Alzheimer's Disease: The EARLY WARNING SIGNS & How To Reverse It | Richard Johnson & Dale Bredesen

Alzheimer's disease right now people don't think they know what causes it we don't think it's at all reversible some people don't even know what the early signs look like what say you Dale bredesen to that assertation well first of all let's put it in perspective over a million people have died from covid-19 and about 45 million of the currently living Americans will die of Alzheimer's disease so it dwarfs the covid-19 pandemic it's just a little slower as you know but the reality is we're told all the time there's you know we don't know what causes it there's nothing you can do about it we published a trial just a few months ago in the Journal of Alzheimer's disease in which 84 percent of the people actually got better so we understand it don't rush past that 84 of people actually had a reversal of symptoms a reversal of cognitive decline which we were the first to publish way back in 2014 and then we finally got were allowed to do the trial tremendous results and we not only saw are improvements in their cognitive testing but we also saw improvements in their MRIs so they actually had larger gray matter volumes and their hippocampal volumes which decline even with normal aging declined less than with even normal aging so this has not been widely recognized sorry that was going to skim over my brain for a second yeah so with the protocol that we're going to go into here people decline less than normal aging so forget the fact that they're there because they have early signs of dementia but they're you can actually slow even normal aging down yes okay so um Richard we'll get into I think the punch line that you call the switch which is a metabolic pathway that's really fascinating it's been coming up a lot in my life recently but first just to orient people to alzheimer's I know a lot of people are going to be coming to this video because they're terrified of it yeah they may have already been touched by it they have somebody in their life so speaking for myself my wife's grandmother died of Alzheimer's it is terrifying up close and the thought of like oh hey I forgot where my keys are do I have Alzheimer's you know what I mean like Orient people around that what are realistic early signs that people can look out for and then we'll dive into how we start undoing this how we can reverse that Trend yeah yeah so the reality is my generation uh the old-timers now is the last generation that should fear Alzheimer's it is literally becoming optional and here's why I say that if everybody as they get to 40 to 45 years of age or or so would simply get evaluated and get on active prevention then we could prevent this in nearly all people what does evaluation look like and the evaluation looks like three things so what we call a cognoscopy just like we all know right when you turn 50 what do you get you get a colonoscopy could be well when you're 45 40 to 45 area you should get a cognoscopy and that's three things number one a series of blood tests and they're going to be related to what Rick's expertise what's happening with your glucose and your fructose what's happening with your inflammatory Pathways all the things that Rick's research touches on fits beautifully with our theory of what's driving Alzheimer's disease so you get really fast breakdown for us what what would be a short list of things that we're going to look for In The Blood what do we care about well you know from my standpoint it would be things like insulin resistance uh measuring uh your plasma glucose or your fasting glucose level and your a thing called the Homa test which looks for insulin resistance um we'd be looking for features of metabolic syndrome uh you know do you have fatty liver do you have like all of this stuff is Downstream of glucose right well no they kind of go together with the glucose I wouldn't say they're Downstream I would say they're all occurring at the same time so features of metabolic syndrome which is obesity diabetes insulin resistance all these are risk factors for Alzheimer's um and uh and diet there's certain diet foods you know so food's very high in sugar are associated with an increased risk for Alzheimer's I'm not saying that you can't eat sugar I don't want to demonize it but um I do well so I'm curious why don't you want to be demonized sugar well I mean you know so it's true that sugar is probably we'd probably do better without it but um so many people uh you know there's so many foods that have sugar it's very hard to completely eliminate it from the diet so the practicality of unless you go like on a keto diet it may be hard to actually not eat some sugar so so it's really uh excessive sugar that's the biggest problem I mean like soft drinks yes we we can demonize soft drinks I agree with you people should not be drinking soft drinks but um you know uh you know it's very hard to you know even vegetables have will have some sugar in them and um you know so I I'm not saying that you shouldn't eat any sugar but but sugar and high fructose corn syrup are two major culprits that probably have a role in the cause of Alzheimer's okay I want to push on something that um I said which is that this is quote-unquote Downstream of glucose so Downstream may not be the right word but everything that you've listed to my Layman's understanding is going to be directly related to the amount of glucose that you consume and you're being very delicate which may be the Y stance maybe I'm the fool in this discussion but all of this stuff is going to be related to the amount of glucose that you're in taking to to my estimation is that an uncomfortable assertion no I think you're right actually I'm going to agree with you that um so there's there's a couple things the first thing is that yes obesity diabetes metabolic syndrome these are all risk factors for Alzheimer's when we get to diet sugar and high fructose corn syrup are clearly risk factors for Alzheimer's but so are carbs and so are so is glucose but carbs and glucose to my Layman's brain are one and the same if I eat carbs I'm going to minus fiber I'm going to have a glucose response in the blood and as somebody who wears a continuous glucose monitor a lot I am startled by things like carrots that will Spike my blood sugar as if I've eaten maybe not a donut but it's kind of it's scary how close the response is well you're right there's a range with carbs you with some carbs you know especially if they have a lot of fiber they don't raise the glucose as much if you have a glucose monitor versus a donut and so there is this kind of scale so the the ones the foods that particularly Drive glucose up in the blood are things like bread rice potatoes cereal you know potato chips near the top and anything that raises the glucose up anything that raises that glucose up will um get you into trouble according to our work on uh that could increase your risk for Alzheimer's okay so going back to the cognoscopy so we've got the blood work just went into some detail I think you said there were three things so that was one what are the other two and then the blood work you also want to look at inflammatory status so that what do you check for yeah check for hscrp hscrp I've never heard of it so that's high sensitivity C-reactive protein this is a pentameric protein five of them together that come out of your liver when you have exposure to various pathogens and immunological things so that's critical and in fact if you look at Alzheimer's as a disease what is it what is Alzheimer's you know it's just a name the the big finding is it is related to two major things number one is your innate immune system so this is the evolutionarily older part of your immune system that is a relatively non-specific phenomenon where it's saying something's wrong things are bad I've got to go into in an inflammatory process and ultimately hand off to the Adaptive system that now is more specific these are where the toll-like receptors and things like that come into play it's recognizing something's wrong and amyloid is part of that so the stuff that collects in your brain over the years when you get Alzheimer's is there because you are responding to insults and then the denominator of this is energetics so as your energy is dropping again coming back to the the fructose story which is why it fits so well with Rick's research you're coming back to that and it's cerebral blood flow and it's your oxygenation which is why people who have sleep apnea are at increased risk these are things I'm checking for in the cognosis exactly so you're looking at these pieces so you want to know your pathogen status is your oral microbiome full of P gingivalis which is a specific bacterium which gets into your brain by the way and your brain responds to that insult by making what's looked years down the road is Alzheimer's disease so it's those two big issues we want to know so we want to know your inflammatory status we want to know your vascular status which is why standard lipid panels things like that that's the cognosity that's part one The Blood Part Two is simple online cognitive assessment you can do that in about 25 minutes and it's going to test your memory your executive function your processing speed things like that two-thirds of the people who are heading for Alzheimer's the first thing that goes is new memory so it's laying down of memory as you know people will say uh you know hey where are we going tomorrow oh we're going to you know and and Jody's and then 10 minutes later they'll say hey where are we going tomorrow and they're like yeah we're going to Aunt Jodi's as I told you 10 minutes ago that's and that's the kind of common early thing but then there's we call that the amnestic presentation about one-third of people present with the non amnestic presentation and that's typically executive function planning problems with calculating having trouble figuring out a tip for the first time things like that having trouble working your iPhone or a new iPad or things like that these are all kind of typical of the non-amnistic presentation these are more by the way more parietal lobe functions instead of the usual temporal lobe functions which are more on the on the amnestic side so those are the things that typically come up and you can pick those up early with an online cognitive assessment and then the third part is MRI with volumetrics you want to if you have symptoms or if you're doing poorly on the testing then you want to make sure to include an MRI and not just a classical MRI you want to make sure to get volumetrics so you're looking at the size of your temporal lobe the size of your hippocampus the size of your parietal lobe how does it match up with other people of your age okay so there are predictable shrinkage for lack of a better word that we would expect to see in certain regions of the brain based on your age and so if you see something that's outpacing your age then now we've got a problem exactly okay so I would like to add something here so um you know when he talks about the cognoscopy when Dale does um I I can point out how this sort of fits in with Alzheimer's in general so you know originally when people think about Alzheimer's they think of amyloid plaques they think of these Tau protein neurofibrillary Tangles these are characteristic histologic findings if you actually like do an autopsy on a patient with Alzheimer's the brain shrinks there's neuronal death and there's these classic findings and that's why for Years everybody was calling this a disease of amyloid plaques we're going to treat those amyloid plaques we're going to try to uh either dissolve them or prevent them and all these treatments came out and most of them don't do very much they you know there are some that may have a little bit of benefit but we're not really winning the we're not winning the war and so so that made people look for the next level you know what maybe it's not the amyloid plaques maybe it's something that occurs before that and I just want to point out that Dale's cognoscopy testing is looking for those things that are occurring early and there's really three basic areas which we just talked about one is metabolic do they have insulin resistance is are they overweight are they eating the foods that we know are not healthy for you like high glycemic carbs a lot of carbs a lot of sugar a lot of salt that's also associated with so one is metabolic and then the SEC and insulin resistance and high glucose is a major part of because in the brain of patients with Alzheimer's one of the earliest changes is insulin resistance of the brain how do you test for that well I I know how to do it in a in a mouse is it destructive though like yeah so what happens is the brain um the regions of the brain that uh require that use insulin to help take up glucose okay so insulin is a hormone that helps cells take up glucoses of fuel and the classic insulin sensitive tissue is the scallop muscle and the Scala muscle uses insulin to help bring take glucose into the muscle to give it fuel in the brain the we we used to think the brain was largely uh insulin insensitive uh you know glucose can go into the brain freely without insulin well it turns out that's not true there are regions in the brain that like that re that use insulin to help bring in the glucose and those areas become resistant to insulin in early Alzheimer's and so you can do things like pet scanning and things like that to look for glucose uh utilization and if there's an impairment in glucose utilization in other words the brain's not metabolizing the glucose well you can actually measure it and um and so so metabolic is one of these three characteristics that you're looking at and the other two just real quickly is the second one is inflammation and systemic inflammation is now known to be a major risk factor for heart disease Paul ritger brilliant scientists at Harvard has done all these work where he measures C-reactive protein this is the same test you're doing the hscrp if it's more than three normal is like less than one if it's over three it means that you have inflammation you have systemic inflammation you may not have a fever your why count may be normal you may feel fine but there's low grade inflammation in your body and that's also seen frequently in people with metabolic syndrome so the CRP is like the perfect test uh Paul Ricker believes that everyone should have that test done if you have an elevation in CRP it increases your risk for heart disease it increases your risk for um for hypertension it increases your risk for kidney disease and I believe it's inflammation is well we know that inflammation in the brain is one of those early findings of Alzheimer's and I'm I don't know for sure but I think C-reactive protein has it been looked at for as a risk factor for Alzheimer's yeah yeah and it is so yeah anything with increasing inflammation yeah so so that in the cognoscopy score that Dale's using he's looking for inflammation which because we know inflammation in the brain is an early finding he's looking for metabolic changes like insulin resistance because we know insulin resistance in the brain is is occurring and the other one is energy status energy there's there's really two kinds of energy there's the energy that we we actively make and we're using it so that I can talk to you and you can talk to me and we can if I need to escape I'll run out that's how that doesn't become necessary myself but but that that energy is ATP that is the currency that is what uh our bodies make and uses as uh the way we we use energy we use ATP and that's the active energy but there's also stored energy and stored energy is fat you know and um and so when you eat food which is a calorie Source we make energy and some of it is ATP and some of it is fat fat and you know typically we try to refill our ATP and then the extra goes to fat and and this is how normally it works and so uh we usually have good ATP levels but what has been discovered in Alzheimer's is that ATP levels the energy and the neurons in neurons is is low early on you can show it drop in ATP and it gets worse as Alzheimer's progresses so our brains don't you know the neurons do not they're not taking glucose up as well which is the fuel and they're not making as much ATP so the brain goes into a low energy state exactly and Tom you mentioned earlier you know how do you check in a human if you've got insulin resistance in the brain as Rick was saying and some very nice work from Professor Ed getzel out of UC San Francisco showing that if you look at neural exosomes you can literally look at tiny fragments of cells these are about 100 nanometers little fragments of cells that break off from cells throughout your body in the brain these actually traffic through the blood you can isolate them and you can actually measure the insulin resistance he's published this 50 years ago blood test you can do it in a blood test now the this has been a research tool it is it's coming online but it's not yet commercially available but you can so I can't go to my doctor yet you can't go to your doctor yet and ask for that but it's coming pet scans yeah and so one way to do that exactly and it goes exactly with what Rick was saying what is the signature for Alzheimer's when we as neurologists look at a brain you see temporal and parietal reduced glucose utilization and so you know it fits perfectly with this notion that you are dealing with an insulin resistant State and the brain is simply not using this but it's also interestingly not using the only other fuel it can use which is ketones so you have a real Energy emergency State when you have cognitive decline you're not able to use the glucose because of the insulin resistance you you actually can look at differences in signaling but you're also not able to produce and utilize ketones because one of the things that prevents you from making ketones is a high insulin level so it's going to worst in both worlds yeah okay so uh let's recap where we are because I think that this is really important and I think this is going to take us into now needing to talk about the switch and what's actually going on here okay so as somebody who for a very long time I had I was hyper inflamed I probably I didn't understand that I always thought it was kind of funny but you could take your fingernail and write your name in my skin and my skin would just welt up and my dad had the same thing and I obviously didn't realize hey this means you're gonna die young uh was not that sharp unfortunately and as I got older though and I didn't put two and two together I started having chronic wrist pain and I had burn marks on the back of my hands for years because I was icing them so often that it was like leaving this little burn mark and I then met Peter attia and Don degasino and they said oh dude you've got to be eating fat like this is crazy because I was doing what I'd Now call rabbit starvation basically the vast majority of my calories were coming from protein I was in taking as little fat as humanly possible because fat makes you fat right so I was convinced uh and I already I'd gone low carb years before that so I thought well I'm low carb my diet is clean like I couldn't like I assumed my wrists were like a genetic problem and when they said hey you need to try going to being able to be metabolically flexible and produce ketones uh so try a high fat diet and stay low carb but actually go moderate protein as well let's see now I hated it because I got keto flu I did not do it well but my wrist pain went away in like three days did you measure your uric acid I didn't I don't think I'd heard of uric acid at that point unfortunately yeah because a very high protein diet can raise uric acid now normally we don't think of the uric acid as being that much of a problem but um in when you're on a keto diet or when you're on a low carb diet but it can when it gets high enough it can cause inflammation like big time and it can cause gout yeah and uh but it can represent like with wrist pain knee pain ankle pain before without having a complete uh inflamed attack because when you're on a keto diet or low carb diet you're there's a the ketones actually suppress inflammation to some extent so you can have kind of like a pseudo you know you have gout but I mean you have a high uric acid and you may have problems with it but you may not actually manifest full gout because the ketones are anti-inflammatory okay so let me press on that so are you saying that by being on a ketogenic diet which I will Define as a diet that elicits a 0.5 millimol or or higher Ketone distribution in the bloodstream so you're on a diet that produces that I could still be high in uric acid yeah so ketones actually so there's this really interesting aspect so uric acid is generated from sugar you know eating fructose which is like in table sugar and it's also in high fructose corn syrup so you can get a high uric acid from eating carbs you know that contain fructose but you can also make uric acid from protein and um and it's not as much of a problem if you're on a low carb diet because one of the things your acid does is it acts to convert glucose to fructose it's like a it it can generate fructose in your body but if I didn't realize until research you're on a low carb diet you don't have that much glucose around to convert to fructose so the uric acid you know isn't quite as dangerous in a person on a low carb diet it can often go up though to eight or nine or even higher but there are many cases of people on low carb diet who will develop gout interestingly the you know it's not usually as a serious an attack of gout as you know and when a person's on a normal diet with carbs and stuff and that's because the ketones are anti-inflammatory if you had to Ballpark me how many um grams of protein so I'm about 185 pounds how many grams of protein would I have to eat to be in that state because my gut instinct and you gentlemen are going to strike me dead if I'm wrong here but my gut instinct is you could never eat enough protein to be considered high protein and stay ketogenic like you'll get kicked out if I eat too much protein I'm boom I'm out of ketosis yeah because the protein some of it gets converted to glucose yeah so am I crazy or is is my vision of high protein like so ultra high as to be nonsensical so so it turns out that the when you're on a ketogenic diet the uric acid goes up for two reasons one is the high protein but the other is the ketones actually block the excretion of uric acid so they it goes up from both unfortunately so it's very very common for people on a keto diet to have um you know a uric acid of seven or eight or nine whoa but then over uh several months it will tend to come down it will tend to come down do you consider a ketogenic diet how healthy or unhealthy I think that in general they're fantastic diets even though uric acid can get that yeah so this has been the Paradox because uric acid does go up and so for people that don't know about uric acid give them a quick primer because I'm reacting like it's the devil's Brew so give people a quick primer I think of uric acid as bad part because of your work so uh give people a primer on what uric acid does yes so uric acid is a substance that's in everybody's blood we all make uric acid from when we break down energy or uh when we break down DNA or RNA it's basically nucleic acids when they get broken down they make uric acid and then we have to excrete it humans have to excrete the uric acid through the kidney or the gut other animals actually can degrade uric acid because they have an enzyme but we lost that enzyme 15 million years ago and we had a mutation and I think it's actually plays a role in some of the problems we have today but but anyway that as a result uric acid tends to be higher in humans because we don't degrade it and we have to excrete it through the gutter or the kidneys so like a uric acid and a mouse or you know maybe a level of one and the normal level in a human is around five so we have a much higher level and when you go on Western diet it actually goes from about three on a hundred gatherer diet to about five on a western diet and then when it gets to seven which is when you start eating a lot of sugar shrimp and beer you know this sounds good to something wrong shrimp and beer it's quite the uh but anyway when you start eating a lot of foods that can make uric acid then what happens is you're because we don't degrade it it can get up to seven or higher and when it once it gets up to over seven it can cause the disease gout and gout is this really painful disease it affects maybe nine million people in the U.S and it's an arthritis and it it usually causes red hot tender joints and systemic inflammation the C-reactive protein goes up um you know you can have a low-grade fever during attack and even after the attack most people with high uric acid show evidence of systemic inflammation there C-reactive proteins frequently High it stays High and the reason is because these are tax are from crystals of uric acid that the deposit in the joints and they don't really go away so the attack goes away but the crystals are still there and they cause this low-grade inflammation Reese recently we discovered that they can also deposit in the blood vessels and there's now there was a paper in Jama showing that like 70 percent of people with gout have some urate crystals in their aorta or their coronaries and it correlates with increased risk for heart disease so Paul ritger has been saying you know inflammation is a major cause of heart disease and the truth is that high uric acid can cause inflammation and a p even when you're even when you don't have an attack of gout and so uh and and but but what's interesting is if you go on a keto diet you uh so a lot of fruit a lot of uric acid comes from the sugar from fructose and uric acid actually amplifies is made when you metabolize fructose you make uric acid but then uric acid helps convert glucose to fructose in the body so it's like a cycle a vicious cycle so when you go on a low carb diet you break that cycle to some extent because you're not eating so much carbs but you the problem is ketones block the excretion of uric acid so your uric acid can still go up so a real problem is that you know high uric acid you know is associated with heart disease It's associated with obesity and diabetes uh and but the the complicating factor is that um keto diets which generally helps block obesity and diabetes can still raise uric acid so the question is can you say that ketones block the secretion of uric acid so how how is it going up if ketones are blocking it uh so ketones black the excretion of uric acid and the tubules of the kidney so you can't get rid of the uric acid so it goes up in the blood oh oh I see what you're saying it stops us from getting it out yes exactly from getting it out and so and and it usually only lasts you know for the first few months but there are some people who continue to have a high uric acid and and when you say that you had evidence of inflammation high uric acid causes inflammation it causes pain in the wrist so I was just thinking that maybe you were one of those people who had a uric acid of nine on that diet and the the issue is though is remember the key the ketogenic diet is what caused my inflammation to go away right so so I had it during my rabbit starvation okay so ketones are anti-inflammatory so uh several people that I've collaborated with are looking at you know for example Ben bickman maybe you've interviewed him yeah so Ben's uh doing some studies to show that when the uric acid goes up on a keto diet that it's fairly innocent because uh the ketones are anti-inflammatory and can block the pro-inflammatory effects of uric acid so uric acid is mainly this thing that causes inflammation and um and you know ketones block inflammation so it's it's sort of like the way to stop it so your uric acid can go up if you're on a keto diet you may not suffer from the inflammatory effects of uric acid uh so so that's what we're thinking but there are many cases of people who still get attacks of gout on a on a low carb diet I actually I don't know so much about a keto diet but so that you know it's a balance of a good guy the ketones and a bad guy the uric acid and so which one dominates could could be important but in general a low carb diet and a keto diet are are diets I recommend in general aggressively critical distinction here so many people get this wrong a keto diet versus a plant-rich keto diet it makes all the difference so for brain health you want a plant-rich ketogenic diet with appropriate periods of fasting so you want to get the ketones up you want to have the low carb diet but you don't want to have just a pure meat diet why is that so I'm ultra high I get most of my calories from meat so if you're gonna so change my life right now I want to hear about it so what what is the difference how how does it work mechanistically let's change your future for the better absolutely so first of all as you probably know there are now increasing reports coming back from people because of this carnivorous approach with ketones who are end up ending up with vascular disease and ending up with heart attacks and strokes so controversial or like when you go and talk to somebody who's hardcore uh carnivore uh obviously they paint a very Rosy picture I will say anecdotally and yes I understand the limitations of anecdotes but anecdotally every time I've tried to go primarily plant-based I don't feel good so now I've never looked at oh maybe I'm just doing it wrong maybe I just need to supplement but I'm always skeptical of anything where I have to supplement to get where I need to be yeah so what is happening when I intake meat what's happening or if it's no meat isn't an additive problem it's you're missing something what am I missing or vice I think it's a good point the the pure carnivore diet where that really works well is for people who have a tremendous amount of inflammation and whether it's related to the lectins that Steve gundry likes to talk about or whether it's related to something else that you're responding to you know that's person of you know that's personal uh it may be different for each person but if you look for example at apoe4.info this is 3 500 people who are apoe4 positive this is a common risk factor for Alzheimer's disease about 75 millionflammatory do we know yes because well for other reasons as well it doesn't allow you to get rid of amyloid as well but yes the the predominant issue there is it is and of course as Rick will tell you it also has to do with fructose but it is a pro-inflammatory gene it is at the primordial apoe and it's interesting because it was different in our uh in our ancestors so that the simeons as we became the the hominids between five and seven million years ago the initial was we were all apoe4 homozygous for 96 percent of hominid Evolution we've all been apoe44 which today confers about a 70 lifetime risk for Alzheimer's it's the major it's the dominant way we've got 75 million who have a single copy in this country we've got about 2 million uh sorry about about almost 7 million two percent of the population in other words that has uh two copies and they're at very high risk for Alzheimer's disease and so the the the point here is that they have to be careful about a carnivorous diet because they tend to jump up their their LDL particle numbers they tend to jump up their triglyceride to HDL ratios and they're at high risk for heart attacks and strokes now again if you're going after inflammation and you don't have issues with your vascular status then it's probably fine to have a carnivorous diet but for most people and certainly for Alzheimer's disease the phytonutrients just take one of many polyphenols alone High polyphenol associated with lower Alzheimer's disease take the risk you know we've all heard so much about lecanumab which was supposed to be this miracle drug it's it's the only really the only one of the anti-amyloid antibodies that seem to have an effect what it doesn't make you better it doesn't keep you the same it slows your decline in Alzheimer's in the early stages by 27 percent now what does better than that bill multi-billion dollar drug extra virgin olive oil alone did better than lecanumab can I add that to a high meat diet and get the same effect you can certainly add it to a high meat diet but you have to remember that you're missing the polyphenols you're missing the phytonutrients you're missing the high fiber now what do you do for fiber well so I do eat vegetables it's just that I would say 65 to 70 of my calories come from uh eggs and animal protein I guess that is animal protein uh meat and then the remaining 30 to 35 is vegetable matter okay so at least you're you're staying away from the high carb which is great I don't touch carbs my diet is very what I call clean I'm always looking to improve but so I eat a lot of eggs I eat a lot of red meat I eat a lot of um pork I eat a lot of fish um beef I never say that so those are the like my Mainstays and then I cycle through maybe 10 different vegetables okay um and lots of extra what are your Ketone levels Lots uh I'm not on a ketogenic diet now so I can feel though when I click in probably I could tell you if I hit .7 I might miss a 0.5 but I'm so because I intermittent fast a lot yeah uh and I tracked religiously my intermittent fasting over an 18 month period and it came out to be about 17 and a half hours and that includes weekends holidays everything just over the the whole time about 17 and a half hours so I mean some days I'm going 19 20 hours right uh so at that point I'm going to kick over to ketosis uh so I'd be at a 0.5.75 somewhere in there and I can feel that so I would say right now I can tell you I'm not in ketosis uh just because it's a weekday so I probably only did 16 17 hours Great point and okay and do you know your apoe status I don't so this is in fact I want to ask you more about this so if for however much of our evolutionary past we were double apoe4 yeah and 96 as well so what has changed now is it diet is it some other genetic mutation that makes apoe for or is it that we live longer that makes that such a problem why aren't monkeys having an issue with this so interesting monkeys have a different apoe and they're so there were multiple mutations between the chimp for example between between our common ancestor and the first hominids and so we picked up a specific mutation which is an Arginine actually instead of a threonine and you have a what uh what Professor Robert Maley who discovered apoe has termed uh a a domain interaction so if you have apoe4 your apoe looks like columns on a house basically it's held together because you have a positive charge interacting with a negative charge however then just about 220 000 years ago so relatively recently in terms of overall Evolution apoe 3 appeared and then just 80 000 years ago apoe 2 appeared and these are less pro-inflammatory so guess what you're not as good at fighting off you know you eat raw meat that's got microbes in it you're not going to be as good at fighting off the infections with an apoe3 exactly and also you don't do as well with starvation again comes back to Rick's work with with fructose and with this approach that you're taking in periods of starvation but it gives them less inflammation so that they tend to live a few years longer and they have a much lower likelihood of Alzheimer's disease and what's changed is the way we live what's changed is what works exposed to in our homes with with mold and mycotoxins the sugar that we're eating just that the just you know Rick's research these are the things that have changed we are we are not uh we don't have the same sort of uh intake of plants we we do have a lot more carnivory so all these things have have changed and that's why you know you may be in perfect shape and you can certainly check that out with a cognoscopy see where you stand with your metabolism with your vascular status and I don't know if you've looked at your carotids or you've looked at here but it's been seven or eight years yeah so so you know if your vessels are looking good um and and you've probably seen these pre-nuvo scans you can look now your whole body to see if you have any early tumors you can look to see whether you have uh early changes with your microvascular status in your brain these are good things to know um okay so uh we have inflammation obviously playing a huge role your diet is really uh particular what I want to start getting into now let's bring it all together with the switch why this matters how it ties to uh Alzheimer's so what is the switch yes so the switch refers to a biologic change in which uh an animal suddenly starts to gain weight uh become insulin resistant and develop features of metabolic syndrome it's it's an actual biologic change so normally animals try to maintain their weight at a you know regular weight if you feed them extra food if you put a tube down their mouth and force feed them and then you take the tube off they'll go right back to their normal weight if you fast them for two months and then you stop fasting them they'll go right back to the weight they should be at that time of the year I mean it's amazing animals regulate their weight beautifully and we probably did two but we're not doing it now and the when we were trying to figure out you know what this what what triggers this change and you know it's most noticeable and like animals that are preparing for uh hibernation or for a long distance migration you know the bear will maintain its weight during the summer uh you know can eat more one day you'll eat less the next day you know it just maintains itself and then about eight weeks before it hibernates suddenly it changes its Behavior it gets hungry all the time thirsty it starts foraging for food it becomes insulin resistant it starts eating a lot more than it normally does it can gain 10 pounds a day whoa yeah it they have a contest to take a picture of the fattest bear on the internet and in the fall because they get really really fat these hibernating bears before they hibernate they they want to put on that fat and then when they hibernate they will not eat you know they'll go to sleep and they'll not eat for like six months they won't drink water and they use that fat to produce energy that they they live off their fat so fat is a good thing in nature you know my book nature wants us to be fat you know talks about this but but the fat they when they break down the fat it isn't just the energy that's produced uh the ATP but the the fat also produces water so when you break down fat you're producing water so so uh this switch is this switch going from a point where you're regulating your weight till suddenly you're gaining weight and it was all meant to be a survival mechanism to help the animal uh in preparation for a time when there may not be food around and so the question is you know what triggers that switch and it turned out you know from our work we we're convinced that the major trigger is fructose and fructose is a sugar uh it's in fruit and honey which we think of as healthy but it's also in table sugar it's in high fructose corn syrup and table sugar half of the table sugar is fructose and half is glucose and we eat a ton of sugar and we eat a ton of high fructose corn syrup so we get a lot of our fructose from added sugars maybe 15 of the average American diet is sugars but these uh the the we also can make fructose as I mentioned earlier and we can make it in every organ including the brain and the thesis for what causes Alzheimer's is that it's fructose production in the brain that's causing Alzheimer's and you make fructose from glucose that's the only way you can only make fructose from glucose so when you're in a high carb diet you're making fructose all the time and especially high glycemic carbs because uh when the blood glucose goes up that really converts that triggers the conversion to fructose you got more substrate you know to convert the glucose to fructosis there's more glucose there's going to be more fructose meat and the and salt turns out to activate that conversion as well so it turns out that salt can increase fructose production and red meats have been Associated these Umami foods they can help convert the glucose to fructose and so red meats salt why red meat because they contain purines that raise the uric acid and the uric acid can help convert glucose to fructose so you got you got you got two major mechanisms you so the when you make fructose you make it from glucose so high carb diets are you know a big way to get it but then salt and red meat uh can trigger the conversion of glucose to fructose now I'm going to answer uh you know your question is red meats okay for you uh and you're not you're not on a high carb diet so you know red meats are associated with Alzheimer's red there are a couple papers that show increase red meat intake is associated with Alzheimer's that's scary for people who are on a carnivore diet but it may not be true for people on a carnivore diet because we according to our work it's the fructose that causes the problem in the brain it's not the red meat and the red meat makes uric acid which may not work very well to convert glucose to fructose in a low carb diet because you don't have a lot of glucose around now if you're eating a lot of protein where you where you're making enough glucose maybe that becomes a problem but but in general um you know this might answer your question this issue of you know is red meat bad plant products are probably probably better in general for you know on the regular diet but if you're on a carnivore diet you're not eating a lot of carbs you may not have that it's conceivable you may not have that problem probably don't very interesting and if I remember right salt is the same way yeah so if you're eating a lot of salt right and you have glucose in your system then that's going to be converted but if you have salt but no glucose then the odds are it won't yes absolutely that's why salted french fries and salted pretzels and salted potato chips are so bad because the carbs the potato chips gives you the glucose the pretzels give you the glucose but the salt helps convert that glucose to fructose and it will do it in the brain we have given high salt diets to animals and we can show an increase in fructose production in the brain so and um and there's a a Dr Sherwin at Yale who gave glucose and just infused glucose in people and if he brings the blood glucose up we know it gets converted to fructose and he showed in people that it that a brain fructose levels go up you can just see it like after about 40 minutes an hour the fructose levels start going up in the brain that is scary because uh our work suggests that that is could drive Alzheimer's it's not been known for a long time that diabetes increases the risk for Alzheimer's but you know if you do if you can control your diabetes Well and keep that blood sugar low you're going to reduce your risk significantly it's I don't think it's diabetes that causes uh you know Alzheimer's uh but it the high glucose converts to fructose and I'm just going to say one thing here when you talk about Alzheimer's that's critical you're also talking about mental performance so the things that we do to prevent you from getting Alzheimer's make you sharper there's no so it's not you're not just talking to people worried about Alzheimer's and then the other the third piece of this is that you're also talking about people who've had covid-19 where you know that so many people get get brain fog and it turns out unfortunately that many of the mechanisms are in parallel and it's already been shown that people who developed covid-19 are at increased risk for developing Alzheimer's whoa so the things that you're talking about today are for people worried about Alzheimer's or for people who want to think better on a day-to-day basis and for people who've had covid and want to make sure that their brain fog doesn't ultimately slip into degeneration so this is a widely applicable situation you're talking about here okay that's super terrifying yeah and I think that you've found in your studies that insulin resistance is a major risk factor for Alzheimer's and counts for maybe half of the patients are very common of course metabolic syndrome there are about 80 million Americans or so who have metabolic syndrome it's incredibly common and that includes insulin resistance so it's just what you're saying the way we live the things we're exposed to the foods the ultra processed foods that we're eating these are these are all what are colluding to give us such a common way to die through Alzheimer's about 15 percent of the population dies from Alzheimer's and as I said no idea it was that high yeah so the fact of the matter is it's it should be optional and for your generation you know the the most the vast majority of people should be able to avoid this problem through the very things that you're talking about today um so that brings us to fructose uh we know we're eating a ton of it we know we're converting a ton of it given the things that you just taught us um Thai fructose for me to the bear it certainly was between the lines and what you said but I'd love for you to make it explicit the the idea of a yearly cycle for anybody that's ever heard like I eat fruit but only in season I was always like what the what does that mean yeah so walk us through that so so you know we we think of fruits as healthy and in many respects they are healthy and I recommend fruits but if you eat a ton of fruit and I mean a ton you can get a lot of fructose that way so fructose is the sugar in fruit and bears in the fall will start eating thousands of berries and they'll they they love honey too and they search it out but they it's mainly berries that they eat they can eat 10 000 berries in a 24-hour period people have counted the seeds in the scat and um anyway when you eat that much fructose you can activate the switch and it's not the fructose that makes you fat it's that fructose makes you hungry and fructose then you then and it causes a thing called leptin resistance where you can't control your appetite and so so I know there's a but in the paper you guys break them all out so you've got hunger you've got leptin resistance yep foraging stimulates foraging uh so fructose does is that different than hunger yeah so hunger is you you're searching I mean hungry as you you want to eat but foraging is the process of going out and searching for the food we'll talk about foraging in a bit because it's it's the key it's the key uh uh Insight that led to this hypothesis hmm and see that coming okay so hunger leptin resistance foraging uh it's also decreasing your ATP production yeah so what what happens so to break down the switch the first thing is it stimulates hunger and thirst both and it stimulates foraging where you have to go out and and search for food it also stimulates uh food intake and actually it uh it it's it's blocks satiety this feeling that of fullness so that you keep eating that's the leptin resistance yes so you eat more than you should it blocks the break in within the cell it has this unbelievable trick that it does and the trick it does is that it lowers the ATP you're eating calories you think your ATP levels should go up but remember energy is both stored energy and active energy and what it does is it stuns the mitochondria the mitochondria the energy factories that make ATP so they turn the mitochondria down and ATP production by the mitochondria goes down so where does the energy go it has to go to the stored energy which is fat and it blocks the breaking down effect to replace the ATP so the ATP levels stay low for quite a while like if you drink a soft drink I can do an NMR of your liver and your ATP levels are going to fall and they're going to stay low for for a while until they eventually recover and during that time you'll you know it stimulates hunger foraging and and it's blocking the the oxidation of the the breaking down of the fat so the fat accumulates calories are going into the fat but you're not breaking it down so the fat stores go up ATP levels stay low the 18 low ATP levels are like this alarm signal hey I don't have enough energy I'm a in a low energy state I'm going to eat more because my my bodies tell me that I'm in a low energy state and so uh your blood pressure goes up to help maintain circulation pressures go up in the kidney to help facilitate excretion because it thinks that you're under attack I'm under attack and that's what fructose does it's the only nutrient the only nutrient that lowers ATP in a cell all the other nutrients do increase the ATP but glucose is still a culprit you're right because what happens is when you eat fructose very little gets to the brain but fructose stimulate fructose and glucose either of them stimulate fructose production in the brain so although if I label a fructose molecule in this sugar and I eat it most of it gets removed by the liver and the gut and the circulation very little of it gets to the brain this was you know the Trap how yet fructose production goes up in the brain when you eat sugar and it's from both the glucose and the fructose and the glucose is the more important one I think actually I don't know which ones they're probably both equally important but you're right when the glucose levels go up and when you're insulin resistant you are making fructose in the brain talk to me about the insulin resistance in the paper this plays a pretty fascinating role in terms of what's going on why why would insulin resistance ever be evolutionarily advantageous yeah so so it's pretty complicated but uh I'm gonna break it down to two things so first off there's the insulin resistance in the muscle so there's and then I'm gonna talk about insulin resistance in the brain okay so uh so when you eat fructose you wanna it's it's it sets off an alarm signal that says hey I'm under attack and so uh and and I need to get food but I need to conserve my energy so the way the body does that is it it stimulates foraging which requires energy right so you have to go out and find the food that's going to cost energy so it drops the resting energy the resting energy metabolism when you're not doing anything drops and so animals will kind of huddle they'll kind of like become couch potatoes you know because when you're not at when you're not doing anything you kind of go to a lower energy State and this helps conserve energy so it's all about the the animal thinks it's running out of energy so you you when you're not exercising or you're not foraging your energy goes down and when when you are forging you can maintain the energy you need okay and and and insulin resistance has a role in dropping that resting energy because your skeletal muscle uses a lot of energy and when you become insulin resistant the muscles not taking up as much glucose because uh it requires insulin to take up the glucose so you become insulin resistant you lose the muscles kind of going into a low mode State low energy mode and unless you're like foraging and then it will use it what it's got um and then also the glucose levels will go up in the blood because there's less going into the muscle and there's certain regions of the brain that don't require insulin and they can use that glucose to help think and thinking is critical if you're going to survive you know if if you go into energy uh you know drop your energy needs you still want to be able to think it through so that's how the systemic works now in the brain it's an amazing mechanism and that is that fructose does also causes insulin resistance in the brain and if you give fructose to an animal they get remember the three things that we talked about with Alzheimer's the earliest one is inflammation fructose if you give fructose to an animal they get inflammation in the brain in the same sites the hippocampus which is the memory centers the second thing is if you give fructose to an animal they get insulin resistance in their brain that you can prove and they and they also get mitochondrial remember how fructose blocks the mitochondria and suppresses the ATP you see that when you get fructose and it's in the same sites where Alzheimer's occurs so the three characteristic of Alzheimer's which is low energy low ATP mitochondrial suppression insulin resistance and inflammation these are all what fructose does not just systemically but when you get fructose to an animal it happens in the brain and if you raise glucose fructose goes up in the brain and you see that you can reboot your life your health even your career anything you want all you need is discipline I can teach you the tactics that I learned while growing a billion dollar business that will allow you to see your goals through whether you want better health stronger relationships a more successful career any of that is possible with the mindset and business programs in Impact Theory University join the thousands of students who have already accomplished amazing things tap now for a free trial and get started today so so that's really interesting so what why would we want the brain to become insulin resistant and this was the Twist and thank you uh Dale and thank David perlmodern our discussions with uh uh other neurologists as well to try to understand this but it it turns out that foraging is a specific behavior that requires activating some regions of the brain and inhibiting others it's uh it isn't like hey I'm just going to go out and you know find a deer you know it isn't quite like that so to forage you you actually uh have to develop exploratory Behavior it's it requires you to go into areas you may never have been so you had there's an exploratory component you have to be able to move fast so that your locomotor activity you you have to just keep going you can't take too many breaks because you got to find that food you have to have good visual cues so that if you're looking around and you see a piece of food you know something that you can eat you you catch it you and the visual cues have to light up you know some people if there's a piece of cake in the room you find it immediately you know then I have that activated at all times yeah I know where those chocolate cookies are you know um anyway so the visual cues had to and then there's certain regions like you have to decrease your self-control you don't want a lot of self-control a lot of our cortex is involved the frontal cortexes you know says it tells you you know um I don't want to go into that cave because there's there could be a line in there but you don't want to have that much self-control because if you're trying to find food for your life you've got to be brave enough to go in there so bravery impulsivity uh you know short attention you have to scan things around you can't deliberate if you deliberate and focus on one thing for a long time you're going to miss everything so it turns out that there's regions of the brain that are important for attention deliberation self-control impulsivity and and certain regions of the brain there's this one region of the brain that you stimulate it and animals forage and that uh if you give fructose to an animal or fructose you know you you know this this is involved in forage and if you um if you give fructose to a human they've actually shown that the frontal the blood flow to the frontal cortex goes down blood flow to the temporal and cortex goes down blood flow to the hippocampus goes down it's trying to reduce the activity there and um and also it's associated with you know uh impaired glucose utilization in these areas in insulin resistance in these areas so the fructose is working to create insulin so there's less fuel going in there's less fuel utilization it saves energy 20 percent of our energy is from the brain so this is another way to conserve energy but at the same time it's it's reducing our self-control uh allowing us to be more impulsive and uh allowing us to forage so great state to be in if temporarily you need to go be in beast mode get as fat as you can because you're about to hibernate but really atrocious if we leave that switch on all the time which is what we're doing now so Dale walk me through so we we have this evolutionary Advantage which allows us to survive this seasonal cycle where we know there are going to be times of Plenty and there are going to be times of lack and so we have to be able to survive the times of lack so by break taking our metabolic efficiency by leaving some of the glucose in the bloodstream so it can be used to store fat by triggering the desire to go forage and all that all good in a sort of micro moment why do they lead to alzheimer's when the switch is left on yeah great point and you know I just come back to what Rick was pointing out a minute ago that foraging you've got you know one of the most common things that happens with Alzheimer's patients is they wander that's why they put signs on the back of these patients and what do they do they wander off and you say what are you doing oh I'm trying to go home or I'm trying to do this or I'm trying to do that well this is foraging Behavior Jesus so so what happens is that very this is very much analogous to the issue of stress that is then resolved versus chronic stress we all know that you get a little stress it is hormetic you actually get this hormetic response where you do better with ongoing stress and then it's resolved then you have some stress and you're now you know you're making more stem cells you're responding a little bit about it you do this exactly now you do this and you just keep it chronic which is the big problem chronic stress now you've got hypertension now you've got Neurosis now you've got all these things and I think Rick has made a really good point of this that this is ultimately what Alzheimer's is your body has responded to insults and we've been interested for years in all the different insults you've got to look at what's driving that innate immune system and where that actually is that's got a memory that's in your endothelial cells of your blood vessels it's in your tissue macrophages so that's the microglia in your brain and it's also in your bone marrow so you're now hyper responding to things like covid-19 and you can drive that up by things like by by eating saturated fats by not having enough polyunsaturates by salt all these things so what we see as Alzheimer's and this is why it's so relevant for the way how sharp you are on a day-to-day basis this is the end result of these ex of these responses to stress so we are stressing ourselves out repeatedly over the years with our exposures with our eating of fructose basically we are driving a system Beyond its evolutionary design you know we again we were not made to eat a lot of sugar and we're doing it it's just like you know jumping out of it of a window from the second or third story you might survive a few times but you do that you know 10 times a day for 50 years you're going to have some major major rheumatologic and orthopedic problems so we are triggering this thing and unfortunately that we're actually making each time you activate your innate immune system which you can do with fructose each time you're turning down your mitochondria just as Rick was explaining your body makes a little amyloid what is it there for it is there to respond to insults it it's really interesting stuff It Coats the bacteria it actually is antibacterial anti-parasitic antiviral it's an amazing molecule it's actually there to protect you but part of that and this is what I was asking Rick about last night because to me this is the billion dollar question why is it that your body has brought together the thing that is your innate immune system that is responding to these insults trying to help you but it's put that together with reducing your energy and literally downsizing your network and that is the surprise here that your body hasn't evolved a way to say I can get rid of the P gingivalis or the herpes simplex another by the way another common uh contributor to long-term activation of your innate system people who treated their outbreaks in Taiwan had an almost 80 percent lower likelihood of developing dementia just striking results a size simple acyclovir valet cyclovir things like that and that works because it's taking it's it's reducing the amount of time that the brain is under assault basically exactly so you're reducing the thing that's actually driving your innate immune system to stay on and I think do they have to treat that chronically or is that like if they have a flare-up they typically we're doing with flare-ups but yeah so some people will do it if they're having a lot of flare-ups they'll do it chronically so what's happening is you're seeing a system that has defended itself quite successfully you can see people with massive amounts of amyloid in the brain who are still quite normal cognitively it's when this stuff is now giving these the older numbers you're taking these big lakes of amyloid and you're now making the oligomers from that it's a little bit like taking troops and sticking them in a fort as long as they're in the fourth they're not out shooting and killing the populace but when you open the fort when you're now continuing to to poke the bear basically you're now going to be bringing these things out that are both downsizing and protecting and you're you're basic your body is your brain is making a choice saying I've got to fight these Invaders so I'm going to live with a smaller brain I'm going to live with fewer synapses and it's the loss of synapses that is the big problem we're losing our processing speed we're losing our ability to lay down new memory and the interesting thing is this is a program your brain is deciding look you in your life have done all these wonderful things you've got enough to live successfully for years so if you've got to give up something if I said to you tomorrow tom you can wake up and either have not able to store you're not able to store new memory or you're not able to speak calculate do your job that's an easy choice and that's the choice your brain is making woof okay so what is going on it's that makes it shrink back it's under assault I get that but why is the solution to not form new memory is it just resource allocation it doesn't have the resources or yes so you are not your supply and demand is now mismatched so you are you you know you can put your resources into fighting the pathogens or you can that's where the inflammation part comes in or you can put it into things like your mitochondria building synapses making and keeping your memory and this is why getting rid of those problems having the extra virgin olive oil keeping your inflammation low keeping your fructose low these things are all so critical for you to be at your best when you are making and keeping new synapses making and keeping new memories so talk to me really fast about the polyphenols what what are they doing are they protective against something or are they giving me a building block that I need yeah so there are several mechanisms but they are to some extent they're having an anti-inflammatory effect and they're supporting your mitochondrial function what Dale has talked about is that there are probably multiple mechanisms leading to Alzheimer's and there's infections toxins it's known that like a concussion can increase your risk and um you know genetics and you know and uh what I've been saying is that fructose may have a dominant role interestingly fructose could be playing a role in this pathway life with concussions and toxins too because the enzyme the chemical reaction to make fructose is turned on under almost on many stressful conditions it doesn't require you to be uh you know it isn't just diet so for example mild dehydration concussions cause low oxygen it causes what we call hypoxia contusion you the blood vessels aren't delivering as much blood oxygen so you get the brain kind of swells a little bit with a concussion that will stimulate local fructose production it that's why well because if you you think of fructose as trying to be a survival pathway so when it gets turned on what it does is it turns on inflammation to try to fight off deal with the toxins or whatever it tries to reduce the energy in the cell to conserve you know if you have impaired blood supply you're not getting the nutrients so to to the brain it's like a starvation state so what you want to do is you want to reduce your energy needs and if you stun the mitochondria the mitochondria use a lot of oxygen and when you when you stun the mitochondria your oxygen need goes down acutely and you you're not record you know everything goes into a low power mode so you're making less energy but you don't need you're trying to go into a low energy mode where you that you you your metabolism goes down and it it turns you you were talking about how metabolism gets turned down it isn't just the the uptake of glucose but the enzymes involved in glucose metabolism fat metabolism they all get turned down everything goes into a low power mode we're trying to protect we're under attack we're going to start inflammation we're going to reduce our energy needs and we're going to survive this attack and that happens with a concussion may happen with toxins that covid actually one of my friends measured the mitochondrial changes in Long covet it's the same signature as fructose we just don't know if the long covet stimulates fructose but it's the same signature the apoe4 is also you know the suppression people who have that they suppress their mitochondria they increase their glycolysis again it's the same Sigma signature it's like a survival pathway so whether or not that involves fructose I don't know yet but but I do know that fructose activates the survival pathway it's turned on under low blood flow oxygen low oxygen infections viral infections you know herpes simplex they may also be able to induce this Activation so it could be one it could be one main pathway and that is converged on by all these toxins and so forth and what you're doing is you're going I'm going to look for all these I'm going to look and treat the infection I'm going to look for vitamin deficiencies I'm going to look for all these things that might cause stress and um and also I'm going to look at insulin resistance and all these things and so you are making great roads incredible achievement to to slow down Alzheimer's and um and our work is a hypothesis that says that all these things may work through fructose e to eventually cause these changes I'll tell you one thing if you give sugar water to an animal a lab rat after about four weeks they have trouble walking through a mace they have trouble getting through a maze their brain starts to shrink they get the mitochondrial problems they get the insulin resistance in the brain they get the inflammation of the brain all published and if you take about 18 weeks they start getting amyloid plaques cow protein in their brains in the hippocampus probably it's you know fructose probably can be said to be a cause excessive fructose to be a cause of Alzheimer's I think we could probably say that based upon these experimental datas if you take people who have Alzheimer's and you at autopsy measure their fructose levels in the brain five to six fold higher than a normal person whoa yeah that's a significant and you come back to the switch you know just to say but there's a switch in your brain that you've talked about here but your brain is literally switching and we see this we we study this more through the amyloid precursor protein uh signaling but it's the same story your brain is literally switching from a mode of building and maintenance we can make new synapses we can learn new things we can you know we can build new Bridges basically it's now switching to a mode that is all about protection and downsizing as Rick said it's a low power mode it's saying uh oh tough times could be ahead we're now going to use our resources to fight potential pathogens to deal with toxins but we're going to live with fewer synapses so that is a switch and you can see it by the way when you study app signaling you literally go from cleavage at at one site to cleavage at three sites and then what happens this is amyloid precursor protein which is the protein that sits in the membranes that is going to give rise to the amyloid which is a tiny peptide fragment of that overall protein and this thing is a switch you can literally go back and forth between this maintenance and and building mode into a protective mode so it fits beautifully with Rick's theory of how this works through the fructose related Pathways and and the incredible thing is once you kind of understand this you can actually design uh management plan to prevent Alzheimer's which you've already done actually what you're doing is reducing fructose production in the brain through all these different measures you know reducing high glycemic carbs polyphenols some of them actually block fructose metabolism you know there's ludiolin and ostol are are polyphenols that can block fructose metabolism to some extent wow this is really coming together for me uh I'll so much so that I'm going to um I'm going to recontextualize my initial statement at the beginning of this so at the beginning of this I said uh this is all Downstream of glucose but the reality is what I'm hearing now is that glucose just happens to be the way that we put our body brain specifically in the context of Alzheimer's but it just happens to be the way that we most frequently put ourselves in the I'm under assault I need to go go into low power mode but the reality is there's a many different let's call it four or five whatever ways that we can put our brain and body in the I need to go into low power mode I need to protect I need to survive this insult so from a brain perspective it could be a concussion from a brain perspective it could be diet glucose from a brain perspective it could be a virus it could be bacteria so anything that's going to put our body into that hyper defensive mode where I'm left with the decision to survive this or to make new memories and when I have to figure out whether I can walk and talk or I make new memories I'm going to always choose the walk and talk which is why and this is terrifying people with Alzheimer's turn into basically a zombie and it's like they're not there but they're still alive there meaning the person that I knew and loved is no longer present but the reality is that they've just so chronically been in low power mode that everything is offline yeah now you hinted at this and you said it out right at the beginning it sounds like then there are things that we can do to get out of low power mode and while I can only imagine that the longer you stay in it the more damage is done that we're not going to be able to unwind that we can start unwinding some of this what does that look like what would a protocol be yeah that's a great point and you know the one of the most exciting things is seeing people who've been told that they're going to die there's nothing they can do they have Alzheimer's that they actually get better and we had people in the trial going from mocha scores of 18 or 19 which is that is out of 30 where you have significant Alzheimer's two perfect 30s doing very very well just striking improvements and and the most common thing we hear is that the spouse says you know they're so much more engaged suddenly the the synapses are firing again and they are starting to interact so what it looks like is very much what Rick was saying you're we are looking for all the different contributors because they are different from person to person but again as Rick has pointed out you could argue that the most common the most common insult that our brains are undergoing is glucose and fructose related but we do see people where it's about their uh their their oral hygiene we see people where it's about leaky gut where again as Rick has pointed out fructose plays a role we see people where it is about living in homes full of mold and the mycotoxins things like trichotheses and okra toxin a and gliotoxin these affect your immune system as well as your nervous system so there are as you said there are many ways to give yourself these insults and unfortunately the big problem with this disease and all chronic illnesses is that they go on for a long time before we recognize it so part of the medical Revolution here is for people to do more with things like wearables where we're seeing oh wait a minute you know my heart rate variability is changing you mentioned CGM earlier so continuous glucose monitoring great if you're going off scale and by the way we see the other half of that as well people who are eating high carb diets go to bed wake up at four in the morning with a glucose of 45. they've gotten significantly hypoglycemia off of a high carb diet oh absolutely because you get the Peaks and The Valleys you now get the insulin coming out and you drive yourself into these I mean into hypoglycemia which is horrible for your brain as well okay you want to identify those and address so so our protocol that we developed is about identifying the drivers and then what's causing addressing the drivers yes so we're we're addressing the inflammation so you have a standard questionnaire or is this where we get into the blood test yeah so yeah we do have a standard questionnaire and we look at uh right now we look at 150 different variables But ultimately it will be whole genome and it will be epigenome there's some great tests that are now available that haven't been available before phosphotal 181 phosphotal-217 these are literally looking at your brains pulling back because when you phosphorylate your Tau and tau is like the bolts if you're building out a piece on your studio you'd be putting out Rafters and then bolts on them to keep them stable the the tau is what stabilizes your microtubules and when your body is now pulling back what it does is it sticks a phosphorylation group on the towel which pops it off and allow allows your neurites to collapse so you're literally looking at that what's ongoing but you're now looking at it in your bloodstream you can also look at things like things like gfap which is another blood test these are all now available neurofilament light is another one and these proceed so it gives us the ability to look earlier to say ah you know Tom's brain is not doing what it should be he has to worry 10 or 15 years down the road so what do we do for these people we identify what is causing do they have inflammation so what we did we identified as you know we identified six different subtypes we say so Pete there are people where it's a predominantly inflammatory disease and you know these may all go through fructose I don't know yet I'm fascinated to find out we see people who have more of an atrophic mode so in other words they're just very low in all their supportive elements estradiol testosterone pregnenolone progesterone thyroid vitamin D all these things the bet gets to the energy component of this then there are people that have what we would call glycotoxic where they've got a high Homa IR they are very insulin resistant then we have people who have a toxic where they're exposed to either biotoxins inorganics or Organics air pollution as you know lots of interesting work on air pollution increasing risk for cognitive decline and for Alzheimer's disease and then we have people where as Rick said it's concussion related this is where you have traumatic and many people it's a combination of those things these are all insults to which you have responses so we identify those things and then if you've got pathogens we want to get rid of those and then of course we want to heal your gut we want to give you a we want to give you metabolic flexibility so you were asking before you know ketones people do better when they have Ketone levels above 1.0 millimolar BHB how often we've seen at least once per day okay and so but when we do that then what we do is the key is to make the metabolically flexible so you're in good shape because you're able to go in and out you're able to use glucose when you need it and you're able to use ketones when you need it and you're not having these high levels of glucose and you're not having the hypoglycemia because you don't have a high carb diet so those are all critical pieces to get people metabolically stable and that's when they do the best and it's interesting when people start having energetics they've got the ketones on board they're able to utilize glucose again they start to get better they start to perk up and then we have to make sure that their innate system is not being activated now one of the things as I mentioned earlier the innate immune system one of the places it stores memory is in your endothelial cells so both with covid and with Alzheimer's you're ending up with these micro thrombi and micro infarcts that over the time really take a toll on you you see this all the time with the MREs I say I store memory what do you mean is it a damaged cell or a cell that now reacts in a different way so you literally reprogramming the cell so it's not necessarily damaged you don't have to wait that long you're reprogramming it to be more thrombotic so you're reprogramming's blood clotting yes your your Repro you're basically making it so your platelets are stickier you're not rolling your blood along these nice endothelia the way you should and so you end up with a higher risk for these micro infants so one of the things we do is to treat that and to prevent people from having these microthrombi we get their innate immune systems to quiet down and relax with things like well you bring down the for the blood vessels you can use things like nattokinase and pycnogenol easy to use are these drugs these are actually supplements you can get over the counter yeah you can get these over the counter and then of course so there's one that's called nattokinase and there's one that's okinase and you can get it by eating natto I mean the other one is called pycnogenol and I again I don't you know we never recommend that people just go out and try these things willy-nilly you know talk to your uh practitioner we've trained over a 2 000 practitioners now to do this protocol from 10 different countries and all over the United States um and then for the innate system part great things like Omega-3s SPM activism is a resolving um so resolvins uh uh discovered by professor Charles searhan at Harvard a number of years ago a very interesting molecules they are Omega-3 cousins basically that help you to resolve ongoing inflammation we now want to tame that innate system and we want to bring up your energetics those are the two critical pieces and in so doing of course we also want to get rid of the pathogens that are causing this to be chronically activated Rick were you about to say something yeah I I was just going to say that a lot of uh what you're talking about this uh you know trying to improve the energy in the cell uh improve metabolic flexibility that's exactly what happens when you remove fructose you know so uh fructose you know causes metabolic inflexibility because it's blocking the fat from being broken down to the ATP it's suppressing the glucose uh metabolism through the mitochondria so if you can improve if you can re reduce fructose production or or intake you can have a theoretically have a lot of these effects including on the endothelium I mean it's just it's really uh so it's very it grounds me when you when you talk about your your approach which is to a very personalized medicine approach where you're looking at each area and then really trying to knock it down I I can see fructose is a commonality across the board and you know my um my recommendation is that everybody should try to eat healthier and um Define healthy and what I mean by that is uh because we we can show that this pathway is associated with aging too I I have knocked out this fructose pathway in animals and they stay leaned old they're smart they they uh don't develop uh kidney disease or heart disease or liver disease with age it's or it's very mild um and you know and their mitochondria stay healthier so you know I think that this is a general this fructose pathway is generally a problem that's involved in a lot of diseases aging and so forth so from my standpoint I would cut out soft drinks because of their sugar content because they have glucose and fructose they they are concentrated they have a huge amount of glucose and fructose um diet soda okay diet soda would not activate this pathway but it does make you still like sweets so you know um what about fruit juice fruit juice you should not drink fruit juice but natural fruits are totally fine because the intestine removes about three to four grams of fructose and so um you you can eat a fruit and very little fructose gets to the liver and um I would say that uh natural fruits are good because they got all your flavonols they've got vitamin C vitamin C actually counters some of the fructose effects everyone should take Vitamin C 500 milligrams twice a day it really we're going to come out with a paper showing how this thing enter how Vitamin C interferes with fructose it's really terrific we should be eating a little bit of fruit uh vitamin C I don't you know to counter fructose so um cut out reduce sugary Foods re read labels reduce high fructose corn syrup reduce processed foods they're filled with salt and sugar you know Ultra processed get rid of you know try not to eat those um try to not eat a lot of really salty foods if you're going to eat something salty drink a lot of water with it so that it doesn't activate this pathway water when you get thirsty you're activating the switch because talk to me a little bit more about water so I I am wildly ignorant on the topic but I have a gut instinct the way that people tell you to drink water does not make sense to me from an evolutionary perspective we just would not have had that much access to water so the thought of drinking like you know a liter of water every hour or whatever the prescriptions are it seems crazy to me am I off track here you're off track because because we're not living in a survival mode right now we're we're living with processed foods and high salt foods and salted chips and you know back when in the hunter-gatherers they they didn't have to drink so much water because they they weren't eating all this food with salt in it we are raising so when you eat salt what happens is the there's a salt concentration in our blood and you can measure everybody who gets a blood test when they see the physician almost everyone will get what they call the electrolytes and sodium or n a is the test for your water balance your salt water balance if you're eating a lot of salt but not drinking a lot of water then the sodium will be high and if the if you're drinking a lot of water and not so much salt then your sodium will tend to be a little low and a normal range is like from 135 to 145. and everyone said hey that's normal I don't care if the sodium is 144 I don't care if it's 137 but now people are studying it a little bit more and there was just a big paper and if you're serum sodium is on the Lower Side meaning you're drinking more water so it's like 136 to 140 you will have a much better Outlook in terms of lower risk for heart disease obesity diabetes dementia aging then if your sodium is like 144 so even though they're in the normal range the doctors won't tell you this but there's already data there the studies are out we need to drink more water and if I take an animal and I give them a high carb diet they get fat if I put them on increased water that reduces that increase in serum sodium and that is associated with less fructose production and they I can block obesity and Diabetes by just increasing water intake we polished it uh in a very good Journal and so uh it turns out that these people who are running around drinking eight bottles of water a day is probably a good thing because what they're doing is they're keeping their serum sodium down so they're reducing the conversion of glucose to fructose because remember a high salt concentration in the blood stimulates the conversion of glucose to fructose uric acid does too but salt is one of your best ways to do it so that's why salted french fries are bad so if you're going to eat french fries drink water first to bring your serum sodium down your serum salt concentration down so that you don't activate the switch when you you're eating the fries because the sodium will go up but not to the point where it will convert you know it's better to drink water in the beginning of a meal uh than in the end of a meal interesting you want to lower the sodium before you intake the next absolutely yeah yeah okay so do you have a prescription on how much water yeah it's all relates to how much salt you know if a person's not eating a lot of salt you don't need to drink a lot of water if you're eating a lot of salt or you're working out out in the sun and you're you're sweating a lot you're going to need salt and water and you just need to make sure but but here are some tricks if you look at your urine which maybe not not everyone chooses to do but really if your urine if it's dark yellow it means that you are D partly dehydrated it correlates if the urine is totally clear like water you're overdoing it you don't need to drink that much you want it to be like just slightly yellow you can also go to your doctor and get a serum sodium and you want your sodium to be like 138 to 140 maybe 142 but you don't want it higher than 142 and that means you're not drinking enough water um you know and uh I always put in this caveat when I talk about this but if you're a marathon runner you do have to watch how much water you drink because there are these people who get you can intoxicate if you drink gallons of water and on marathons when they get really dehydrated they'll keep some of them will keep drinking uh a lot of water and then the serum sodium can fall and they can they can get sick you can have seizures so you you know if you have any concerns talk to your doctor measure your serum sodium But A good rule of thumb is eight glasses of water a day uh is for the average person's really good eight to ten glasses it would be about right we want to have about two and a half liters of urine a day most people have about one and a half liter and that would be that that would be good where do hormones fall in all of this like as somebody who's rapidly approaching an age where I will very seriously consider trt um this is play a role in this is that uh one of the things where the body's gonna respond negatively where I go into low power mode or it doesn't matter there's a lot of good things about testosterone I mean it can raise your blood count it can sometimes raise blood pressure can lower your wouldn't that be bad uh you know it depends if your blood pressure goes up a lot usually it doesn't raise blood pressure very much usually it doesn't raise the blood count that much but occasionally it can usually it doesn't lower well it does lower HDL cholesterol I mean so there's some negative aspects about it but a lot of people feel better on it um I haven't really studied it in terms of what it does to fructose metabolism so I I don't know Dale are there any correlations because like my next question is going to be why do women get this at twice the rate that men get it so the hormones play a big role in Alzheimer's disease and that's well studied rapid drops for example there was a very nice study that came out of the Mayo Clinic a number of years ago where they simply looked at women who had lost their ovarian function typically they threw you know one reason or another they had lost ovarian function at the age of 40 or younger they doubled their risk for Alzheimer's even though the Alzheimer's didn't announce itself and didn't get diagnosed for many years after that if you went back clearly so that one of the hypotheses is that it's this precipitous fall and so yes men are less likely than women women make up almost two-thirds of the patients with Alzheimer's just as apoe4 positive is also about two-thirds of Alzheimer's uh and so they are about 65 as Maria Shriver has pointed out time after time this is a woman-centric disease uh and about 60 percent of caregivers as well so one of the thoughts is if you have a precipitous drop in your estradiol and progesterone you are literally taking that energetic taking those those changes away and by the way in our work in the lab you can literally trace the molecular Pathways estradiol binds to receptors estrogen receptors and that then enter the nucleus and change the transcription of genes so change the RNA made from hundreds of genes and one of the ones that it up regulates is the one that cuts the amyloid precursor protein at the good place that actually gives you the things that say Okay memory formation memory maintenance so you precipitously drop that and you're again you're pairing back on your synapses people who then go on bioidentical hormone replacement tend to do better with the highest value and testosterone and similar effect but of course when you go through andropause as opposed to menopause you tend to go down more slowly and the thought is that that may be one of the reasons by the way progesterone also a critical in detox what happens we saw amazing when I was detoxing from like metal detoxing from all anything that where you're using your glutathione and detox Pathways Organics inorganics and biotoxins when I was training in neurology back way back in the 1980s we never saw people in their 50s with Alzheimer's we would see we thought of it as a disease of older people 60s 70s 80s 90s we now know it is a disease of your 30s 40s and 50s that gets diagnosed 20 years later I thought you were saying we're seeing it in people in their 30s well so what we are seeing is one of the most common presentations we see now is a 52 year old woman and it's typically associated with menopause or perimen menopause and the current thought is you're exposed to these toxins over time and you are sequestering them in your bones in various places you're also detoxing and then you go through What's called the osteoclastic burst about a seven year period where you have dropped your hormones and you're now releasing some of these from the bone you're now undergoing bonuses exactly well you don't have osteoporosis yet but you're releasing these back into your circulation so you're now exposed to these toxins and we see presentations all the time with people and we want to of course we want to get them as early as possible help them to detox get them they'll respond very well to bioidentical hormone replacement as an overall part and then also to detox and the progesterone is an important player in the detox so walk me through sorry I just wanted to add to the the female question um so it's known that uh with menopause when estrogen levels fall that there is an increased frequency of obesity and diabetes and chronic kidney disease they all go up uh not just Alzheimer's but the risk for Alzheimer's but all in general metabolic syndrome uh and cardiovascular risk all start to increase in the woman following menopause and start being closer to males in many respects like heart disease and so forth and there are different theories for it but one one interesting one in addition to the all the wonderful mechanisms we're talking about is that estrogen keeps uric acid levels low so uh in in young women they will tend to have a uric acid lower than men and and that's why gout is really a disease of men more than women but following menopause uh uric acid levels come right up and uh become equivalent to the male and the risk for gout goes way up and if uric acid we believe is playing a role in causing this uh pathway in Alzheimer's that fructose and uric acid are working together one could argue that the increase in and the other thing which I haven't told you is that although women are protected uh the for the same level of uric acid the women show up worse effects so women have a lower uric acid before menopause but if if you take female cells and male cells and compare them with uric acid you know basically are there's there's evidence that women are more sensitive and show a greater uh consequence for the same uric acid so when their uric acid goes up following menopause they they won't just catch up they make can bypass you know in terms of these metabolic effects so one one possibility is that that that is involved in in this Alzheimer's response to besides the Direct effects of estrogen on amyloid and so forth and then while we're on uric acid we should mention the excellent book by our co-author yes and friend Dr David Perlmutter uh yeah called drop acid excellent book so yeah I had them on to talk about that it was the first time that uric acid really got put on my radar that's let's keep pushing on uric acid so what role is it is it the ambulance at the scene or is it actually driving the problem well most of these things I would I would definitely defer to Rick he is the uric acid expert but you know these things are mostly biological signaling is often in Cycles just as he was saying earlier you know it's part because it's changing mode you're literally changing you're switching from one mode to another mode so it is both it is driving it but again you where it's like it it's helpful in the beginning uh I guess that wouldn't technically be you but basically it's good in one circumstance and then it's terrible in another yeah so the way that we kind of looked at that was uh we were curious why humans have higher uric acid levels and um and so as I mentioned you know most animals have an enzyme called uricase which degrades uric acid so most mammals have a uric acid of like one or they produce it but they get rid of it yeah they produce it and they get rid of it and we lost that enzyme 15 million years ago so just uh as um you know when I was studying I have a long ass time like when I think about us compared to most animals not all animals but most animals we live longer obviously we've become the dominant apex predator so did we lose it or did we get rid of it we got rid of it like in a good way I'm saying it was a good way back then and so let me try to explain how how that works so scientists now can figure out when a mutation occurred and the mutation occurred around 12 million years ago and uh and you know so I was wondering what where were we as humans 12 million years ago and this is actually pretty human when when there were ancestral Apes that were the um they were the ancestors for not just us but for all the great apes and uh I found out that the these Apes had originated like around 20 million years ago in Africa and they were in East Africa and they were frugiverus meaning that they ate fruit they lived in the trees they lived off fruit and they were very successful and you know within a few million years there was like 20 different species of eight today there's like four or five HC or four species or whatever and then and then what happened was uh there was a change in weather and global cooling began and it was the polls increased with ice and the sea levels fell and so it's sort of opposite is what's going on today and uh Africa had was actually an island uh you know there was no connection with Europe but as the water levels fell a land bridge formed that allowed animals in Africa to migrate into Europe and uh lots of species migrated elephants rhinos ant eaters and primates these early apes and they ended up in Asia Minor and in Europe and there was it was still warm enough that there were fruit trees all year round uh in those areas and so they the Apes didn't have to change uh their their diet at all it was still the same and then global cooling continued and uh and in Europe those fruit trees started becoming less and there was a change in the forest and suddenly there wasn't a lot of fruit during the cooler season sort of like the winter but it wasn't true winter it was just a cooler period of time and the Apes started to starve and they they you can show that uh by skeletons that show that they had these striations on on their teeth that kind of look like tree rings and it's a they call it enamel hypoplasia and you get it during the growing when the teeth are growing and and it gets stunted when there's no food around and uh there's a very famous Anthropologist named Peter Andrews who uh was at the Museum of Natural History in London and he was studying these apes and I I figured you know I don't know much about archeology myself but this guy does and I'm gonna go talk to him so I flew to London met with him and he showed me all the work he did and we spent uh quite a bit of time together and uh through the I said could it be that this mutation may have occurred in the Apes in Europe he says well he says uh you let me try to explain to you what happened and he said you know our work we looked at this the skeletons and we realized that it was a European ape that became our ancestor in the European ape uh when they were starving they they didn't all become extincts some of the European Apes actually migrated back to Africa but when they migrated back they took they overcame the Apes in Africa and so that they came back because when they when they started to starve they had to come out of the trees they had to learn how to walk around not bipedal but more like knuckle walking they they had to learn how to dig up tubers and roots and eat different foods because there wasn't enough fruit around and uh and that was when the mutation occurred in the and it turned out that when they came back some went to Africa and some went to Southeast Asia to become the orangutan and they all carry that mutation showing that they came from a common animal that was we think was in in Europe so we realized that maybe that mutation may have helped them survive when the when all the Apes were becoming extinct up there and it might have allowed them to to make more fat from fructose so what we did was we took a mouse or a lab rat actually and we inhibited urocase so we made it like we mutated we didn't mutate the eurocase we just inhibited it and it's uric acid went up and then we gave it fructose and we gave another group the same amount of fructose but without inhibiting the your case and the animals where we inhibited your case become showed were much more sensitive to Sugar that's really interesting from a calorie as a calorie perspective the blood pressure went up more they've got more fatty liver even though they're eating the same amount of fructose exactly and uh weight gain is driven by calories but the rest of it is not so the blood pressure what are you calling the rest of it sorry insulin resistance blood pressure fatty liver uh all those things are independent so they would get fatty liver without putting on fat correct interesting yeah absolutely and then we we actually I worked there's a guy named Eric Usher who's uh a molecular evolutionary biologist and he actually resurrected the extinct Gene that we lost and we could put it into cells and we could show that when when a a human liver cell has your case it makes less fat from the same concentration of fructose and if you not take a human cell today that does not have the irrit case it makes a lot more fat do you inject the uricase uh we uh transfect yeah we we express the gene in the cells you can turn it back on is how are you turning it back we resurrected the gene by figuring out what the gene was and then we ex we made it and it put it into a liver cell I'm saying how are you getting it into is this a cell in a Petri dish yes I see I see so not not a human who is alive into their active liver cell but what it does suggest is this mutation was to help us survive because the mutation what it did was it raised our uric acid so that we could make more fat from fructose because fructose makes uric acid and when if you start off with a higher uric acid and you eat fructose the uric acid that's produced by the fructose goes up even higher so for the same dose of fructose the uric acid goes up much higher and you get a much bigger switch the by so our switch so it's really interesting if you take a mouse and you give it sugar you have to give it a lot of sugar to make it fat but humans are much more sensitive to sugar and this is one of the reasons well very very interesting how this all comes together so they'll go ahead you're inside I'm just going to say so my interest is okay let's imagine that this is going to be a the major player that that fructose is going to be the major player and and farm is going to go out and develop an inhibitor prevent this pathway very little that the human body does that is to give it disease it's responding to something in a hopefully positive way just as you've just explained with Evolution so my question is what's going to be the side effects what do you lose Yeah by losing this when Pharma comes up and says okay uh you know okay Professor you know we've now got something that looks really good and it's going to help Alzheimer's disease what are going to be the side effects of that of that drug well I there are actually people who lack the enzyme and they're it's pretty rare because they they don't have any symptoms so it's hard to find them but the few kindreds that have been found they don't develop type 2 diabetes they don't develop obesity so have we looked at longevity or anything yeah they they haven't looked at longevity um but the the belief is that it's pretty innocent and um in a modern context because I can tell you the the out in the wild perspective is you starve to death and die so in a moment of famine your toast whereas myself I can make seven pounds of fat out of nine calories so it's like I'm gonna survive a famine guarantee yeah so exactly that would be my prediction as if if there was like a serious famine they're they're not gonna do as well um if you block fructose metabolism then but in a modern context where you can go to the grocery store yeah not so bad yeah they might live longer the prediction would be they would live longer so I I think that so long as you know we have grocery stores filled with 20 000 different food items and and you know people are will continue to pick the foods that they want uh sometimes even when they know that they're not good you know it might be a beneficial thing to have an inhibitor hmm wow very interesting okay so just to bring this all back around if you have diabetes you need to figure out or sorry not diabetes if you have um Alzheimer's disease you want to figure out why you have it what is the insult that's leading to this whether it's a toxin whether it's your diet whatever you need to figure out what it is and then understanding that basically all of this is kicking off this switch you're turning on the fructose either you're in taking it or you're producing it but either way you've got a fructose production problem in the brain that is causing you a problem you're going into low power mode everything is shutting down retreating but you guys are the first ones to give me any hope that there's actually a way back out of low power mode and you can actually see a reversal of these symptoms which is absolutely extraordinary what is the next step in the research Where Do We Go From Here Yeah critical piece here is that when you develop Alzheimer's disease you go through four stages so you have a pre-symptomatic stage often in your 20s and 30s where you can already pick up changes on pet scan you can already pick up that signature we talked about earlier with temporal and parietal hypo metabolism for glucose then you go through a period that lasts on average 10 years which is called SCI subjective cognitive impairment where you know there's something wrong but you're still able by definition to test in the normal range and this is the problem the doctors are telling you yeah you're getting a little older it's nothing to worry about well yeah a lot of people who get older have problems but they shouldn't and that's the key if you would if everyone would just come in at those two stages either get on active prevention or earliest reversals we could make dementia a rare problem today the problem is everybody's coming in on the last two stages the third stage is called mild cognitive impairment terrible choice of terms it's like telling someone don't worry you only have mildly metastatic cancer it is a late stage of what is going to become Alzheimer's related dementia and dementia is the fourth agent by definition that means you've begun to lose your activities of daily living and even in our trial we took people with MCI and early dementia and even then for 84 percent of them improved but if you could get people early you can get it closer to a hundred percent so then I think the next step is to go after first of all to understand whether this is present in all the other things when we're seeing the other pathogens are these is this all through fructose and then I think you know this is maybe an excellent Pharma Target instead of trying to remove the amyloid which really is a naive approach and makes no sense by itself let's try to shut down the the actual drivers of the decline again I'd like to remove Upstream what's actually causing if you're living in a place that's exposing you to things you need to address that um and uh and as we've heard today from Rick you know quit eating the quit eating the fries quit getting all that salt quit you know we Now understand what are all these things that are driving this pathway that may be so common as a critical pathway for developing cognitive decline amazing where can people follow you Dave Dale uh you can look at drudison.com in the Facebook is Dr Dale bredesen uh and and same for Twitter and Instagram I mean then we have a couple of books out uh the end of Alzheimer's talking about these sorts of things but of course at the time we didn't know about about fructose until Rick's exciting work uh and then uh in a more recent one the first survivors of Alzheimer's tremendous seven stories from people who got better and they talked about what they went through amazing Rick where can people haul you yeah so uh Dr richardjohnson.com is my website um and uh I have a book nature wants this to be fat that includes the discussion about Alzheimer's and and the foods that activate this switch uh and you know I also have a Twitter account that's very similar to my website and Instagram is Dr Richard j Johnson so um I do want to say that uh to end this by saying that you know Dale's work is actually has Hands-On proof that the that this kind of personalized medicine approach Works our work is compelling but we still have to do we have to take it from the hypothesis and compelling out evidence to to actually try to prove it and so that we still have more to do but I will say that I think there's enough evidence that people need to view diet as one of the most important things diet and exercise following all these general rules that you have been doing and others have been doing of you know trying to reduce high glycemic carbs and sugar reduce salt drink more water I think that this is a there's enough evidence there that you know this should be something everyone should be doing in trying to to stay healthy and reduce their risk for Alzheimer's so I love it okay all right everybody remember that ultimately you are in control of what you do and it all has consequences and speaking of things that you should do if you haven't already be sure to subscribe and until next time my friends be legendary take care peace click here to learn exactly what you need to do to prevent Alzheimer's disease and even potentially reverse it this woman in front of me my patient her life is decimated now her life is decimated now she's in my office week after week sobbing