21st Century Medicine and the Reversal of Cognitive Decline in Alzheimer Disease (Part 2)

all right i'm dr mark hyman and this is dr dale bredesen i'm the director of the cleveland clinic center for medicine and dale is the founding president and the ceo of the buck institute uh for research on aging looking at alzheimer's he's one of the world's leading alzheimer's researchers and we just finished grand rounds here at cleveland clinic and we're going to be doing a little q a on this radical new approach to rethinking the brain and rethinking alzheimer's and showing that actually we may actually have a way to actually reverse alzheimer's especially early on so so in your in your grand rounds you really got into this concept that the the brain is very plastic that it can change that it can shift and it actually can adapt to its environment for good or for bad and that there's insults that happen that cause it to go down a path of degeneration but there's also inputs that can happen that can actually reverse that process and you you presented some amazing cases of patients who actually had early dementia that you implemented a whole series of interventions based on functional medicine principles of treating the system not the symptoms and you saw radical changes in recovery and so um how many how many patients have you run through this this protocol so they've now been over 100 have come through over 100 patients and what what percent of those patients have actually shown improvement or had reversal right the majority of them so we published the first 10 and then the first ten nine of them improved and one was very late did not we now recognize several different types of alzheimer's disease and they respond differently so some are easier to treat than others and again earlier better and the ones that have specific types or are very late are more difficult out of the over 100 now a number of them are too early to tell and this takes typically three to six months to see a big effect and so some of these are too early to tell but the majority continue to improve so what are the things that you're finding are really going on at the causative level right and then what are the kinds of things we'll get into what are the things that actually work on the therapeutic level right so on the causative level i mean as you mentioned you know this is all about functional medicine and this is has its roots in biochemistry so you can look very clearly at this plasticity balance you can look at what actually happens to app itself the amyloid precursor protein and there are many things that feed into this and they include everything from inflammation as you've spoken about many times nf kappa b activation in particular activates both the beta and gamma secretase that cleave the app to give you the quote for bad guys the ones that are on the side of the pulling back is like an inflammatory transcription factor that absolutely so you when you have that inflammation going on you are actually putting yourself on the wrong side of the app plasticity balance and then when you can improve that inflammation you're putting yourself on the right side so what we find is that the type 1 patients inflammation seems to be the major driver for this and we want to address that but of course we want to understand not just how to improve the inflammation but to understand what's causing the inflammation to begin right is it external what you're finding in terms of alzheimer's is driving some of this inflammation because you don't want to just take steroids or take an anti-inflammatory which haven't really been shown to be effective so so you don't want to try to just get rid of it without knowing what's causing it and so the common things we're causing we're seeing is that in fact some of it's external some of it's internal the internal drivers are what you've talked about a lot glycotoxicity so we call this type 1.5 because people who have and the reason for that is because they've got both the inflammation and the atrophic part so in fact if you withdraw trophic support from neurons what do they do they start making amyloid so it's a downsizer it's a programmatic downsizer very interesting so you mean sugar and sodium in some resistance so you now if you now the insulin resistance gives you the atrophic part and the glycated proteins cause the inflammation that gives you the type 1 part so you get this combination of type 1 and type 2 which is why we call it type 1.5 so sugar is a big cause and i think you know just as you've pointed out many times the sugar in our diets is giving us a lot of our illness and then of course anything that trans fats that also do you know inflammatory processes and then external inflammagens so we're finding a number of people who have exposure to mycotoxins this is turning out to be a relatively common cause of the underlying problem and a big problem because you've got a mold and then as dr shoemaker has shown it's 30 different things in the soup that we're all breathing it's not just the mycotoxins it's the fragments it's the mycobacteria it's the inflammations it's the volatile organic compounds on and on and on we're looking at toxins we live in a toxic sea that's absolutely right and so you need to know what people does that really affect so we want to check people's hla drdqs to find out are you in the group that is sensitive as shoemaker has shown over the years and interestingly almost all the ones who have that type are in the dreaded or in the highly biotoxin sensitive group so it really fits very much with his model and then of course as you know there's that in inhalation alzheimer's you're talking about which is really based on these inflammatory response systemic inflammatory responses exactly and so it seems that you've got both the inflammatory response where this is really about your response to it but then others who don't have a dramatic response but they therefore have more exposure to the toxin itself and depending on whether you've got more in inflammatory part which gives you more of a type one look or more of a toxic response which gives you more of a type three look these are two different types of patients depending and again so what you're saying basically it's just because you say someone has alzheimer's doesn't mean you know what's causing it exactly and it doesn't really help you figure out what to do about it unless you drill down into the sort of details of what the issues are that are creating imbalances right that's whether that's toxins or it's diet or various factors mold right so this is why i was saying that you shouldn't put a period after alzheimer's disease you should say alzheimer's disease due to blank blank blank you know what are all the things that contribute and that's what we've been interested in to find all the contributors and then to address each of them again very much like a functional medicine approach you mentioned toxic are you finding these patients have heavy metals or other exposure to toxins how do you deal with that so we absolutely are so we find as i mentioned the mycotoxins and the volatile organic compounds and things like that and then others yes and we interestingly we've had a number of people who will come in have pet scans classic for alzheimer's disease classic presentations for alzheimer's disease evaluation elsewhere that says okay you have alzheimer's disease nothing we can do about it but when we look more carefully we find just what your 2007 book suggested that some of these people do indeed have high mercury levels now the majority do not but some it is absolutely a critical contributor yeah and then we've been typically treating them um with the kind of classic uh cube sort of approach with the you know increasing glutathione and things like that helping the body detoxify helping the body detoxify and as you know it takes a number of months but these people you know clearly improve and we look at also you know how much is inorganic how much is organic that sort of thing so you're finding insults like glycotoxicity like mold like heavy metals any others that are that are jumping out as causative factors yeah so and again people who um are you know long-term uh trophic withdrawal people who are walking around with low vitamin d low vitamin b12s so that may not be what's causing it maybe what you're missing like it may be not an inciting factor but like but it's a contributing factor so that's where the type 2 comes in so if you simply again you take the cells you withdraw their trophic support they will begin to make amyloid as part of a downsizing so there are toxic insults they're inflammatory insults but there are also trophic withdrawals that contribute directly to this and you need to methylation defects methylation defects common as you know high homocysteine very commonly associated with 12 folate ob12s low folates these are all contributors and what else can vitamin d you're talking about that and vitamin d absolutely zinc and copper and zinc and one of the things that we've looked at is the copper zinc ratio and of course dr george brewer from michigan has spent his career looking at this ratio of copper to zinc and showing that high copper low zinc is often associated with dementia this was published by others as well and that correcting that can be helpful in number of people and how are you correcting that typically we use uh the brewer protocol which is typically you know zinc picolinate a small amount of manganese as well some vitamin b6 and acetyl cysteine so pretty typical protocol for reduction of the copper increasing of the zinc high dose of ascorbate yeah it's very interesting you know the the the whole concept of dementia is that a metabolic encephalopathy right it's sort of a it's a common pathway for many different brain insults whether it's autism or alzheimer's i often see the same pathologies at either ends of the spectrum right and in fact even in psychiatric illnesses carl pfeiffer looked at this years ago looking at these same things of copper zinc ratios and all these various nutri deficiencies and i think the problem has been that everybody wanted one thing and so in fact as you know now there are many different microorganisms associated with alzheimer's disease especially in biofilms so everything from p gingivalis to hsv1 to spirochetes borrelia burgdorferi you can go on and on and on all of these pathogens that are associated and each time they say well this is the cause of alzheimer's well in fact we're breaking coke's postulates here and yes we're saying it's not just one thing there are many different things that you can get in your brain so if you've got a problem with your oral brain barrier or if you've got a nasal issue and you've got chronic inflammation through that and interestingly for years people have said alzheimer's has something to do with the nose because it's the ryan encephalon you look at the pathways it's clearly nasally related that's been written about for years and yet it's not clear what's causing it well now we're starting to see this and that's one of the reasons for iad so these people are being exposed to chronic inflam inflammation that's coming in through the nose yeah and then of course gut is another one um and obviously you've written how does the gut play a role in the brain dementia the gut is playing a huge one we see a number of these people have very clearly leaky guts you know lps antibodies um they've got hscrps and some of them interestingly not all they've often got sens sensitization to gluten some to other grains and things like that so again we try to get them on more of a fat diet just the sort of thing that you've recommended over the years it's fascinating i just recall a patient i had one of the first patients i had you know probably 12 15 years ago who had early dementia and we just did a functional medicine approach around he had apoe4 homozygous he had methylation snips mthfr homozygous he had years of irritable bowel and high levels of inflammation his gut not just sort of irritable bowel but kind of crossing over to inflammatory bowel he had lived in pittsburgh at very high levels of mercury and had a mouthful of fillings and we didn't and he had very high levels of homocysteine in methamphetaminic acid and we basically addressed all these factors and his brain recovered it was sort of a shock to me and then i called the neurologist like how does this happen how do you see people's scans improve and their neurocognitive testing improve and then objectively get better and subjectively get better sort of a shock yeah this is a major paradigm shift right absolutely and i think we have to get rid of a lot of our old ideas that this is untreatable that there's only one thing that's going to ultimately cause this you know that we give a pill for it this is something where there are multi-factors we need to understand all of them and then we need to address all of them one of the things that terrified me uh in your talk was when you mentioned that statins seem to by a very clear mechanism promote a type of amyloid process that leads to dementia can you kind of go into that and explain what we're doing with this and yeah and of course uh for some people you know statins have been presumably helpful although i think you know more and more people are looking for alternative ways to improve the the lipid profile so what we found we we screened every fda approved drug for its effect on this plasticity balance where we measure this biochemically by the ratio of app cleavages to the memory peptides or the forgetting peptides essentially as we think about them and interestingly the one out of all the fda approved drugs that gives you this the dementogen uh uh signature was statins and interestingly the one that did it the most was the statin that had already had to be taken off the market because it had so many side effects so cerritos yeah so and that would give them muscle problems and things like that yeah so um so arc yeah so our concern is you know it's well because the effect on the mitochondria this was a totally different effect though this was the same different effect this is an effect on the cleavage of app not even specifically on amyloid but on the way and the app the amyloid precursor protein gets cleaved especially to make one fragment which is called c31 which is one that induces programmed cell death so basically you're saying statins affect app in a way that leads to programmed cell death and sort of accelerating dementia that's a concern as you know many people who take statins will say oh yeah absolutely it affects my memory should we be screening people for apoe4 who are taking stats we don't know whether it's worse than apoe4 but i think you're you're right that we want to be sure that these people need the statins and we want to look at alternative ways before we ever introduce the statins so in your paper reversing cognitive decline right you talked about different kinds of diets and ketogenic diets and and fat in the brain can you kind of go into that a little bit because on the one hand we're talking about you know statins causing it and low-fat diets may be contributing and can you kind of explain of course what you're finding about that absolutely and we look carefully because as it's been pointed out repeatedly by by you by david perlmutter by others low cholesterol is associated with brain atrophy so the last thing we want to see is people with cholesterol especially cholesterols below 150 are concerning to us total cholesterol total cholesterol yeah now obviously there are many you know more nuanced ways to look at cholesterol but we worry about people who are low fat we worry about people who have low cholesterol and absolutely this is a problem so we want to get people on mct we want medium triglycerides which is actually a saturated fat exactly we want to get people to have saturated fat and you know has been pointed out this is heresy right right now saturated fat for treating dementia so which organ are you going to pick your heart or your brain or does it matter well yeah and the hope is that you're going to do well with both right right yeah so i mean it sort of goes to the concept of is there one diet that's good for your brain and one that's good for your heart and when it's good for cancer and they're all different so you have to pick your disease or is it really that there's one way of eating that can help support all these uh diseases going away and i think the latter i think we're to you know certainly uh you know understanding lipid biology better is going to allow us to do the right things for the heart and the brain at the same time so when you when you were writing that paper you mentioned ketogenic diets what's been the thinking behind that and actually the reality is although i didn't put it in the paper we suggested that people read your book actually uh on the blood sugar solution or also read joel fuhrman's book if they were interested in more of a vegetarian style uh and obviously we're getting better and better uh with understanding and obviously you've got the new book uh eat fat get thin which you know changes even further some of the dyes i think we're getting better and better about understanding what is the best diet for the brain and absolutely the key to this is changing from a carbohydrate-based diet and to a lipid-based diet that and that seems to be the best for the brain so you know we're here at cleveland clinic and we've been having conversations about research and you know one of the challenges that we've found is that is that much research is just looking at one disease with one variable right but now we're talking about collaborating on doing research program that looks at maybe 100 things right or 500 things right um how is that changing the model because we're all you know the randomized control trial was this one variable one outcome and it's how does that how do we reframe research around this concept and it's fascinating to me that physicians for thousands of years have been dealing with these incredibly complex organisms right and then here's you know you've got your 3.3 billion base pairs and that's just the beginning you know you've got your epigenome and your proteo and all this and then they're saying well let's just fix one thing it really doesn't make sense and i think in years gone by when we didn't have the ability to look at these 100 or 500 you know you couldn't do a whole genome screen then you had to do that you didn't have any other choice but now we're able to look at this we're able to look at you know we can tell you what your hippocampal volume is percentile-wise and we can tell you you know what you know what your entire genome shows and all these sorts of things so absolutely when we take advantage of that we get better diagnostics we get better subtyping we get better ability to make it you know to improve things and that's exactly what we're seeing especially in chronic illnesses and especially with early dementia and early pre-dementia so what's it what's overwhelming i'm sure for many viewers is that how do we then take this and operationalize it how do we as physicians or practitioners apply all these variables clinically and how do we intervene with our patients to effect change and you know if you're a patient or someone listening who's actually concerned about getting it or has someone in their family who has it how do you begin to kind of address this uh and and i think if you're willing maybe you could share a little bit about your vision about how we go about scaling this and making this happen right so as physicians as practitioners we need larger data sets unquestionably we need different way to practice medicine we need more interaction with silicon valley we need more computational biology we need more computational algorithms guiding us say okay given all these ratios etc you know why should this be restricted to derivatives on wall street right right right let's make people better using computational biology we need a functional medicine we need functional medicine taught in the medical schools when you and i came through medical school uh you long after i did came through i mean it was we were never taught this you know it was all about get that drug find that drug and it was all about what it is what's the diagnosis instead of why it is right so we need to change all these things and i think a large part is going to be to be able to have algorithms where you can say okay what type do i have whether you what are all the contributors to my congestive heart failure to my alzheimer's disease to my parkinson's and to address all these things and that is where functional medicine's going yeah so to have the first center here at cleveland clinic is going to be exciting this is hopefully a model for the rest of the world it's great it's very exciting to have you here dale the future is very bright for our brains it seems i hope so i think we're in like things are going in the right direction great well thank you for joining us thank you so much and look forward to collaborating and thanks everybody for watching and uh thank you more to come thanks mark

Channel: Cleveland Clinic

Views: 24,275

Keywords: professional development, grand rounds cleveland clinic, cleveland clinic grand rounds, functional medicine grand rounds, mark hyman md, functional medicine, grand rounds for doctors, functional medicine mark hyman, mark hyman md youtube, alzheimers disease, dale bredesen, dale bredesen reversing alzheimers, dale bredesen the end of alzheimers, dr. dale bredesen, dale bredesen md the end of alzheimers, dr. dale bredesen alzheimers, interview with dale bredesen

Id: u97JEBaDvgY

Length: 19min 22sec (1162 seconds)

Published: Mon Dec 28 2020