protein, it's more likely to drive amyloid plaque formation. It's almost like, picture those old chemistry experiments you did when you get a crystal, when you add, you have liquid and you add something to the liquid and you instantly get a crystallization. That's called a nucleating event or a seeding event. You seed the crystal. In the brain, amyloid has to get seeded. And, in those rare cases of early onset Alzheimer's, those mutations cause a longer version of that amyloid protein that seeds amyloid more rapidly.

That's like a genetic cause.

That's a genetic cause and it's one or two percent of cases. But, that's not happening in 98-99% of cases. So, you have to ask, I say based on that, you then have to ask logically, what seeding like a crystallization event, Right? What's seeding amyloid when you don't have more of that longer form of amyloid protein like they have in the very early onset genetic cases. And what we figured out over the last 10 years is that pathogenic microbes, bacteria, yeast, viruses may be doing the seeding of the plaques where the plaques are actually forming to protect the brain. against those microbes.

So what you're saying is really heresy, right?

Pure heresy.

Heresy, which is one that we know that there's a blood-brain barrier that stuff can't get through. Two, we know that the brain is sterile.

Oh, of course, yeah. Tell the brain that.

And three, you're discovering something radical, which is this idea of a microbiome of the brain. And that there's really a trigger, which is this infection in the brain that is subtle but actually is driving this chronic long-term process of inflammation that's really the thing that causes the symptoms of Alzheimer's.

Well, yeah. I mean, in essence, what we figured out is first of all, the brain is not sterile. If you try to look for bacteria and yeast and viruses, you do find them in the brain. And when it comes to certain viruses, we see more of them in Alzheimer's brain. And we think that might be a major culprit. We used to believe that the brain didn't have a lymphatic system. Now it does. So everything we believed about the brain, no lymphatic system, wrong, completely sterile, wrong. And the way the brain accumulates microbes is, yeah, you could have the blood-brain barrier integrity go down, so they come in from the blood. And that can happen with age, the blood-brain barrier integrity starts to go downhill. It's back, you know, the gut microbiome is what helps to keep that blood-brain barrier integrity.

There's more heresy, right?

How the gut flora is affecting the brain. The gut flora is protecting the brain through the blood-brain barrier and it helps stop inflammation. Yeah. So more heresy. If it's the right gut microbiome. If it's the gut right, right. That's right. Yeah. And in fact, in our Alzheimer's Mice, where they're getting inflammation downstream of the amyloid, it's a two-way street. You start to see that the gut actually loses the bacteria like bifida and lactobacillus that you get in yogurt and probiotics. They actually start losing it, so you get this vicious cycle. But getting back to the microbial story. The viruses don't have to come from the outside. The viruses can be living, not living, but the viruses can be dormant, integrated in the genome of neurons and other cells in the brain. That's what we've seen, is that, you know, from infancy, viruses are getting or affecting you and you develop your immune system against them and antibodies, but then they lie dormant in your genome.

So it's like a herpes infection on your lip, it may be there forever. It's never kind of come out.

It has to get activated.

Have stress or infection or cold. UV, ultraviolet, like sunlight, it can get activated, right?

Right. So what we're seeing is that there are slew of viruses that are dormant in the brain and they seem to get more activated in Alzheimer's patients. And when they do, you get instant formation of amyloid plaques, more heresy, right? The field has always said it takes years for an amyloid plaque to form. It takes months in a mouse, right? We showed proof of concept. that you can get amyloid plaques to form in 15 minutes. Yeah. An hour overnight, you can get a whole region of the brain to fill with amyloid in the dish or in a mouse by just having a microbe there where the amyloid is actually being seeded to envelop the microbes and protect the resident cells from the microbial infection.

So.

So everybody's listening and wondering, oh, my God, do I have viruses in my brain?

And.

What do I do about it? Are there takeaways or things to think about how to either keep the viruses quiet or prevent the activation of the viruses?

So everyone has these virus, just what everyone has these dormant viruses and things.

You might get as a kid, infection, right?

Yeah, like roseola is a type of herpes virus. When infants get the red rash, roseola on their face. arms and that virus then inserts itself into various genomes, including in the brain. The question is why does it get activated or how does it get activated? Because you don't, the amyloid doesn't form until the virus is actually activated and you're making viral particles in the brain. We don't know, but we know that it happens more in Alzheimer's and we can look at where the virus is integrated in the genome, what parts of the genome is integrated in Alzheimer's patients versus those who are the same age who don't have Alzheimer's. And you can start to see there are common integration spots in the genome where you get the human DNA and the virus has inserted itself and integrated. And it looks like for some reason we could never have predicted that they may get integrated in areas of the genome involved with inflammation. So now you have to think maybe inflammation, which we usually think of at the end of the disease as the forest fire that's taking you out, maybe small bouts of inflammation early on could be triggering the activation of a virus that causes the plaque. And now you get this fresh course of disease plaque tangles, more inflammation, the tool is finding dementia. So we don't, and this is all totally new stuff. So we're still learning as we go.

And we do know, you know, at a higher level that what you do in your life has an impact on your immune system. Thoughts, your feelings, your diet, exercise, how you deal with stress.

Deepak and I just wrote a whole new book on that actually. Yeah, yeah, our third book is exactly on that topic.

What's the new one?

It's called the Healing Self. It's about the power of the mind and lifestyle over your immune system and health.

So the news is you actually can modify your risk by doing something before you get Alzheimer's. And you make a big point of that. You know, we're often dealing with things like after the fact, like you said, like having a heart attack and then treating it as opposed to going into the prevention. And you said that it takes, you know, 20 years before you get Alzheimer's symptoms. Your brain is already starting to deteriorate.

We have to back everything up. So, what we used to call treating plaques prevention. Because we didn't say you have the disease until you get symptoms. Now we want to back that up and say that treating plaques is treating the disease. If you have too many plaques early on and you're perfectly fine, you start treating those plaques just like you treat plaques around the heart so you don't have congestive heart failure later on. If you have HIV, you don't wait for AIDS to get rid of HIV. So it's a similar idea. So now treatment of Alzheimer's is backed up to pre-symptomatic treatment. When you see plaques, that's gonna be the future. And the FDA needs to play along with us on this. And we're not sure how's that going?

Testing or because?

Well, the FDA wants you to use an amyloid drug and make people cognitively better who already have the disease. And that's like having someone with congestive heart failure. It's hard to already- and say, make them better with Lipitor. All right, you had to use that before.

Yeah.

Or it's like someone has a two inch tumor and organ failure and say, make them live longer with a tumor suppressor. So the FDA has to get that. That's an ongoing dialogue we have to have with them. Because if they make us show that amyloid drugs used 20 years before prevent you from getting to the symptoms, how are we going to do 20, 10, even five year trials? Who's going to do that? They would cost tens of billions of dollars. And by the time they're done, say to the pharmaceutical company, thanks very much, but now your drug's off patent too. Thanks for spending $20 billion on this new drug. And it's about to go generic because it took this long. So who's gonna do it? So the FDA has to look at the genetics, look at the new Alzheimer's in a dish, look at all the data and say, if we have a safe therapy that lowers amyloid, let people take it. On top of that, now primary prevention becomes how do we stop the accumulation of amyloid in the first place, then we have to think about how.

Because that's still a little downstream. If you have someone who's got plaque, even if they don't have symptoms and you're treating that, it's still not addressing why the plaque happened in the first place.

So now we're talking about 20-year-olds. Now we're talking about teens and 20s and 30s. What can they do to know whether they're getting more viral activation, if that turns out to be the way it happens? How do you bring those viral load down? What can you do in lifestyle to turn down neuroinflammation regarding diet? gut microbiome, sleep, stress reduction, exercise, all the things that we, you know, normally talk about. And the primary prevention for this disease is going to begin in the 20s. And you're going to actively look for issues in your 30s. By the time you're in your 40s or 50s, you're seeing how much amyloid you have and you're coming up with a plan to dial it back down.

I mean, you said that, you know, 40% of people over 85 have symptoms of dementia. And that's the biggest, fastest growing segment of our population. And the costs are $200 and change billion dollars, and it's only getting worse. It's affecting 50 million people around the world. This is an epidemic.

$1 or $5 already of Medicare and Medicaid goes to Alzheimer's.

Yeah, it's more expensive than heart disease and cancer treatment.

71 million baby boomers Within five years, you're looking at three out of five dollars of Medicare, Medicaid going to Alzheimer's.

So what you're suggesting, and this is a huge issue, but you're suggesting kind of something pretty radical is that given what we already know about how the brain works and is influenced by our lifestyle and our diet and all these activities from sleep and stress and exercise and diet, these are low-cost, simple interventions that get a profound effect on this epidemic. And even the gut microbiome, like you said, we're learning about how the gut affects the brain. And so this is a very empowering message for everybody. It's not like, oh, shoot, we all have to wait around to get Alzheimer's, and we can actually do something about it. So this is an important message for someone who is a Harvard professor who's been a leader in research, who's discovered genes that could win the Nobel Prize. I mean, you are really saying something pretty radical because conventional medicine doesn't really have that approach.

No.

Fact is that you got to think about Alzheimer's disease as a challenge of management your whole life. Yeah.

So how do you know if you're at risk? Not everybody is, right? So how do you know if you're the 20 year old or 30 year old that's supposed to actually start now?

Family history, number one. I mean, if you have first degree relatives with the disease, you're at greater risk. And in the earlier their age of onset, the stronger the role of genetics versus lifestyle. But that doesn't mean that even if you have one of these mutations in the early onset familial genes like we discovered that guarantees the disease. Those mutations guarantee plaques and tangles, but we know from resilient brains People who die in their 80s, cognitively fine, but then you look in their brain and you say, whoa, this is a mess. Alzheimer's levels of plaques and tangles, how did they not get the disease? The answer in each case is no inflammation. There's no neuroinflammation in the brain. So those people were lucky, either with lifestyle or with other genes, that despite all those plaques and tangles, their brain did not react to it when there was inflammation, so they didn't get the disease. Bottom line is you can live with plaques and tangles in your brain and not get dementia.

If the inflammation doesn't turn.

So even these people who have this, you know, death sentence of Alzheimer's gene mutation that causes onset at 40 or 50 years old, if they did things to keep neuroinflammation down, they could live with a lot of plaques and tangles in the brain. Resilient brains have taught us that. So even in these dire cases where it seems hopeless, lifestyle would most likely still be able to make some difference in delaying that age.

Yeah, I recall first set of symptoms. A patient I had who had an APOE double four, which is a very strong 75% of people get Alzheimer's with that gene. And she was a health nut. She was like 90 years old. She was a dentist. She was still working. She ate perfectly. She exercised every day. She handled her stress. And she was like 90 years old and was sharp as a tack.

I know people like that too.

You know, and it's a testament to the power we have to actually influence our gene expression. and to influence neuroinflammation. And most of us have a pretty inflammatory lifestyle with very high processed food diet, high levels of sugar and starch, not enough fruits and vegetables, we don't eat enough fiber to help our gut microbiome, we don't exercise enough, we're too stressed, we don't sleep. The average American sleeps two hours less than he did 60 years ago. So all those things are things we are actually empowered to do ourselves, which is great message for people.

Right. And that's the best thing you can do no matter what your family history is. But if you have a family history, you need to take it even more seriously. And if you're, let's say someday at 40 or 50 years old, everyone gets tested. Right now it's imaging, but there might be a blood test to see what your amyloid load is in your brain. Just like cholesterol, you might need a drug to help you bring it down, or you might choose not to. you might say, I can do without the drug and you do, you know, choose lifestyle changes to bring it down. But it's going to be very similar.

To managing heart disease. How far away from tracking, you know, and testing? I mean, we now have PET scans that are $10,000 and not really practical for a lot of people.

Well, they're down to $5,000.

$5,000.

That's a big discount. Big discount. But, you know, you strap like that to millions of people, it's a lot of money. So, how far are we from having.

A test, whether it's a blood test.

Or cheaper scan or some other indicator.

Yeah, the blood tests are coming along. We might even, you know, so amyloid and tangles can be found in these vessels called exosomes. And you can even find them in urine. And you can find them, in fact, to some extent, urine is a better indicator of what's in the fluid of the brain, like it's in cerebrospinal fluid than blood is.

It's the brain. bladder connection.

Yeah, exactly. The frame bladder connection. But, you know, but there are people working on everything from urine tests to blood tests. So right now, even let's say worst case scenario, you only have the scan. And let's say, you know, the company's got less greedy and you can do this, the scan only costs $1,000 because, you know, the price also has to do with, you know, demand.

Sure.

So let's say that happens. Well, I mean, right now when you turn, A certain age, you get a breast exam. You turn a certain age, you get a colonoscopy, which is not cheap. So I'm sure at some point people, when they were first saying, oh, everyone will have a colonoscopy after 50 years old, they were like, oh, yeah, right, that's going to happen. But you know what? Now they do. And so even in the worst case scenario, it might be that by 50 you have your brain scan. Let's say we don't have any other test. And I would say that if you have a family history, you look at the first degree relatives, earliest age of onset of symptoms, subtract 20 years, and that's when you buy the first check for your amyloid. So if someone has someone in their family who had Alzheimer, is it 60 years old with symptoms, you would do the test at 40 rather than 50. So if nothing else turns up and we have to do imaging, I could still see how that could happen.

So the future of Alzheimer's could be like the future of colon cancer, which is we control a lot of it through screening, and even more than that, we develop a protocol to actually optimize your brain function, reduce neuroinflammation, reduce your risk factors, and that combined maybe with drugs that are targeted that can help, if you're high risk to actually modify it, we're looking at maybe a future of really curing Alzheimer's or really preventing it.

Right, so we like to use the mantra early prediction, meaning look at your family history to know when you need to start getting concerned. and then early detection, meaning look for the pathology that's beginning 15-20 years before symptoms, and then early intervention. So early prediction, early detection, early intervention.

Amazing.

And I think that's, you know, I mean, you know, we had a meeting with GE who has computer programs to predict when different parts of jets are going to fail or large machinery, right? And they do a very similar thing. They have algorithms they'll learn everything they can about a blade on an engine or something, and they look for the early warning signs and predictions of failure, and then optimization, early intervention to make sure the blade doesn't break while there's someone flying in a plane. But we've even talked about applying those algorithms as a learning machine mechanism, machine learning mechanism, to look at all of our data and and tell us what we have to do in that same mantra, early prediction, early detection, early intervention.

That's amazing. Speaking of early intervention, you collaborated with Dr. Deepak Chopra in doing some extraordinary research around different interventions that affect the brain, and one of them was using meditation. And you found all kinds of extraordinary things that are all things that actually help to optimize the brain, heal the brain, renew the brain, and also prevent problems down the road. Can you tell us a little bit about that research?

Yeah, we did a clinical trial where you had 30 people learning to meditate, 30 expert meditators who were teaching them, and then another 30 people who were just staying at the same resort having fun, but eating the same food. So we had a control for the diet, right?

Yeah.

And what we found was that the folks who were learning to meditate had changes in the right direction for genes involved with inflammation. We looked at the whole expression of all the genes in the genome and built maps. And they were very different for the meditation group versus the resort group. In both cases, resort was good for you. You saw nice changes in genes involved with inflammation.

So having a vacation is good.

Yeah, so vacation was good, but meditation was much better. So with meditation, you saw changes in like the anti-aging enzyme telomerase that grows the ends of your chromosomes that keeps your cells dividing longer. There was a 40% increase in telomerase activity in the expert meditators who were meditating intensively all week. There were changes in the genes involved with Alzheimer's and how amyloid protein is cleared from the brain that were also in the right direction. I mean, when I looked at all the data, if I was writing a science fiction novel, where you had to write about the future, the effects of meditation, I would not have gone as far as the results I saw.

It's pretty amazing. I mean, you think about it, you said even in the novice meditators, not like you have to be in a cave in Tibet for 20 years to see these changes. They happen within days or weeks.

This is one week.

One week.

This is all in one week.

Yeah, that's extraordinary. I found personally that applying it in my practice and to myself, it's just, been extraordinary in how it works in the brain and reduces anxiety, helps with sleep, improves mood.

Stress plays such a huge role. Stress affects your gut microbiome, which then affects your brain, which then affects your gut microbiome. And stress ties into sleep. You know, I mean, you're stressed out, so you can't sleep. And then because you can't sleep, you get stressed. And then because you're stressed, you eat.

Junk food and comfort foods. I was like a prescription for Alzheimer.

And the whole time you're forgetting to exercise. So, I mean, we just kind of described America.

Yeah.

And that's what has to change.

Yeah.

Because that's how you're going to really hit Alzheimer's in a life management scheme.

So let's talk about exercise because people really struggle with that. And one of the things that sort of changed dramatically in the landscape of the brain is the idea that we can create new brain cells and we create new connections at an age even up to death. And that is a radical change from our idea that the brain is fixed. You've got a certain number of neurons that if you lost a few in college from too much partying, well, that's too bad. Nothing you can do. Now we know that's just a false premise. And there's some very simple things like meditating or exercise. So how does exercise affect the brain and the neurogenesis?

So exercise, so specifically where we see neurogenesis, it's in pockets of the brain, right? So, the hippocampus, which is the short-term memory area of the brain. So if we use Dan Siegel's idea of the handy brain, where you have the 300 million year old brain stem, which is instincts, base instincts for survival. Then you have the midbrain, which is fears, desires, short-term memory, emotion, and that's 100 million years old. Then all the stuff here, frontal cortex, which is four million years old, that's the new stuff.

Yeah.

Right?

So we like to say intellectual brain, emotional brain and instinctive brain. Well, where we see neurogenesis, the birth of new stem cells is here and where Alzheimer's hits, Alzheimer's first hits the short-term memory area of the brain. And so how do you induce neurogenesis in that area to have more nerve cells there? Number one is exercise. What exercise does is it turns on proteins like BDNF, which is a growth factor for neurons.

It's like miracle grow for your brain.

It's like miracle grow for the brain. That's very good. But what we also found was that BDNF not only helps the nerve cells to grow, but it cleans up the area so that they can grow in a safe neighborhood. Because we did an experiment where we used a chemical, a drug that causes nerve cells to grow. It causes nerve cells to divide neurogenesis. We said, let's see if that helps a mouse that's suffering with plaques and inflammation and Alzheimer's. It's a mouse model, but at least we could see what it would do to the inflammation and when we used the drug that caused tons of new nerve cells to grow in the mouse, nothing happened. The mouse did not get better at all. Because what we saw was that the new nerve cells were being born in a battleground. It's like babies being born in the middle of a battle in a war. And they didn't survive. They died in the battleground. Whereas if you induced neurogenesis with exercise, you get two for one. You get the birth of new nerve cells and it cleaned up the area of inflammation so the nerve cells could thrive. That's amazing. And then we figured out, you know, because people always want drugs, we figured out that what exercise was doing was causing this BDNF to be turned on. So then what we did was we added the drug that causes neurogenesis plus a drug that causes BDNF to be turned on and that mimicked exercise. Yeah.

That's powerful. And going back to the stress thing, I've seen data that show that people who have higher levels of stress, their hippocampus, which is the memory center, shrinks. And when you have somebody with Cushing's disease, which is a production of cortisol, which is sort of like high stress, but they get a very shrunken hippocampus. As soon as you cut out the tumor that's causing the cortisol, their brains grow back. Cortisol kills neurons, so it's a killer. Next time you're worried or stressed about.

Something, think about your brain. That's why I worry about some genetic testing now that's direct to consumer. You can get an ApoE test done.

And then you freak out.

And let's say you told you have an E4 risk allele, you have two E4 risk factors. The NOCEBO effect alone could take you out.

Just the stress of having the gene.

It depends on the person. Some people might say, well, if I knew I had two ApoE4s, I'll definitely get eight hours of sleep and I'll definitely exercise more and I'm going to change my diet, prebiotic, probiotic, etc. So it can have a positive effect, but it can also have a negative effect. So it's going to be very interesting to see how this all plays out.

Yeah, it's true. Some of my patients don't want to.

Know and others are excited to know so they can. I wouldn't want to know because I.

Think I'm highly prone to nocebo effect. I would worry about that. I'd want to know because I could I know what to do to like.

I would just assume I have it.

And kick my own butt to get it done. Yeah, I mean, that's true. I mean, it's good. The thing is, you know, people think, well, there's one treatment for Alzheimer's and one for heart disease and one for cancer and one for diabetes. The truth is that, you know, it's not like you need different diets for each of these things, different approaches. The same thing works for everything, right? So the diet that's gonna prevent Alzheimer's.

Is also gonna prevent diabetes and cancer and heart disease.

And what's good for the heart is.

Good for the brain. throw in the pancreas as well.

Yeah, exactly. You know, in this documentary, we've talked to scientists who are looking at how to increase brain cell growth, neurogenesis, and increase connections, neuroplasticity, and they're using the nervous system as inputs to the brain to help it kind of rebuild and rewire, like music, for example. So you've looked at that. Tell us what you've learned about music.

So the amazing thing is, as this pathology spreads through the brain in Alzheimer's disease, the music memory area that's tucked inside does not get affected. So you'll see in nursing homes someone with pretty moderate to late stage Alzheimer's who can still remember how to play every song on the piano or even sing. Even remember, you know, remembering words of a song, a different type of memory of remembering. So they can't necessarily talk coherently, but.

They can sing a song.

Yeah, they can sing a song or play piano. Then this brings us to what happens in Alzheimer's, right? Sensory information is coming in from your world and the thing is you can't integrate it into your life. So in other words, you can't make sense of a smell or a sound because that association you make that comes with learning has now been devastated by the loss of neurons, the loss of synapses. So, at any moment, even listening to me speak, sensory information is going from just behind your nose, your entorhinal cortex, into that whole cortex there, into the hippocampus here. And then in the hippocampus, you have to make sense of it. And that's how you're keeping track of your day, keeping track of every moment of your day. So it used to be thought that the sensory information just couldn't be stored. that the record button didn't work. And now newer studies have shown at MIT just this past, well, just a couple of years ago, that the record button does work in these mice that are impaired because they have lots of plaque and inflammation. It turns out they can't learn the task. And it's not because you can't record the information about how to learn a certain task. you do record it, you can't play it back. So it's access. That's good news because it says that that information is still getting stored but what's going on around them in the day.

Is your hard drive still working?

Yeah, but you can't access the neurons and synapses that are storing that short-term memory that allows you to keep track of what's going on or keep track of a conversation or cooking and answering the phone. One question has become, how can we stimulate those neurons to push the play button again? And in the experiments they did in mice, they used light and they used something called optogenetics, something we couldn't do in humans. It was just to provide proof of concept. But if you look at how music memory is wired to the hippocampus in the midbrain, there's a chance that music might stimulate those neurons where you need to push the play button. So we came up with an app called Spark Memories Radio that basically, because you're going to spark it up, right? So basically what happens is you play music that the patient loved between 13 and 25 years old because that's what emotionally stimulates you and see if we can awaken that part of the brain. the brain, see if it can awaken those neurons.

Is it working?

You know, right now we have to wait for people to use the app and they write emails and tell us their experiences. But, you know, we're getting incredible emails. People who are in the early stages of the disease, who are depressed and agitated and angry, calm down. Those who are in the later stages of the disease, who who don't speak much, more vegetative, yet conscious, they tend to not want to hear music with words in it, with lyrics. They like the music that they recognize, but they'd rather hear just instrumentals. They get confused by the lyrics. And that tends to make them wake up. So, you know, we got an email from someone who said their dad, who hadn't spoken in five or six months, lying in bed, after hearing a bunch of songs from you know, when he was a teenager, one of them in particular, the song Fever. You give me fever. Yeah, you give me fever. All of a sudden, he just, for the first time in five months, started speaking and started talking about this red pickup truck that he really loved, and this girl he took out in a pickup truck, and then everything he did with the girl in the pickup truck. Oh, that's a fun one of his dates. And so it was very embarrassing, but they loved it because, you know, he was finally speaking, you know?

So the way you're saying is the music is a doorway to open access to memories and to actually cells that were sort of asleep.

And in some programs, they're going to nursing homes and playing music very loud from the time, you know, from an average time when they were teens. And then they have a doc there who's analyzing the folks. And what they're seeing is that About 15 minutes into that, you start having a conversation with a patient who normally couldn't follow a conversation at all, who's actually following a conversation again. The music is actually allowing them, it looks like, ability to access the incoming words they hear in the conversation and follow it longer.

There are four stages. If we could get to everybody in the first two, instead of the fourth one. And by the way, in this trial, we did people in the third and early fourth stages. So they were still very far along. But the reality is you go through a period where you are asymptomatic, but you already have abnormal spinal fluid and abnormal PET scans. Then you go through what's called SCI, subjective cognitive impairment, which lasts about 10 years. So we have a tremendous window, and those people, 100% of them, reverse and do beautifully, but rarely do people come in during that time because it's relative. They know there's something wrong, their spouses often notice, but they say, well, I'm not that bad yet, I'll wait.

Yeah, don't wait.

Then the third thing is called mild cognitive impairment. It should be called relatively advanced Alzheimer's disease. It's the third of four stages. And if people would simply recognize that, not wait till then, everyone could do better. And then it's the fourth and final stage, that we actually call Alzheimer's disease. So again, calling something mild cognitive impairment is like saying you have mildly metastatic cancer. It's a late stage of the problem and we'd like to get to people earlier and earlier. So as you indicated, we look at all these different things and what we're saying really is that, yes, that's what Alzheimer's is. It is your brain's attempt to deal with these ongoing insults. by producing a substance, amyloid, and the other downstream molecules like phosphotau that actually fights the insults. It fights the infections, things coming the oral microbiome, things like P. gingivalis, the neuropathologists find in the brains of patients with Alzheimer's disease. Various mold and fungal species that they find in the brains of patients with Alzheimer's disease. Herpes simplex, of course, from the lip, we find in the brains of patients with Alzheimer's disease. This is a recurrent situation with these various pathogens and with the brain's response to these pathogens.

You're basically taking all this understanding of the things that do affect the brain. And then you create a therapeutic plan that addresses it on an individual level. And I remember this article years ago called Shifting Thinking in Dementia in the Journal of the American Medical Association. And there was this great line in there where the author said, you know, there's basically categorical misclassification and etiologic imprecision. And that means that we categorize people according to symptoms, you lost your memory, not according to the etiology or cause. So this flips it upside down and is focused on medicine by cause, not by symptom. And that's what you're doing. So everybody doesn't get the same plan. If someone has mold, they get that treated. If someone has diabetes, they get that treated. If someone has a toxin, they get that treated. If someone's nutritionally deficient in this particular nutrient or that, that gets treated. So it's very individualized. So you're not just kind of throwing the same treatment at everybody. So tell us about high level. There's the foundational pieces and then there's the more therapeutic pieces. So there's diet, exercise, sleep, and stress management. and brain training, which are the sort of foundation, talk about what are the specific kinds of dietary strategies, exercise strategies, and the sleep strategies that you're using to help these patients. Because there's some really foundational research on how these things affect the brain, and of course, stress, and then brain exercise or brainer size, which is brain training.

Yeah, it's a great point. And so, as you know, when we were in the lab, way back in 2007, this guy named Mark Hyman wrote a book about, hey, you should be treating these brain diseases with these multifactorial approaches.

And the interesting thing to me— I.

Wouldn'T listen to anything that guy says, by the way. The interesting thing to me is what we found in the test tube over 30 years fits beautifully with what you published back in 2007. So what we're seeing is very much the same thing. And as you indicated, the great news here is, whereas we've always been told there's absolutely nothing you can do to prevent, reverse, or delay cognitive decline, and we hear this again and again and again. In fact, the arsenal is huge. We have a huge armamentarium. Yes, it's diet, exercise, sleep, stress, brain training, supplementation, and detoxification as the beginning. Then beyond that, there may be other things that are dependent on what we find, but those are the basics. As you indicated, you start with nutrition, that probably of all the things is the most important in terms of getting a good output. If you're getting a good outcome, if you look at Again, we're kind of coming this from the biochemical side. If you look at what is the biochemistry that it takes to make you start making synapses again and reforming those and start making your synapses work again, there are several features to it. Number one, you have to get the appropriate energy delivery. What happens, as you know, you have both the ability to burn ketones, the ability to burn glucose. Well, when you have cognitive decline, you've lost both of those. So you are literally starving your brain. You've lost the glucose because you now have insulin resistance. You've lost the ketones because your insulin is high and it's preventing you from making the ketones. You need to get those both back. You need to become keto-adapted and you need to get into ketosis, but you need to become metabolically flexible and be able to go back and forth between burning. So getting people to do that is a critical piece of this. And then it's a plant-rich, low-carb, essentially zero simple carbs, no sugar and starch. Exactly. Mildly ketogenic diet. We encourage people to measure their ketones, whether you like to do it by finger stick or you can do it by breathalyzer to get in the appropriate ketone range. Have appropriate time for autophagy, and for your glymphatics to act, in other words, appropriate time for appropriate time. Yeah.

So, tell us about autophagy and the fasting because that's really important too, right?

Yeah.

Critical. So, autophagy, you're basically recycling components of your brain that are damaged, including things like mitochondria that aren't working so well. In fact, there was a beautiful experiment a few years ago in which just preventing the autophagy of mitochondria, that alone led to Parkinson's. And, this is in animal models, of course. of course, but it shows how critical it is to get rid of the old batteries and make the new batteries. And so, this is a critical piece. And so, yes, we want to get people to have autophagy, which we do 12 to 16 hours of fasting at night. If you're APOE4 positive, we'd like to see it more 14 to 16. If you're APOE4 negative, 12 to 14 is probably good enough. And then, you can again measure your ketones. And then, it should be, as I say, plant-rich. You've got to have the phytonutrients. But you've also got to have it so that you have a high fiber diet. It turns out this is critical. This improves your glucose loads, as you know. It improves glycotoxicty. It improves your lipid status. It improves your gut microbiome. It helps with detox. Surprisingly, high fiber diets are important for a number of reasons and really critical. That's the combination. We call this KetoFlex 12-3, but you can do it any way you like as long as the bottom line is you improve those parameters. That gets you the best outcome in this in cognitive decline, restoring that insulin sensitivity, restoring the metabolic flexibility, getting the phytonutrients, helping with the detox, optimizing your gut microbiome. Lots of studies showing relationship between gut microbiome and brain function.

So important. And I think that the idea of the brain having type 3 diabetes is an interesting concept that scientists have sort of revealed from Brown University. And I think that is what we're seeing. So, you don't get fat in the brain, you get Alzheimer's. And that's what it looks like. And so cutting out the starch and the sugar, you get people off gluten, very often, and then get them on high quality protein, low toxin fish, pastured eggs, pastured meats, grass-fed meats, lots of organic produce, plant rich, very important diet. The diet is so important. And I remember I had a patient who I treated with Alzheimer's for a while. She did really quite well, and then she kind of relapsed because she had a stress event in her life. And I put her on a ketogenic diet. and she had a chef was able to afford it. And it was amazing what happened. It was like rip, bam, Winkle, the lights went on. And I was like, whoa, this stuff works. So that's very important. The diet's so critical. So talk about the kinds of exercise that are important.

It's a great point. You know, and as we do this, we're learning what works best, what works less. And so it's clear that you, by different mechanisms, aerobic, that part and the strength training. they have different and complementary features. But there's also the coordination feature, so-called neuromotor, and now we're seeing there's also an issue with blood flow. Things like Katsu bands are turning out to be helpful. As you probably know, these have been used by a number of the Olympic athletes who are training. This is where when you're doing your training, you have bands that are somewhat restrictive. They don't cut off completely the blood flow, but they are somewhat restrictive. They're basically telling your muscles you need to improve the flow. In fact, after you use these, people actually get improved flow not only to their muscles but to their brains. That's one way to go. Then, of course, E.W.A.T., exercise with oxygen therapy, where you're doing both. You're doing the exercise, but you're also delivering a higher oxygen to your brain. Again, this is a disease in which there is an insufficiency in support of this complex neuroplasticity network. As you indicated, getting the appropriate amount of insulin sensitivity, very important, but also getting the blood flow and the oxygenation. Of course, we've heard repeatedly with COVID-19, you've got all these same sorts of things are impacted. Now you've got less blood flow, you've got less oxygenation, you've got more inflammation. Unfortunately, people who've had this are at increased risk for cognitive decline and really should all be on prevention for cognitive decline.

The exercise is key because that's one of the very powerful drivers of neuroplasticity and neurogenesis. So, when you want to increase your brain's connectivity and function and cells, the best way to do it is exercise and the high intensity training, the strength training, the various kinds of oxygen supported exercise. It's actually precision exercise prescriptions too. It's not just, you know, just take a walk.

It's more than that.

And then sleep also is really important. A lot of people have sleep apnea. Many people are misfit, poor sleep quality, and sleep has a huge effect on the brain.

So talk to me about how we.

Sort of evaluate and assess sleep. Yeah, and again, there are multiple things and multiple factors that will drive the sleep down and make it less helpful. Of course, starting with the amount of sleep. So many people waking up in the middle of the night ruminating about various things. that can be addressed. As you mentioned, sleep apnea, but there are also people who have other reasons for nocturnal hypoxemia. Again, wearables are going to be very helpful here. Whether you like to use an Apple Watch or you like to use a stick an oximeter on your finger, borrow one from your physician, or you can get them online, very inexpensive. You can check to see where your oxygenation is at night. You should be sitting up in the 96% to 98%. We see people all the time that are down into the 80s and even into the 70s. These people are starving their brains for oxygen at night. It could be from sleep apnea, but it can also be from upper airway resistance syndrome, another way, which, by the way, that also increases your adrenaline, which then wakes you up. Then, of course, people who have low hormones tend to sleep poorly, especially if your progesterone is low. You tend to sleep poorly. All of these things can collude to give you a poor sleep, and that's such a critical time. Of course, so many of us have situations where we say, well, we just can't afford to sleep that much. We've got a lot of stuff going on at night. We've got a lot of stuff going on early in the morning. We're just not going to get sleep. That's a short-term solution. That's not a long-term solution. Dr. Pompa:No.

Dr. Justin:And the brain training and stress management to meditation—these things do affect the brain. the brain. I remember listening to some scientists talk about the ways in which meditation actually improves connectivity in the brain, neuroplasticity, brain cells, reduce inflammation. So, it's not just, oh, just to relax.

There's actually science around how it actually affects the brain in a positive way. You know, it's interesting. If you simply look at people's cortisol levels, as the cortisol levels go up, the brain size goes down. And so, in fact, when we were developing drugs over the many years in the lab for Alzheimer's, One of the thing that came out that was very interesting is that there is a cortisol, or it's a corticotropin releasing factor, so CRF1 receptor in the brain, in the hippocampus, and blocking this actually improved both the amyloid and the tau in the brain. In fact, the whole stress pathway is absolutely part of cognitive decline. Yes, fine to have some transient stress and then respond to it. That's great. That's what we're made to do. But as you know, this chronic stress for many, many years is damaging to your brain, it's damaging to your vessels, you get the hypertension, on and on with all these problems, poor sleep, etc. And so addressing that is very helpful. As you indicated, some form of meditation, whether it's TM, whether it's mindfulness, what have you, very helpful as well in this whole system. Getting that stress when your brain feels that stress and and your amygdala is responding to this. Part of the response is, okay, we can't deal with the brain that we have. We're going to have to downsize a little bit. You want to get rid of that as well. Then, there's targeted supplementation and there's detoxification. Then, addressing the various things that you've identified, such as mycotoxins, which can take years to reduce these things, but it's well worth it because it keeps you out of a nursing home and keeps you sharp. The most common thing we from people is, oh my gosh, my spouse is so much more engaged since he or she has been doing this.

Yeah, that's true. So, you go through all these various modalities like diet, exercise, sleep, stress reduction, brain training, which essentially is using basically, I think about, you know, crossword puzzles, Sudoku, those kinds of things. But, there's actually software that allows you to really scientifically improve your brain. It's like brainer size, like brain HQ. So you include that. And then what's really fascinating is you then start to go into how do we facilitate the brain to grow and to heal and repair? You call these trophic factors. Trophic means to grow. And so you use hormones, right? And you use estrogen, testosterone, progesterone, and then nutrients. So you replace all the missing nutrients. And the key thing like vitamin D, omega-3s, B vitamins, all these really help. and then you focus on the gut, right? You focus on fixing the gut if that's a problem. You start dealing with the infections and the inflammation causes. You start addressing the toxins, the mold. So this is all part of a functional medicine approach. And I found this incredibly effective for so many patients. And what really I sort of want to sort of talk about is what you found in the study now. You did all these things with these patients, and you did you did a follow-up to look at brain size, to look at cognitive performance on standardized testing, you looked at all the biomarkers. What were the big findings and takeaways from the study?

Yeah, I think the big takeaway from the study is that for virtually everyone, Alzheimer's and pre-Alzheimer's can be reversed. That you can reverse this problem by addressing the things that are causing it. We know now from people who have been on this since 2012, we had our first patients go on this in 2012, they are still better. This is something that was unheard of before because with a drug, you may get a little bump, but then you go right back to declining. Unfortunately, when you look out at five years, the people who went on these drugs typically are just as bad or worse than the ones who didn't go on them. So with this, you improve and then you stay improved because you're actually addressing the root cause just as you've mentioned. So I think the big takeaway was the vast majority of these people could get better. And then secondly, the few who didn't, you could see why they didn't. You could see what wasn't addressed. You could see if they stopped doing the right things. And then thirdly, we've got, as I say, the sustaining of this. Then, of course, the fourth takeaway would be that you've got to get the people to change their biochemistry. You've got to get them into that mild ketosis. You've got to make them insulin sensitive. As the metabolism goes, so goes the cognition. Of course, we now need to look at, okay, what do we need to do to make this even better, better, better? This is a wonderful start. We're seeing, we saw on average, increasing in scores of 3.89 as opposed to, for example, the drug that was just considered a success at a canabemab, no improvement, no stabilization, but in one trial at one dose only, the decline slowed by 22%. That was the exciting result.

So basically none of these drugs work, and at best they'll slow you down a little bit, so maybe you won't end up in a nursing home for six months more than you, right? It's like we're not talking about any great breakthroughs here. Everybody gets so excited, we're doing this drug and it's billions of dollars and it's so expensive and healthcare pays for it. But this kind of approach is not something that's really funded by health insurance. So it's pretty frustrating for people.

Absolutely. And then of course there's big discussions now, right now, about who is going to pay if atacanemab is now, since it's been approved, back on June 7th, who will pay? If you go in and get this drug that may slow the decline slightly. And of course, your Cleveland Clinic has come out saying that they're not going to pay for this. Medicare is still deciding. The VA has decided we will not pay for this. About $100,000 per year, $56,000 for the drug, and then additional for the infusions, for the PET scans, for the MRIs, for all the other things you need. so it's extremely expensive. And of course, the people who develop Alzheimer's spend on average $350,000 per person by the time they pass away. Much of that, of course, is for nursing homes. So it's, as you said, this is the most expensive disease. We're over $300 billion now in the United States per year because of all the lost wages. the people who are, the caregivers, the medications, the nursing homes, all these sorts of things. It's truly heartbreaking. Taking this sort of approach, whereas you indicated, you look at all these things and now you address all these things that have failed, get you back to a system that functions again, makes all the difference.

It's amazing. You did very rigorous science looking at all the standardized tests that a traditional neurologist would look at CNS vital signs. They call the Moca test, which is the Montreal Cognitive Assessment. You looked at brain training scores that are objective scores, looking at how people improve. You look at brain MRI. I mean, how do you even get something more objective than looking at someone's brain size? And you saw changes in brain size and in volume of the hippocampus, which is the memory center, which is really staggering when you think about it. So, you know, even if you're only 10% right, It's still a major breakthrough, right? And I'm wondering why do you think you haven't been able to get funding from the NIH or major Alzheimer's subgroups? What do you think that sort of resistance is that's kind of behind this? Because it just seems like this is so obvious to me. The results are there. You've got preliminary data. Why don't we just put our chips on that bet and double down? and go for it.

Yeah, it's a great point. I think that there's a system is in place. As you know, there is no place in the United States that is teaching no medical school other than yours that is teaching functional medicine to part. I actually talked to the vice chancellor of one of the greatest universities in the country in terms of medical school who said, you know, we'd like to teach this new medicine. But we can't do that until all doctors accept it. Well, of course, all doctors won't accept it until you teach it in medical school. So we're kind of stuck in this loop of, you know, let's do things the old-fashioned way. And I think it will take, I continue, you know, it'll take more trials to show that this is clearly superior. I do think in the long run it's going to be combining targeted drugs with an overall protocol. like a functional medicine protocol like this, that's going to get you the best outcomes because these targeted drugs are very good at what they do. It's just as you indicated earlier, they close one hole out of the 36 holes. So you're still, you've got a lot open. But having them for targeted things is going to be very helpful. So I'm hoping at some point that the drug companies will understand that their drugs will work better on the top bone of these. I think when that happens, things will slowly start to improve. But look what happened, Mark, with the opioid scandal. There was coercion. Because there were billions of dollars at stake, there was a whole infrastructure set up. There was coercion for doctors. Do this, make us lots of money. And to some extent, Alzheimer's currently is the new opioid scandal. There is coercion. There is an infrastructure. People are saying, well, you have to do this. You've got to do this drug. And there was a great piece a couple of days ago talking about this new drug. They were interviewing a guy who said, oh, this is a breath of fresh air. I'm giving this drug to all my patients. Oh, who are you? Well, I'm a consultant for the company. Well, okay, yes. If you're a consultant for your company and you're being paid—and by the way, Biogen has paid the Alzheimer's Association. The Alzheimer's Association, in turn, says, oh, we think it's a good drug. They've paid other foundations. This is just an unethical approach, unfortunately. and so it's going to take some time to break through that infrastructure that has been created by billions of dollars.

Well, the good news, Dale, is that you've really done the work and you've also written a number of books that I think for people listening, lay out the protocols and what to think about, what to test, how to work with your doctor, including the end of Alzheimer's, end of Alzheimer's program. And this new book, I, I sort of want to dip into a little bit. The first survivors of Alzheimer's, how patients recovered life and hope in their own words. Because, you know, we really, you know, we hear cancer survivors. We never hear of Alzheimer's survivors. So tell us about some of the stories that you found striking and what are the takeaways that you have from some of these patients.

Yeah, you know, this book was really a labor of love because it was so great when I started hearing these stories from the people and how it affects their families. For example, Julie who talked about when she first told her son her diagnosis, she had been to a neurologist and she said, I'm EPO E44, so highest risk group. Unfortunately, I have cognitive decline. Can you just at least help me stay where I am? The doctor looked at her and said, Good luck with that. What a horrible thing to say to a patient. She told her son who started crying and said, Mom, I don't want you to die. She ended up doing these various same sorts of pieces and she ended up having all a number of things. She had insulin resistance. She had inflammation initially. She's done so much better. Interestingly, she then had a little bit of a backslide, and it turned out she ended up having babesia. She had had a tick bite and had gotten rid of the Lyme but didn't realize that she had a co-infection. Now it turns out she's also got some mycotoxicity, so that's being dealt with. With each of these things, she's getting better and better. She's gone from 35th percentile on her cognitive scoring to 98th percentile. Wow. She's almost normal. Yeah. So, very, very high normal. She's doing great. In fact, she wrote a substantial part of the second book, the End of Alzheimer's Program, based on what she has been doing for her own lifestyle and diet and things like that. She's one of the seven stories. We have seven wonderful stories. Frank, a guy who moved to Mexico because he knew he wouldn't have enough money as he got demented. His doctor said, oh, you've got mild cognitive impairment. He said, There's nothing mild about this. It's ruining my life. He's done very, very well. We have Sally who actually went on a drug trial. She had a positive amyloid PET scan. She was APOE4 positive. She went on a drug trial, and as we've seen with a number of other patients, When she would get the drug, she would get much worse for a couple of weeks and then slowly improve slightly and then get almost back to where she was and then get the next injection a month later. Because remember, this stuff is antimicrobial. If you have an ongoing insult, getting rid of it is the last thing you want to do. She would get worse. Fortunately for her, after her sixth injection, she said, this is making me worse, not better. She quit. She then went on the protocol, and she's now got a perfect MOCAT score of 30. She's done great.

Dr. 30, completely normal. And what was it before?

She started at 24. So she had significant MCI. And again, you don't start going down on your MOCAT until you're fairly far along in the disease. She already had the positive amyloid scan. She already had well into MCI, the third of the four stages. She's done very, very well. Now, five years into this, she's still scoring 30 and doing really, really well. She had gotten to the point where she would forget to pick up her granddaughters at school. She writes about this. Then, when she found out, My God, I didn't pick them up. She would be just horrified. Oh, my God, I'm going to lose my granddaughters because of my cognitive problems. She ended up having a tremendous amount of mycotoxicity. actually had to get away from the source of that and go into a detox program, and she's done very, very well. So we have story after story after story of these people and how it affected their families and how much better they've done by doing the right things.

This is extraordinary, Dale, and I think that people need to take home that one, that if you even start to have symptoms, there's something you can do. More importantly, there's a lot of people who are at risk. We say there's 14 million people who are going to have Alzheimer's in a few years. How many people actually have pre-Alzheimer's or are headed that direction? Because it's tens and tens of millions, right? And this program is approach is not just for when you get it. It's actually an approach that you should do decades before you actually get any symptoms, if you're at risk, right?

Yeah, we recommend that everyone who's 45 years of age or older get a Cognoscopy, just like we know when you turn 50 you get a colonoscopy. When you hit 45, please get a Cognoscopy. That's a set of blood tests that we've been talking about. It's an online cognitive assessment, very simple, takes about 30 minutes, and then if you have symptoms already or if you're scoring poorly on the tests, it includes an MRI with volumetrics. That's it. It's simple to do. I have to say it's much more pleasant than a colonoscopy. Get that checked out and then get on appropriate prevention because as you indicated, the numbers are staggering. If you look across the spectrum, and there's a beautiful paper by Professor Christine Yaffe from UC San Francisco who showed that if you just follow serial autopsies, this is now the third leading cause of death. About 15% of people, so about 45 million Americans will die from Alzheimer's disease if we don't do something, if we don't have active prevention and early reversal, we will end up with about 15% of the population dying from this. As you indicated, already about 6 million diagnosed, heading for 14 million, but then over 10 million that are on their way to get diagnosed. So we'll end up with all people from zero to the oldest ages, about 45 million of the current currently living Americans will die from Alzheimer's if we don't get on appropriate prevention and treatment.

If you love that last video, you should check out the next one for sure on getting to the root cause of all disease.

We're not taught this in medical school, but we should be because the science.

Of health is really the future of medicine.

It's really powerful and that's what functional medicine is. And coming from your perspective, you know.