The Dementia Epidemic: What Actually Works & Why 20,000 Patient Trials Failed

One in nine Americans over the age of 65, that includes you and me, uh, is already diagnosed with dementia. To not call that a an epidemic, I think is underelling it. [music] You and I have been saying this for years, and now the data is finally catching up with us. I mean 17 trials over 20,000 patients and it says that FDA approved amaloid clearing drugs deliver no meaningful benefit and raise the risk of brain swelling and bleeding. So what does this recent confirmation mean to you? >> What it means to me I think is again a confirmation is a great word. It pretty well confirms what we have been talking about for an awful long time. even before there were drugs that uh there was this amaloid centric view of Alzheimer's disease caused by one thing the accumulation of this beta amaloid in the brain end of story and it's called the amaloid hypothesis and I think that's a great term because a hypothesis is something that we will it's an idea that we will then test and what's happened is the testing has shown that this is not the cause of Alzheimer's disease but it's a monotherapy approach getting rid of the amaloid should be presto changenjo the brain is fixed everything's good and go on about your business well the reality is because the hypothesis is flawed that getting rid of the amaloid has proven to be completely uh ineffective you just mentioned a cockrine analysis and you know for people in the field uh that is the gold standard there's nothing better this is an unbiased look at as much data that one can find to come up with an answer for a question. And the question they asked in this case was do the amaloid targeting drugs work in the treatment of Alzheimer's disease. And what they came up with was no. And as you well mentioned you know this is 20,342 patients in 17 different studies over 18 months per study looking at all the data. And there's no real benefit to using these drugs at all in the face of what you well characterize significant risk with 20 to 25% of people having brain hemorrhages and swelling uh with the statement from you know the drug manufacturer that we don't know if this is going to be a long-term problem or not. One would think just on the outside that bleeding into your brain and swelling might not be the best thing for you. Nonetheless, I mean the whole scenario under which these drugs came under FDA uh evaluation and then subsequent approval if we had time and maybe we will we can talk about how that process occurred because it's it's worrisome how that even happened. But that said, we have to ask ourselves what is upstream of the amaloid accumulation that's really at play here. And as you said in your setup, it is the activation of the brain's immune system. the inappropriate activation and persistent activation of the immune system that leads to a good brain going south. And I think that what is so empowering for our time together today is that we can control that. That so much Dr. Gundry of what you've been talking about for so many years is at play here. Meaning the metabolic issues that you know really belleaguer the human body are what is targeting these brain immune cells called microg ga to turn their backs on us and to shift to a form that is threatening. It's the same process that's underlying uh coronary artery disease uh generally heart disease uh immune dysfunction throughout the human body. And the good news that what we will certainly unpack is that our choices determine whether the immune system in the brain is friend or foe. When it's foe, when it's working against us, then it sets the stage for the destruction of our brain cells, the destruction of the connection between those brain cells called synapses and even uh disruption of the very important bloodb brain barrier. So, I think the, you know, the synopsis here is that we can give you the keys to the kingdom. And it's all about reigning in the function of our brain's immune cells by targeting their metabolism. And here's the home run. Their metabolism mirrors your body metabolism. >> Actually, just a few weeks ago, I had the honor of addressing the Alzheimer's Association here in Southern California. And uh the way I set it up and I think you explained it very well. Most of us remember 9/11 and I actually made a joke that if you don't remember 9/11, you're here at the right place at the Alzheimer's Association. But after 9/11, we began putting barriers against terrorists uh in front of important structures, airports, government buildings. And these barriers were designed to prevent a terrorist from taking a car or whatever and ramming through. And I said, "Imagine, if you will, that the barriers in your brain, such as amaloid plaques, are actually barriers to prevent terrorists access to these important structures, the neurons. And we assume that the barriers were the cause of the problem, but they're just a living example of we're trying to prevent something from getting to the brain. And you and I agree that those somethings are things that are coming from the gut like lipopolysaccharides, just to name one, like living bacteria to live name another. You're right. We've been targeting the wrong thing. We don't taking down the barriers didn't work. >> No. And in fact, it's been a couple of decades that we've uh seen the research of Dr. Rudolph Tanzy at Harvard who has characterized beta amaloid as being what we call an anti-microbial peptide, the barrier that you just referred to. In other words, it's there as a response to the threat of the terrorist, i.e. some sort of bacteria or virus. So in a very real sense uh the enemy of my enemy is my friend. We shouldn't be getting rid of the beta amalloid. That isn't the issue here. The issue is what is causing it to accumulate. And you know one very important thing that you that you raised just now is this gut brain connection. Who knew right that things from the gut can make their way through the systemic circulation and ultimately get into the brain. And I've puzzled over, okay, now that they're in the brain, why is there a threat? What do they do there? And it turns out that there are receptors on these micro gal cells that sense these products, the lipopolysaccharide that you mentioned, the LPS, or even inflammatory cytoines or particles of viruses or bacteria. that then shifts them from being supportive and nurturing and allowing us to grow new brain cells to what I call in the book the evil twin. The evil twin destroys our synapses, creates an environment that is less favorable for the neurons and destabilizes the bloodb brain barrier and this sets the stage for really the brain to ultimately decline. And you know the issue is that I think the biggest factor at play in our modern world is the metabolism of these immune cells being challenged. Normally their mitochondria are working quite efficiently cranking out that ATP that allows them to stay on our side to stay supportive and nurturing of everything going on in the brain. When the metabolism of these cells shifts away from the mitochondria, in other words, the mitochondria become less effective in producing these ATP molecules, these energy molecules. What happens is these cells shift to a different form of energy metabolism called glycolysis. And when they do so, again, they become the evil twin. And that evil twin is again an immune cell that would otherwise be very supportive. It goes around through the brain and digests away the synapses that are the connection between one brain cell and the next brain cell and really the fundamental for us to remain connected to ourselves and to each other and to the world around us. So you know that is really central to what goes on uh making the brain ultimately degenerate. And again the empowering part of this story uh is that these micro gal cells in terms of their metabolism that dictates whether they are friend or foe that metabolism mirrors our body metabolism. Things like threats to the the gut barrier that you've been so eloquent in talking about for years uh really set the stage for these cells to shift and turn their backs on us. And the really empowering good news is that we can bring things back. >> We know now I guess uh that you know our immune system was designed to defend us from from bacteria from viruses uh from other assaults. Uh years ago when the plant paradox came out, I was honored to talk at Harvard at a neurology conference and actually saw uh living pictures of what you describe that these microgal cells are literally like Pac-Man that take the dendritic processes of neurons and literally eat them away. And I mean you can watch this in real time when they sense a threat. Now I've described it in a in a slightly different way. I I look at it the neuron is the castle and these dendrites where they make connections with the synapses are forts in the hinterlands and the invaders are attacking the forts and the [clears throat] castle says, "Oh my gosh, we got to get everybody back in the fort. pull up the drawbridge and this will be our last line of defense. And so these guys have been nibbling away these dendritic processes as a as a bad method of defense. [snorts] But then we pull up the drawbridge and the poor neuron among other things stars to death and you're right can't communicate to any other neuron. >> It's all about loss of connection. But I I I want to take a step back and for your audience ask the question, why would Dr. Steven Gundry, a cardiologist who's now spending a lot of time exploring what's going on in the gut? Why would Dr. Gundry be invited to speak to a neurology uh conference? Think about that. It is because of these exact shared mechanisms that you described that yes, the gut is magically related to the brain. Who knew? I mean many years ago I wrote a book uh called Brain Maker talking about the gut brain connection and my colleagues really uh to be fair gave me a bit of a hard time because you know how could the gut for example be related to the brain or the heart or the immune system or cancer risk all of these issues that you have again so well described so you're exactly right I mean we have had this neuronal centric kind of view of the brain it's all about the neuron uh for really most of my professional career that's for sure for 40 years. That's really all the attention uh was directed at the neuron, the brain cell. And reality is the neuron is the workhorse. And what's directing the show, what's keeping things going are these microgle cells, these immune cells. really expands our view away from just thinking about immunity as a response to a threat to really more of the housekeeping uh kinds of tasks. Keeping things in tip-top shape, keeping those synapses working that you well described, keeping the neurons functional, making sure that debris is removed, making sure that that vital bloodb brain barrier is actually patent or functional. Because when any uh link in this chain gets weakened, then basically all hell breaks loose. And you know, the numbers that you quoted at the beginning of our time together today are staggering. When we recognize that right now, not in right now, 1 in nine Americans over the age of 65, that includes you and me, uh is already diagnosed with dementia. To not call that a an epidemic, I think is underelling it. It is an epidemic. And what is so incredibly valuable is for your viewers to get their arms around the fact that everything Dr. Gundry's been telling them for years of watching this podcast and writing your books is spoton as it relates to the brain. That we've got to keep our blood sugar in check. We've got to keep our waistlines in check. We've got to keep blood pressure in check. We've got to exercise, get a good night's sleep, and socialize with other people. These are the simple keys to the kingdom. There is no magic drug. And I will tell you, if there were some miraculous drug, I would have prescribed it. Uh I would have prescribed it to my own father who died of this very disease. >> Yeah. Yeah, >> but I one other point I'd like to make and well I'll make many more points in our time together is that what's really exciting for me is that we we now understand that this role of the immune system in neurodeeneration or the degeneration of the brain extends far beyond Alzheimer's disease involves Parkinson's and multi-cystemmat atrophy and fronttotemporal dementia and progressive supernuclear palsy and all of the various types of neurodeenerative conditions and Even neurodedevelopmental conditions like autism spectrum disorder and even mood disorders like uh major depressive disorder are all really now uh seen to be a representation of this activation of the immune system away from being what we call M2 supportive to being M1 destructive. And so it's throwing a very very large net. And you know, we've known for several years that metabolic issues like having elevated blood sugar significantly increases risk for having major depression, for example. What we've not recognized, but certainly need to recognize, is that being a type 2 diabetic is associated with as much as an 85% increased risk for developing Parkinson's and [clears throat] as high as a threefold increased risk for developing Alzheimer's. So this idea of this change in the brain's immune system being influenced by our metabolic state I think is now having a huge amount of traction and we're already seeing interventional trials whereby the metabolism is targeted even in existing Alzheimer's patients with really amazing uh outcomes in terms of improvement not just slowing their rate of decline but stabilization and even improvement. One study came from actually I mentioned his name already Dr. Rudolph Tanzy working with Dr. Dean Ornish, a cardiologist, published at Harvard where they took uh a group of 51 individuals who were diagnosed with Alzheimer's disease and put them on a lifestyle modification program, changing their diets, getting them to exercise, managing stress. And over the 20 weeks, 70% of these individuals either had stabilization or improvement in their cognitive function. These are people uh you know who went through a program. The side effects were lowering of their blood sugar, losing weight and you know basically improving their cardiovascular function. That was the side effects. And these weren't people taking a beta amalloid targeting drug risking themselves uh with respect to brain hemorrhage or brain swelling. So you know you can't patent that kind of intervention and you can't sell it on TV as an advertisement. And yet look what these guys did. You know I think your mission my mission is to get the word out that we all have the tools in our hands. It's just you know about guidance to to really learn how to implement these tools. That's why I wrote this book is to really let people understand that there is no magic bullet out there. Again, I wish there were. When it becomes available, you and I will both talk about it. We've dedicated ourselves to expanding the the number of tools in the toolbox. Y >> looking looking at risk benefit ratio and uh you know that's the mission here. Empowerment through knowledge is what was really what we do. >> Well, you you mentioned this throughout the book, but you and I uh are just slow learners. I mean, Hypocrates, the father of medicine, 2500 years ago, said all diseases begin in the gut. And I guess I'm a slow learner. He was right. And then we now have the tools to show why he was right. And you you spend a lot of time in the book talking about those tools and using those tools to modify without drugs with, you know, with really fairly simple steps that you can have tremendous impact. You know, our our good friend Dale Bredesen has just published a paper doing looking at very much the same thing, the lifestyle intervention. uh he makes a point which you do in the book as well that besides diet and exercise we're we're in a toxic environment. Uh whether it's pesticides, herbicides, whether it's microlastics, whether it's noise and that was actually a good point in your book that noise in itself is traumatic to the brain. So what do you do to improve things step by step simple steps that you can take to stop this process or at least well I think you can reverse it as as you think but at least stop it. I think step number one and it supersedes everything else one might do is to reframe your thinking on exactly what we are talking about to the extent that you begin to embrace the idea that you can make these changes and that they're going to be valuable because if you don't do that then nothing else matters because you won't do anything else. You know, we can talk about why sleep is important, why reigning in metabolism through dietary approaches and exercise and I might add sleep again uh are very very important. But again, step one is you got to get your arms around the fact that you are uh empowered here and the ball is in your court because until that happens, we are living our lives at the mercy of uh hoping that something is developed. And as the uh film director James Cameron once famously said, hope is not a strategy. We can hope that there's a a miracle drug. And I'm I I hope that too because that's going to help a lot of people who are really not uh able to I think embrace the idea of lifestyle change and offers up yet another tool. And and let's be clear in the new book uh I discuss where drugs may play a role. We talk about GLP1 agonist drugs. I'm not saying that's what we should be doing for one and all right now, but I am uh certainly open to drugs that are incredibly effective in terms of changing metabolism and that's really the ballpark in which we find ourselves that there may be some uh you know studies that demonstrate effectiveness. the first real interventional trial using drugs GLP-1 drugs orally semiglutide uh to target Alzheimer's really did not reach the end points that they wanted although interestingly C reactive protein a marker of inflammation uh in the intervention group was reduced by some 30% there's there's some noise there in the background I think we have to pay attention to it but that said we have seen uh incredible results with uh injectable GLP-1 agonist drugs in the treatment of uh Parkinson's disease. One study in the New England Journal of Medicine actually showed that in the group receiving a GLP1 agonist drug versus placebo, the the placebo group over the uh period of the study declined as one would expect over the couple of years, whereas the um interventional group actually stabilized or slightly improved. We've never seen that uh in Parkinson's. That's treating the fire, not just the smoke. And this is a little tangential but let me say that in Parkinson's it's reasonable to treat the smoke the tremor the rigidity gives people some functionality but underneath all that they continue to decline. So this idea of you know treating the underlying disease is is new and that is certainly not what's happening as we target beta amaloid in Alzheimer's. So the keys to the kingdom again are reigning in our metabolism. That's where sleep and exercise and a diet are so fundamentally important. The simplistics of the diet, they could we could do a deep dive, but all I really want is people to be on whatever diet for them keeps their blood sugar uh intact. Keeps their blood sugar from spiking uh over 40 if you're using a continuous glucose monitor. keeps the fasting insulin low, the A1C low, not just below the level of diab di diabetes, but low to the extent of 5.3, maybe 5.4. That's not in the normal range. That's in the ideal range as it as as for our conversation. You know, that's one of the most important things about diet. There are so many diets out there, one name or another. uh every week there's a new diet whether it's primal paleo or Atkins from the old days Mediterranean Mediterranean plus you could you can name off a hundred mind diet but I I really tried to simplify uh what the recommendations are in this book by metricizing by looking at the outcome of the diet through looking at the markers of blood sugar and insulin functionality I'd like a lot of plant a lot of color on the plate we want to have those polyphenols We want to have a lot of dietary fiber to nurture our microbiome to reduce the leakiness of the gut and that LPS from making its way to the brain. And it does. I think that we've really got to reassess the type of fats that we are consuming. Uh there is a fat that's called olive oil. My friend Dr. Steven Gundry has been talking about it for years and he's right on target as usual. Uh so dietary fat we need to stop castigating it but we need to have a bit of a discussion as to what makes for a good fat versus a bad fat especially in the the context of the brain being 70% fat. We've got to make build a brain make a brain from the good fats that we are consuming. We have a discussion about the omega-3s and a discussion about protein as well. But the mission here is to simplify. The mission here is to really recognize that the gut is playing a huge role and that we've got to reign in metabolism through our dietary approaches and then move on to recognizing that metabolism, here's the new headline, is highly influenced by the quantity and quality of the sleep that we get. Well, how would you know? Well, I guess I got four hours of sleep last night. I didn't go to bed until 2 in the morning or whatever it may be. Okay, you would know that. But if you think you're sleeping eight hours a night, you might not be. You might be uh nearly waking up or actually waking up several times. And beyond that, we've got to understand the quality of sleep. Are you getting enough deep sleep, for example, to activate the brain's cleanup system called the glimpmphatic system, which we've just learned is also activated by movement during the day. But we've got to understand this. And you know, it was only just a few years ago when the only way we would know that was by undergoing a sleep study in a laboratory with a bunch of wires connected to your skull and an EKG monitor and a pulse oximter and somebody watching with a camera all night. >> They tell you go to sleep. >> Yeah. And go to sleep. But that we're watching every move. I actually underwent one because I was telling everybody back in the day, you should get one because we need to understand your sleep. So I I underwent one and before I went to sleep, the technician who was watching me uh was telling me this horrendous story. I don't want to go through it, but it was very destabilizing for my sleep. Plus, you're in a a lab. But anyway, these days, you can wear your Apple Watch, your Whoop, your Aura Ring, whatever it may be, and really get wonderful metrics uh as it relates to not only the quantity of your sleep, but I think as important, the quality. How much RAM are you getting? What was your latency? What is your heart rate variability during sleep? Which is an indication of the activation activity of your parasympathetic nervous system, the rest and digest part of your nervous system. When you're always in sympathetic overload, it increases your cortisol production. That does what? It damages and threatens your microbiome. Leads to increased gut permeability. And that is bad for your body. And yes, the brain is part of your body and your micro gal cells. getting back to our original topic can sense that and when they sense that they shift from becoming supportive to being destructive. So you know those are are the fundamentals and I will say that I wanted to pave the way for uh the idea that a uh there's some really cool things coming down the pike that aren't really readily available yet. But um you know science is really taking a leap forward in this idea that the brain's immune system holds the keys to the kingdom. Uh and b that you know we're going to remain open to that and I I presented some really forwardthinking ideas in the book you know based upon what some really cool guys and girls are doing uh research-wise that I think uh in the short term are going to be available soon. Some of which is even available right now. things as uh seemingly out there as flashing a light in your eyes at 40 hertz. I mean uh you know at first blush you're thinking yeah you know what are Gundry and Pearl Mutter smoking now flashing a light how could that be good for your brain? Well it turns out that Dr. Leeway Sai at the Massachusetts Institute of Technology, that's MIT, uh has done incredible research showing that light at that specific frequency, first in rodents and now in humans and now in humans with Alzheimer's disease is dramatic in terms of its effects on the brain's immune system. Why it happens, I don't know. I mean, what Dr. Aliway Sai has come up with is that it restores a background frequency called gamma oscillation which is a normal beautiful syosoidal kind of wave background music in the brain if you will that keeps these immune cells in check and doing good things. You know, you mentioned uh in the book about microtubules and I I bring it up because you talk you have a whole chapter on exciting new advances like flashing lights and you didn't mention uh transcranial ultrasound and I just thought I'd throw it out there because the theory is that this will actually promote microtubial growth. Um what say you? Interestingly, the the latest news on transcranial ultrasound, which of course came out after I submitted my manuscript, isn't that as did the the cockrine analysis uh is that uh it is being looked upon right in line with what I just mentioned with the 40 Hz light. So transcranial has become uh looking like a powerful tool to reestablish this beautiful background music this gamma oscillation which will allow these microgle cells to reconvert back to being uh supportive and as you well mentioned support the function and formation of microtubules. So microtubules uh are the way uh interestingly let me just talk about one aspect of what they do. uh they actually allow the transfer from one cell to the next of functional healthy mitochondria. Can you imagine that? That one brain cell finds that its neighbor has deficiencies in the mitochondria and says, "Hey, I'll send you a few or however many you need through these microtubules." And where the story becomes really interesting is because the maintenance of the microtubules uh is the task of a specific protein in the brain called tow 217. The function of TA 217 is to keep those microtubules functioning. When we have I love this story. It's really it just floats the boat. When we have metabolic issues like elevated blood sugar, insulin resistance or inflammation in the body, what happens is that this towel protein becomes phosphorolated. That becomes something called ptow phosphorolated tow 217 and that is an indication then that the microtubules are not working as effectively. It turns out that nowadays this is one of you can measure it in the blood and you can do that without a prescription. We talk about it in the book and nowadays this has become the darling of laboratory blood analysis for Alzheimer's risk and even the progression or lack thereof of existing Alzheimer's disease. We talk about uh the idea that you can go to your local laboratory even without a prescription now and say I would like to have my pow 217 measured and uh you know we put in the book what are good levels of pal 217 I just had mine measured it was less than 0.1 which is a good thing uh and meaning that uh my metabolics are intact to the extent that I am not threatening to change my functional TW protein into phosphorolated tile protein. That's what this test means. Therefore, my risk right now for developing Alzheimer's is seemingly low. It all comes together [clears throat] when we look uh even through the lens of these microtubules. When microtubules are threatened and not working appropriately, it is associated with shifting our brain's immune cells, these micro gal cells away from being friendly to being threatening, away from what we describe, well, what has been described not just by me, the M2 configuration into the threatening M1 configuration. I think women really ought to know that at least in Alzheimer's, they are not the stronger sex. They're by far the stronger sex in most most things, as my wife reminds me all the time and my two daughters, but women are far more susceptible to Alzheimer's than men. And I think that does not get enough clarity clarification from from all of us. Um any thoughts on that? >> Well, actually I dedicated a section in the book to that. I think uh most importantly is the fact that women are represent twothirds of the Alzheimer's patients here in America and I put in the book a comment because I think it's very valuable that women have not been the subject of research to answer the question why. And you know books have been written Dr. Lisa Musonei wrote a wonderful book, XX Factor or XX Syndrome, I forget what the title was, but her name is Lisa Musonei. >> Yeah. >> Uh wrote this beautiful book and it unpacks a lot of uh explanations. From my perspective, what I really dwelled on in uh Brain Defenders is the idea that when this manifestation begins, uh it really is around the permenopausal time. And what happens during permenopausal time is that levels of a particular hormone estradiol which is E2 a form of estrogen plummets dramatically. And when estradiol plummets drops dramatically it marks the synapses with a certain type of protein called complement protein. And when these synapses or connections between brain cells are tagged with complement protein then the microgal cells see them uh as prime for digestion. So this tagging of the synapses the connection of one neuron to the next neuron through their dendrites. Uh when they are tagged because estradiol levels plummet it sends at what's called an eat me signal to the microg ga. So uh interestingly uh again what's happening is that we are seeing a very powerful connection here through the hormone system uh of activation of these micro gleal cells such that I came out very much in favor of hormone replacement therapy uh as it relates to a a technique of keeping this particular mechanism from happening. You know there are other aspects of hormones that I think are very valuable acting as trophic hormones or nurturing hormones in the brain as well. But you know I think when my mission was to really uh vet where is this brain immune system playing a role and how are these various inroads being explained through the lens of these microgle cells and through that lens we get a great understanding about what's going on in the female brain. Uh there there are other uh things that have come to light really very recently. One a researcher Dr. Sarah Marzy at the Marzy Institute uh in the uh in England uh neuroscience institute has really identified that there are different epigenetic markers in neurons uh in men versus women. Uh some of which are induced uh these epigenetic markers by uh not just gender but we induce these epigenetic markers in other words uh changing of gene expression uh in men and women through toxic exposure for example. Yeah, >> that and that's varies depending upon the part of the brain that uh is involved. Different epigenetic changes happen for example in the area of the brain that makes dopamine for the motor system that area then being involved as she identified uh so eloquently and when she describes it in Parkinson's. So, we're really in a very uh exciting time uh in determining what it is that activates these immune cells to then digest away neurons and digest away synapses. And you know, as it relates again back to your question, the the gender differences, my my bullet points would be number one that women need more attention being twothirds of Alzheimer's patients and and I think uh research needs to be more directed to your question and secondly that uh hormones I think are playing a pivotal role and now we understand why. >> In your book you make a uh and thank you for doing this. Um there is probably a window of opportunity in pmenopause and menopause to start hormone replacement and it'll help and I totally agree with that. But uh you make a good point and I totally agree with you that if you kind of miss that window of opportunity and the European data would suggest that it's 3 to 5 years. If you miss that window, then you kind of are playing Russian roulette. And and sadly, I see that frequently with my patients with increased risk of cancer, increased cardiovascular disease risk, even increased risk of bone loss. And you point this out and and thank you for doing that because sometimes I feel like I'm not completely on the bandwagon that hormone replacement uh started at age 70 is a really good idea. >> I think uh it gets to timing. Uh actually Dr. Bone, I mentioned her just a moment ago, is at present carrying out an interventional trial and again what you said is so on point that it is all about timing. So yeah, I had a thought this morning. I was thinking, you know, we had dinner with a couple last night and uh people that we've been friends with for many, many years and one of the uh individuals is has developed Alzheimer's and uh you know ultimately the the tragic part was that she's aware of the fact that her mother ended up with the same situation ended up in a memory care clinic or or center. And I thought, what a strange thing to call it, a memory care center, because what I'm doing right now is memory care is really before there's an issue, preventive care. Uh that's what memory care should should be all about. And that is to say, getting back to our our current point, uh I mentioned in the book, and no, I didn't hold back. I said, so are you to make it very clear where I stand on hormone replacement therapy. I am in favor of I mean I think the whole idea of the breast cancer risk etc. You and I both know that that data was was really very flawed and really derailed the medicine and healthc care away from the notion of of of hormone replacement being you know having some possible positive aspects which I I believe it does. So, uh, you know, the idea of of getting back to that memory care, I I want memory care to start in our 40s and 50s when we have a memory and we want to care for that memory because that is when the seeds of our metabolic mayhem begin in our 40s and 50s when the seeds for Alzheimer's are planted, not when we are becoming forgetful. So it's very heartening for me to see that there is now a journal of prevention of Alzheimer's. that is uh it's breathtaking that there's a journal a peer-reviewed journal dedicated to the idea of preventing Alzheimer's disease which is you know a fundamental shift in just the whole uh approach of medicine and health care here in America certainly you know call it like it is it's not health care it's illness care we don't do anything for people until they are ill in my world it's until they develop a neurodeenerative condition then we hope we're going to do something when it's really you fourth and long. There's three three seconds left on the clock. No, I I think the time uh as John Kennedy said in his inaugural address, the time to fix the roof is when the sun is shining. And that's that's my message. And uh you know, I I'll keep repeating this message until it it takes hold. >> You kind of finish up um with this. We talk about all this doom and gloom. Uh but there is, you know, honest hope and uh you lay it out. [clears throat] And does it take some work? Yes. Uh >> it does. And is it worth it? You bet. >> Yeah. You know, as I tell my patients, you're probably going to hate me for about 6 weeks and you're probably going to start liking me after that. And I think it's the same message here. You you got to work at this. Uh but the alternative is as you and I know is disastrous. >> Call it like it is. You know our options once it's happened once that diagnosis is made are slim and none. I mean uh you know I I as you would have expected put a section in the book dedicated to our friend Dr. Dale Bredesen because as you well know he is developing uh an interventional approach that is showing success in in some patients >> by targeting these triggers that force our microgle cells away from being friend to being foe. It's a fundamental of this book. It's a fundamental I think of where the science is going now which is very heartening. I mean we're seeing researchers do micro galal transplants into the brains of humans not just laboratory animals doing uh mitochondrial transplants uh into humans not just rodents. So this is very very exciting. It's very exciting time when now we focus on this idea that uh this is you know really where the money is and you know for me the fact that this book is coming out now and is is already going to be published in 16 countries around the world you know at the same time it's published here in America normally as you know you get your French version and your Spanish version you know a year later when they say yeah it did pretty well in America right >> this is getting out early across the world. And I couldn't be happier because this is is so important not just for the general public to appreciate, but also I think to validate the the researchers that are doing this work around the world that yeah, you guys are on the right track and it's it's all about the simple stuff. It's all about eating right, getting exercise, socializing. I mean, you know, the blue zones told us a few important uh levers to pull. And I think that the the idea of the fact that people who are socially connected have a lower risk of heart disease, a lower risk of cancer, and yes, a lower risk of developing Alzheimer's disease. The question is why? Well, interestingly, we can deconstruct and say, well, socialization is associated with better metabolic health. We know that lower levels of inflammatory cytoines in the blood that's been demonstrated as well. Better insulin functionality. But interestingly, when we are together with other people, even virtually, even what's going on between you and me right now, you create higher levels of the love hormone in your body called oxytocin. I mean, just because you and I are friends and we're hanging out together, more oxytocin in our in our bloodstream and it makes its way to the brain. Uh, and that oxytocin, well, you know, that's originally where it came from anyway, targets our micro gal cells. Our micro gal cells have oxytocin receptors on their surfaces. When that uh receptor is stimulated by higher levels of oxytocin, they stay in their supportive, loving, nurturing role. And you wonder, okay, I know I'm supposed to socialize. I'm supposed to play bridge with people or botchi ball or whatever it is, you know, meet in the public square and that's good for my body, good for my brain. uh but now if you have to deconstruct it and you need a mechanism that's very powerful uh oxytocin and in fact there's been an interventional trial now that showed some interesting findings some of which were positive very small trial of only five Alzheimer's but gave them intraasal sprays of oxytocin uh so I think um it's it's there for the asking you can do intraasal spray of oxtocin if you choose but you know what uh maybe get off the internet and stop doom scrolling. You go outside and talk to your neighbor. That's powerful therapy. Who knew? >> Well, that's why I tell everybody to get a dog. Uh because it forces you go walking twice twice a day and you will more than likely run into another dog walker and your dogs will have to socialize and it'll force you to socialize. So, just another reason. Plus, your dogs bring a great microbiome to you. And who knows, maybe socialization, you and I, well, we can't do it here, but among groups of people, we exchange bacteria all the time. >> I seem to recall that you and I may have talked about this once before. Uh I think that was the last conversation I had about this, that that's actually good for us. Certainly having pets, you know, it uh it helps stabilize immune function and resets immune function. We know that kids who grow up with pets or living on a farm are exposed to dirt and and germs, germs in a good sense. Who knew? And their risk for food allergies etc. and attopic dermatitis, etc. remarkably reduced. So, >> so you're right. You know, I I think we're coming into a time when we are really recontextualizing the whole notion of the immune system again. you know, moving away from it just being involved as a response element against being threatened uh to being, you know, really deeply involved in maintenance and nurturing and keeping things functional. And there's a new term uh that is gaining a lot of traction that marries uh the immune system to our metabolic uh functionality and it's called, oddly enough, imunomabolism. And that has become my watch word, immunomabolism. The idea that our metabolism is so deeply intertwined with the regulation and activity of our immune system, it relates diabetes, hypertension, obesity, uh hyper lipidmia to the functionality of the immune system. And now we get it. We understand this relationship between metabolic issues in coronary artery disease and risk for cancer and in and neurodeenerative conditions as well because of how these metabolic issues are interpreted and reprogram in our case our discussion today the micro gal cells nurturing and supportive of even the very synapses that connect one neuron to the next uh to shifting because of our metabolic issues. to being the evil twin as we talked about in the book. So the tools are very straightforward and the tools are now totally validated and allow us to understand the associations between metabolic issues and brain degeneration. I mentioned those relationships earlier and now you know we've connected some very important dots. We're getting the corner pieces of our jigsaw puzzle put in place now. The rest of the pieces now are gonna come be put in pretty easily. Uh but most importantly, these are tools as I've said a couple times today one uh in our time together. These are keys to the kingdom. The fundamental message I think I'd like to give to your viewers is don't wait. Don't wait. Don't be under this misguided uh ideology that you can live your life come what may and that modern science and medicine is going to have some miracle magic bullet uh to help you through this. We don't have a way of cleaning out your coronary arteries once they've become significantly narrowed. I wish we did. We don't have a way of uh uh generally available of really putting your brain back on track. So it's all about prevention. It's all about metabolism and through this wonderful new term imunomabolism, the relationship of our metabolic health that is dictated by our choices, the relationship to the brain's immune system, the microglea being supportive or destructive. And yes, uh like your patients who hate you for the first six weeks until the things things turn around. Yeah, I'm not saying that people are going to, you know, wonderfully embrace these dietary changes or my call for exercise or getting to bed earlier and turning off the TV and making the room colder. All of these things may not, you know, sit well with everybody. But uh by all means it's it's a better choice uh than asking yourself what am I going to do now when I've come back from the doctor's office and she has told me that I am suffering from mild cognitive impairment MCI which is a harbinger for the next diagnosis which is full-blown Alzheimer's disease. It doesn't have to happen. I am pleading with your audience. >> No, you're absolutely right. Getting back to Hypocrates, all disease begins in the gut. I have a patient who's a Sanskrit scholar and we were talking about this and he said, you know, I'm going to go back because the Buddha and Hypocrates were contemporaries and he came back and he says, you're not going to believe this, but the Buddha said enlightenment comes from the intestines and I'd like to keep this enlightened. So, I think if we can [clears throat] take care of our intestines and our microbiome, uh, we can keep keep our brain in pretty dog on good shape. You bring up again the oral microbiome and the oral cavity is so so important uh, in all of this. And maybe before we go, uh, should we brush our teeth? Should we floss? Uh, or who cares about all that? You know, our discussion of the gut uh absolutely needs to include the mouth uh because it's all the digestive system. It begins at the lips >> and and makes its way all the way through. And I mean all the way through. And uh I I think there's this sense that we need to sterilize our mouths because of germs. >> Yeah. And you know, I I think that we've got to recognize that the oral microbiome, those organisms that live in the mouth, are are there to do good things uh to keep the mouth healthy uh and have dramatic systemic effects. In other words, throughout the body, including the brain, we can uh look at one mechanism where the oral bacteria do good things. They convert nitrates in our food into nitrite. uh we eat nitraterich foods like beets for example and then these wonderful bacteria are there to serve us and convert that into nitrite that forms the basis by which our bodies are able to manufacture nitric oxide nitric oxide or N just say yes to no uh nitric oxide is very important we know uh for allowing our blood vessels to relax to get good blood supply throughout the body and yes good blood supply to the brain but I think a less known uh and equally important role of nitric oxide is to enhance how insulin does its job. Who knew that nitric oxide was really fundamentally important for the function of insulin uh throughout the body? So these are good things that our oral microbiome does. One wonders why there is such a significant increased risk for both type 2 diabetes, a metabolic issue, and elevated blood pressure, a metabolic issue. both of which threaten the brain's immune system uh in people who routinely use antibacterial mouthwashes. >> So uh interestingly both of these studies uh demonstrated that and you know this uh idea that we've got to be killing 99% of germs. That's what the commercials will tell us. That's a good thing because we might get bad breath uh hattosis give it a name and that's going to be very offensive to ourselves and to others is we need to rethink that. So I I really welcome the idea that this idea has come to light and number two that we are seeing the development of products that nurture the the oral microbiome various toothpastes uh that are designed to both strengthen our teeth to reduce our exposure to fluoride reduce our exposure to fluoride and nurture the oral microbiome. So, uh, you know, I'm really welcoming this new idea that these bacteria are not just there to be destroyed by the next time we, you know, we're in the bathroom and we see the pump thing and the little cups and off we go. It's a habit that is associated with significant risk to our metabolic state, metabolic health, and therefore to the function of the brain's immune system. It seems like a long way off, doesn't it? the idea and I talk about this in brain defenders that sterilizing your mouth with uh these mouthwash preparations is bad for the brain. Uh it's something we we need to rethink. Now uh that said, you mentioned flossing and brushing and uh what I think is really very handy and important and I use a a water flosser. I use a water pick and what what's great is, you know, they mount now make them USB rechargeable. you stick it in your in your luggage uh and then you have it when you when you travel which you should I think this is a very valuable tool because we really do need good oral health that doesn't include sterilizing the mouth it means perodontal care uh it means brushing twice a day using a water flosser uh and uh uh using dental floss if you so choose I think it's very important because when we get perodonal disease then we can have overgrowth of certain bacterial species that are bad for the body that can increase inflammation throughout the body and can even make their way to the brain. What won't be on the quiz is the name of one particular type of bacterium called prooonus gingivalis. uh but you know the idea that we can uh see this bacterium or fragments of the bacterium that still have biological activity in the brain at higher levels in Alzheimer's patients provides an important clue that periodontal disease may be playing a role. We certainly see research that shows an association between periodontal disease and inflammation throughout the body as well as a risk for Alzheimer's disease. You might believe this, but most people wouldn't. Um, 21 years ago, I gave a paper at the American Heart Association. I made people uh floss uh every other day and looked at their HSCP, highly sensitive CRP, a good marker of generalized inflammation. Why did I choose every other day? I hate to floss. Uh, my wife flosses twice a day. She's a nut. get get a water flosser and and just travel with it. >> But it turns out that if I could get people to floss every other day, their CRPS dropped dramatically and the more they flossed, the lower it went. And that was literally 25 years ago. >> I can only imagine uh how your colleagues must have responded to that presentation. I mean, I know what it's like. I I have been there giving these talks uh you know about the things that you and I know are important and uh afterwards you know people just nodding their heads and I I didn't say back then just wait uh but I knew that the research was going to ultimately make their way to their journals and it has as you've seen in cardiology journals and certainly neurology journals uh it's really quite breathtaking that uh even in the the most wellrespected mainstream neurology journal We're seeing, you know, indications of metabolism, its effect on the brain, uh even even diet. Uh even in JAMAMA, there was a study last year called the Pointer study. And the Pointer study looked at uh 20,111 uh individuals and followed them uh for 12.7 years. And it it uh was an interventional trial. What they did with these uh folks was they had two groups uh and they they followed these uh individuals uh and actually it was it was followed them for two years my mistake but again 20,000 people they had two groups. One group was given a dietary intervention, lifestyle intervention in terms of physical activity and stress alleviation etc and met over the 2-year period not 12.7 either virtually or uh real time uh counselors to guide them through. That was one half of the group and these are people in their late 60s with metabolic issues already uh insulin resistance etc overweight so at great risk right uh in whom you would expect cognitive decline over a 2-year period. The other group got the same information but had only I think three interventions or meetings with people over the uh each year for two years. a total of six versus I think 34 or 36 interventions. So what did they find? The group that had the very vigorous counseling to work through diet and lifestyle etc. They didn't stabilize their cognitive decline. They actually improved they improved their cognitive function during the end of the two-year trial. But what about the group that just got basically got the information a little pat on the back a couple of times a year? What happened to them? They dramatically improved as well. That's the part of the pointer study that doesn't really get as much attention, but the point is these people were just basically given information and their cognitive function should have declined, but it improved. It shows that these are very powerful inroads to better brain health, better brain function. Number one, and number two, it says that you, Dr. Steven Gumpy, are on track doing the right thing. even though it was 25 years ago and your colleagues were nodding their heads for you saying floss every other day. Uh so it's it it validates this idea that we've been putting forth for decades that guess what Hypocrates was on to something. Buddha was on to something that lifestyle choices are hugely important as it relates to your general health and as it relates to your brain health. And again we are the architects of our brain's destiny. That's job one is to embrace that and then hopefully the rest of what we've talked about today, those things are going to fall into place. >> Yeah. And and look, if your brain defenders are, you know, right there and all you got to do is read the book and he doesn't have to call you every other day to read the book like you just pointed out pointed out. Uh that's why this is so important and I wanted to have you on. Uh before I let you go, I like to have an audience question. And and we've got from Anon on YouTube. >> My doctor mentioned some of the new Alzheimer's drugs that are getting a lot of attention. Are they worth it? That's a great question. And uh recently I have two patients who are very educated individuals. One is in their late 70s, one's in their early 80s who have recently been diagnosed with Alzheimer's disease. both carry a single copy of the Appleoe E4 and we didn't talk about that today but we have in the past and they've decided to get this exciting new Alzheimer's drug. I've counseledled them. Uh how would you answer this question and how would you counsel my patients? Well, first I would offer up the disclaimer that I'm not their doctor, but I would say if a drug works and it's not that risky, I would absolutely take it. These drugs carry a great risk and do not work. And I would say the simplest thing would be to Google cockrine amaloid drugs and you'll get your answer because what the cockrine analysis uh found was that the drugs the term they used in terms of describing their effectiveness was trivial quote unquote. I didn't make that up. and they described the real clear and present danger of using these drugs and not to mention $40,000 a year in expense though it's covered now which is makes that Medicare is covering. Uh I had this discussion with the uh director of Medicare and Medicaid Dr. Memed Oz several weeks ago and asked why is Medicare paying for these drugs that are ineffective as per the Cochran analysis. So um the the answer to the question is that if if they were my patients, I would absolutely recommend that they steer clear of these drugs with full understanding that Dr. Pruter is would absolutely be in favor of a drug intervention if it were safe and it worked. Let me add one more thing because I think it's desperately important for these individuals that there's a a warning on the label of these drugs that they should not be used in people carrying the APOE4 alil. So the idea that they're both carers of APOE4 AIL and they're going to receive this drug is very worrisome. They are at much much higher risk for brain hemorrhage if they're exposed to these drugs. uh it's right there in uh the information about this drug that they are absolutely contraindicated meaning they should not be used in anyone carrying the APOE4 alil that was not known at the beginning of the use of these drugs uh until somebody did a stratified study to try to figure out who are these people that are at such high risk for brain hemorrhage and it turns out it's the APOE4 carriers >> again uh you've given in the book a lot of honest hope for people and I think that the takeaway particularly with this question is these drugs are not the honest hope um there are far better ways and you're right prevention it's such an ugly word but it's it's how we how you stop this >> as you mentioned ApoE E4 which is a risk uh multiplier for Alzheimer's the pointer study that I mentioned a a a little moment ago about you know over the two years people who had the very vigorous intervention or even just got the information didn't really have the interaction that included APOE4 people who improved so it's a real testament to the power of these seemingly simple uh lifestyle interventions to really write the ship and really you know redirect uh the brain's destiny so I would encourage those individuals and anyone who's you been able to listen to us today uh that even carrying the APOE4 AI is a predisposition. It is not a determinant. It is no way a determinant for getting Alzheimer's. >> You know, I got interested in the ApoE4 because a lot of my coronary artery disease patients carried it and I go, "What what's with that?" Um, so but it is not a a determinant. In fact, most people who get Alzheimer's aren't carrying that al. >> That's right. I mean APOE4 uh you know represents about 23% of Americans will carry at least one copy of the APOE4 alil and so that's that's right and uh and interesting getting back to our beta amaloid discussion 75% of people who have a lot of beta amaloid in their brains do not develop dementia so the idea that this is the cause of Alzheimer's uh is really quite uh unfounded and the idea of targeting it then for therapy for the reasons that we've discussed really makes no sense. So again where we will see wonderful developments is in the idea of imunomabolism and I am open to the idea that maybe there will be a time for using a GLP-1 an ompic like drug uh in the treatment of Alzheimer's disease in the future. I I really will keep the door open because you know we have to again look at risk benefit ratio and we know what the risks are uh at least some of them. We don't know fully what the risks are. That'll play itself out over the next few years. But face it, Alzheimer's, which has been kind of thematic of our conversation today, is pretty much a fatal condition. May represent about the third leading cause of death amongst uh adults uh in America today. And we don't normally think about it like that. Well, you know, this person's in an institution now because he or she is having cognitive issues, but it causes people to die. >> And uh therefore, the idea that there could be a drug intervention like using a GLP1 or who knows what else may be developed with a low-risk profile that could help stabilize or improve the situation. I will keep you posted. I will absolutely keep you posted and you know do the outreach on social media and and all the things because I think people need to keep their finger on the pulse of of these developments.