Doctor explains how Alzheimer's Reversal is Real-with Dr.Bredesen | The Empowering Neurologist EP130

what our research showed is that it's essentially it is a cha it is an insufficiency just as you would have insufficient blood flow to your heart it's an insufficiency and that in the equation there are two things in the numerator and two things in the denominator in other words anything that's inflammatory is driving you toward alzheimer's pathogens leaky gut well all the things you've written about [Music] hi everybody i'm dr david perlmutter welcome again to the empowering neurologist we have a very exciting show for you today and you know you may hear me say that quite a bit because i think a lot of our shows are really exciting but today is really going to be quite special you know we all can probably name a few cancer survivors but can you name an alzheimer's survivor i bet not and i think the reason for that is that mainstream medicine offers up only simple ideas as it relates to alzheimer's and by and large we don't have anything in the mainstream approach that has any meaningful effect on the progression the inexorable decline of these patients in terms of their cognitive function and ultimately taking their lives it's now been estimated that alzheimer's is the third leading cause of death in america and that's a pretty astounding metric isn't it well exciting news there are now alzheimer's survivors and these are patients who are treated under a protocol developed by dr dale bredesen you've heard me mention his name uh many times he's written several great books the end of alzheimer's and then the end of alzheimer's program i had the opportunity to write the forward to that book he has a new book out called the first survivors of alzheimer's that documents the uh in their own words what individuals have gone through what their programs have been like and uh how they've been successful uh at actually turning this around dr bredesen has a new study out that we are going to review a nine-month uh study that had an 80 percent improvement rather 80 percent of the individuals in his program undergoing his treatment protocol improved and you know basically what we'll talk about today is the incredible paradigm shift that has been embraced by dr bredesen and his team such that rather than trying to make patients fit into a specific treatment he customizes the treatment based upon the needs of the patient whether it is reducing inflammation reducing oxidative stress targeting a brain energetic whatever it may be and he's doing so with great success let me tell you a little bit more about our guest dr dale bredesen dr bredesen received his undergraduate degree from caltech and his medical degree from duke he served as resident and chief resident in neurology at ucsf and then was a postdoctoral fellow in the laboratory of nobel laureate professor stanley prisoner he was a faculty member at ucla from 1989 until 1994 and then was recruited by the burnham institute to direct the program on aging uh at 1998 he became the founding president and ceo of the buck institute for research on aging an adjunct professor at ucsf then in 2013 he returned to ucla as the director of the eastern center for alzheimer's disease research the bredesen laboratory studies basic mechanisms underlying the neurodegenerative processes and the translation of these knowledge this body of knowledge into effective therapies for alzheimer's and other neurodegenerative problems leading to the publication of over 220 research papers he and his group developed a new approach to the treatment of alzheimer's disease and this approach led to the discovery of subtypes of alzheimer's disease followed by the first descriptions of reversal of symptoms in patients with alzheimer's and also mild cognitive impairment as we're going to talk about that recent study his upcoming book and all the things that he's involved in when we get to the interview which is right now well hello dr dale bredesen how are you doing i'm doing great how about you david i'm i'm doing well i mean we we have to sound a little bit formal here but uh you know truth be known uh we'll let our audience know we've known each other for a number of years and i think back of the wonderful hike that we had together on stuart island right many many years ago the well wasn't that it was 2017 i think or 19 anyway but the four of us pardon me in the pre-pandemic era yeah bc before covet you've been a busy busy man that's for sure and you have a new book coming out called the first survivors of alzheimer's you know you've often said that we all know a cancer survival survivor but who knows an alzheimer's survivor but you are absolutely changing that aren't you absolutely and that that of course is the goal and i think that you know that when you get at the root cause and you have you and i have talked about this for years when you get at the root cause of the problem then in fact you get improvements that continue and so you've got people who are surviving we have people now who are over nine years on the protocol uh who would likely be in a nursing home or have passed away by now who are gainfully employed and doing great wonderful things and so it's just it's so wonderful to see that and i think well you know i i was so excited to get your email a couple of weeks ago uh not even now with the publication of your your new study and we definitely want to unpack that what you know demonstrating uh that 80 percent of the individuals who engaged in your protocol uh demonstrated improvement during after the completion of the the nine-month study but i want to start off with a little bit of a a story a bit of a metaphor and let you run with it because i know you will a guy walks into the office and doctor's office and he says you know my feet are hurting and the doctor says well what are you doing he says well i'm walking like you told me five miles a day and uh the doctor said well what kind of shoes you're wearing and the patient says oh i'm not wearing shoes so the doctor says you need a pair of shoes and he gives the patient a pair of shoes and the man cannot put the shoes on and the uh he says well i wear a size 11 these are a size nine and the doctor says well we've studied ten thousand people and the average shoe size is a nine and therefore we're gonna make this have to work for you now i think our viewers probably scratching their heads right now but you know darn well where i'm going with this so let me let you take that and run with it yeah you know so this is uh what's called a pro crustian approach as you know uh and you know procrustes would actually you know chop people's legs off to make them all fit the same size bed so it really is hilarious uh unfortunately sad in the neurodegeneration area so as you know we've spent the last 30 years looking at what actually drives the problem and the real surprise is that there's a number of things we initially found 36 but there are a few more but the good news is it's not thousands um it's dozens and there are things that as you know you know various uh pathogens and various uh toxins and these sorts of things and so yes absolutely each person number one is different than the next person so you really have to get the fingerprint and the and this is really uh as jeffrey blanda's point there's really a systems approach you're looking and this is the basis for functional medicine so you're looking at what drives it and then the other thing of course is you're looking at what's most upstream i actually had a discussion with my mentor stan prisoner years ago at the buck institute and the idea was at the time we're going to get rid of all the amyloid and once we do that people will have 20 years with no problem they want to be on any drug at all because once you get rid of that amyloid that's what's causing the problem and therefore you'll be fine well it turns out of course amyloid is not what's causing the problem it is a mediator and interestingly it is a prionic mediator of the problem and therefore is just as you indicated you need to know why the person is actually having problems with their feet instead of just giving everyone the same thing which may which has absolutely nothing to do with the original problem well in in our modern world uh we would like to think that we have identified the cause of alzheimer's disease uh there whether it's a bioenergetic defect or it's a mitochondropathy or mitochondrial dysfunction or it's toxic uh whatever or even infectious but i think you've made it very clear that we can take many roads to get to rome and that oftentimes multiple factors conspire to amplify the the detrimental effects of each other organisms can enhance inflammation which can enhance free radical media stress which can antagonize the the trophic effects of insulin you name it and that it is beyond myopic or simplistic to think that everyone is going to use a cholinesterase inhibiting drug and derive some benefit not just because it's not unique for them but because the research shows that that approach doesn't even work you know there was a lot of excitement recently with eli lilly's new monoclonal antibody donepemab that it was so great that the stock of eli lily went up billions of dollars with an announcement that it actually slowed the decline of alzheimer's by a third or 32 percent right it that's not what we're looking for here we're looking for is what dr dale bredesen is demonstrating in his research that we're slowing the decline is one thing but keeping people level is another but the home run is getting people to actually improve and you've done that right and that's and that's the whole key and i think you know this is the semantics of success in this field as you know unfortunately and so here's a drug that did not make people better that did not even stabilize people but the fact that it slowed the decline by slightly less than a third was getting people all excited but of course in one of the husbands of one of the patients said to me years ago the pharmaceutical companies are looking for something that slows decline he said when you have a wife or a husband who has alzheimer's disease especially in the late stages that's the last thing you want that was such a sad thing to hear from him so the reality is we want people to get better and more importantly we want them to stay better we want that to continue for years instead of bumping up and then just going right back to decline so that's the goal and that's what we saw in this trial so this is why we were so very enthusiastic and as you indicated about 80 percent of the people actually got better they improved their moca scores they improved their cns vital signs neurocognitive index which is an online very sensitive test for changes in cognition they improve their aqc which is a change score which looks at does the study partner or spouse think that they're doing better in various areas or worse in various areas they actually had better mris than even people who are stable so that much better than people who had a natural decline with alzheimer's disease but even the people who had mild decline with aging they did better than those people so in all parameters these people did better by attacking the things and identifying the things that were actually causing the problem it is a real paradigm shift what you're proposing here and that and certainly can be extrapolated well beyond dealing with alzheimer's disease in other words a whole approach to dealing with illness in the first place uh in that you're not trying to get the patient to fit the the treatment quite the opposite and you know you've spoken at length about our need to gain better understanding about the needs of that individual and uh you know again that would extend far beyond just the the framework of alzheimer's but you know let's just unpack a bit and where do you want to start do you want to start with energetics so why don't we start with the notion that there is a bio energy effect energy defect in the alzheimer's brain that may predate the onset of clinical symptoms by 20 even perhaps 30 years it's a great point david so let's start with what is this disease that's been the biggest problem you know from a research standpoint the biggest problem has been we understand what covet 19 is it's a virus we have the sequence we have a sequence of a bunch of variants we know what this is so it's just a matter of going after it the way we know you can go after a virus with alzheimer's it is a fundamentally different problem people have whole ideas it's it's herpes simplex related it's type 3 diabetes it's reactive oxygen species it's tau it's amyloid just go down the list there are dozens of theories none of them has led to an effective treatment so what what our research showed is that it's essentially it is a cha it is an insufficiency just as you would have insufficient blood flow to your heart it's an insufficiency and that in the equation there are two things in the numerator and two things the denominator in other words anything that's inflammatory is driving you toward alzheimer's pathogens leaky gut well all the things you've written about anything that is toxic driving you toward alzheimer's and then the denominator so anything that's low on the energy side just as you mentioned and anything that's low in the trophic side so nerve growth factor bdnf estradiol nutrients vitamin d things like that all those so those are the four big groups and then within those there are lots of ways to get there just as you indicated you can get there through sleep apnea you can get there through some vascular occlusion you can get there through some various pathogens sinusitis but those are the big four things and we need to get that energetics and that really means four things we need blood flow and again again so things like exercise so helpful and having less vascular disease so helpful we need to have oxygenation so we need to check our nocturnal oxygenation so critical then we need to have mitochondrial function as you've talked about so many times and then ultimately we also need to have something for the mitochondria to burn so in this case we need that ketosis and we need to have the ability to flip back and forth we need that metabolic flexibility that aida has pushed i have to give her credit for that she has pushed metabolic flexibility from day one as a critical determinant of cognitive decline and i think she's absolutely turned out to be right and you know as i've told you before you know many many years ago we first started this research in the lab she said okay it's great yeah you can transfect cells and you're going to have them express your proteins of interest and all this she said you know but when you when you finally figure this all out it's going to have something to do with diet exercise sleep stress you know basic things i said no no we're going to find one molecule and it's going to be one region one domain of one protein and we're going to get a drug for that and everyone's going to be cured and of course i should have listened to her a couple of decades ago because she was absolutely right it does turn out to be this very interesting phenomenon of an insufficiency in a subsystem within the brain a plasticity network and just as you indicated it's the same idea for parkinson's in that case it is a motor modulatory sub network it's the same thing for als in that case it is a motor power sub network same thing for macular degeneration all of these things have their own sub networks and each one is under supported for the demand placed on it when you have this neurodegenerative disease so you're absolutely right we should be able now with the unique biochemistry for each of these to go in and do the same thing we've already started this now with people with macular degeneration so we're very enthusiastic about that but first thing is to you know get this uh recent paper that we that we posted recently in med archive get it published in a peer-reviewed journal and then we've already started planning a larger randomized controlled trial just to show the same thing we've been seeing in anecdotes and now more recently in this trial this proof of concept trial clearly there are um parts of the story that throw a a bigger net than others i mean not everybody has had mycotoxin exposure about lead cadmium murky aluminum or arsenic i mean but they're all important i'm not i'm not belittling any part of the program but some of the bigger players i think would be bioenergetics you talked about uh glucose and ketones and and and the use i mean the role of insulin within the brain for example why i mean is it reasonable to assume that uh the adoption of a a more comprehensive integrative holistic functional approach could be saltatory on the part of mainstream physicians with respect to let's say the bigger players uh you know we've known for years that there's an increased risk of of alzheimer's in type 2 diabetics hence the call to get your blood sugar under control but it seems to me that even today that neurologists uh really you know push the alzheimer's patient to the endocrinologist to manage that part of the story because it seemingly has no relevance to the notion that you are simply an acetylcholine deficient or have accumulated amyloid in your brain what is like where i'm going with this is what would it take just to get the foot in the door with some of the bigger more leverageable concepts that might indeed have an impact like um like blood sugar insulin sensitivity you know this is such a good point and what it really tells us is that this is an internal medicine condition as much as it's a neurological condition so there are a couple of ways to go and i know i've i've upset some people by suggesting a couple of things one is either the neurologist should be managing the patient with an internal medicine physician who is trained in this sort of functional medicine which would be one way to go and of course neurologists tend to want to say well alzheimer's patients are neurology patients we're not going to be having them treated by these other we're going to use our next drug which is unfortunate and the other one which i know upsets people is i i've suggested that that that universities create a department of modern neurology so that there is there are two departments of neurology the department of neurology which is the classical stuff that you and i studied years ago where you know you're studying things like charcoal and then there's the the modern neurology which is actually bringing in some modern concepts concepts of precision medicine systems medicine functional medicine all of these sorts of things now again the problem is that this has become much more of a political issue it's a turf issue you know this is what we do and we actually get grants for doing this and we make agreements with drug companies to test the next drug well unfortunately at some point this becomes negligence this is a ultimately a very a criminally negligent situation once you have published data showing that you can make people better but people are actually ignoring published data you know there's a legal term for that unfortunately so yes i i completely agree with you i hope there will be a change now as you've seen there are little changes but people don't exactly know what to do with it so they what they say is well just exercise in fact the chairman of neurology at one of the major universities said to me well when we test a drug we don't tell our people not to exercise well that's completely missing the point the point here is not to tell them to exercise or not the point is to determine what is driving their cognitive decline which in virtually all cases has nothing to do with your drug that you're testing now i do think there's going to be a fantastic place for drugs we're actually going to have new targets now that we understand these things that are driving the underlying problem the drugs are going to be helpful i mean for example if you want to remove that amyloid hallelujah but please wait until you've removed all the insults that are causing your brain to make amyloid as you know our colleague rudy tanzi along with the late robert moyer showed a number of years ago that amyloid is actually quite a good anti-microbial peptide interestingly has antiviral properties and anti and anti-fungal properties it is a very interesting molecule and really has the properties of a channel so it can destroy things with membranes essentially and so you're making it for a reason and let's get rid of all the reasons that you're making this and then the idea of removing it is a fine idea i think the idea of using dynamab or atticanum app at the right time makes much more sense couple thoughts come to mind first um the donenomed study interestingly in the treated group demonstrated measurable loss of tissue atrophy if you will in comparison to the placebo group and i think the the write-off was oh well that's because we took away the beta emily it was thought that you know if you the the brain total brain load of this protein is about four and a half grams so it's hard to imagine taking four and a half grams of a substance out of the brain would have explained uh the degree of uh change that was seen but but i i think you make a good point i mean you know mainstream has really kind of latched on to the it was the acetylcholine hypothesis and now it's the amyloid hypothesis uh to the you know the exclusion of the data that is indicating exactly what you've said and even prior to rudolph tanzi uh ruth atsaki in england showed co-localization of beta amyloid ii herpes simplex indicating exactly what you said the amyloid is a response element it's an anti-microbial peptide that you know uh the enemy of my enemy is my friend right so it's there uh it's responding and could there be downsides to uh to eliminate one wonders i mean in the early uh uh monoclonal antibody trials you'll you'll recall that you know patients in fact did decline more rapidly with respect to cognition it was certainly worrisome now with this latest iteration there's a bit of a slowing of that decline but you know that that may be getting you to first base we're we're looking to get people around around the horn as it were back uh you know to score some points here and uh again it's all about finding the shoe that fits that person who's sitting in your office with the sore feet absolutely you know you brought up a good point people do backflips is you know to try to make it all fit as you know with adequate map it was actually turned down by the fda and then the an internal statistician who's working for the drug company said oh wait a minute i think it might have worked in one at one dose in one trial i mean come on so as and as you pointed out there was actually a decline in the volume well it turns out stuart lipton and you know stuart has done some beautiful work and is the one who developed originally developed to the idea from a manten and stewart found that when you look at the brains at when you give these antibodies it actually causes inflammation yes this is part of an inflammatory response you're going after pathogens and things like that so no surprise that you are actually going to create further problems by using these antibodies so again you want to do it at the right time and interestingly great research and then the conclusion as with so many of these things was backwards so the conclusion was okay let's now develop a second drug we give with the antibodies to try to inhibit the inflammation that the antibodies cause i mean this is just such backward thinking we want to look at what's actually driving this and there's some some nice work out of ucla years ago and continuing on showing that if you simply look at your peripheral blood mononuclear cells so you're looking at the ability of these monocytes and essentially macrophages blood blood-borne macrophages to chew up beta-amyloid to take it up phagocytosis everybody with alzheimer's has a reduced ability to do that and when they actually go on the protocol we just publish that actually comes back to normal and he measured that years ago very exciting so your body is saying we don't want to get rid of this stuff it is an anti-pathogen thing that we've now done this is as you know part of your innate immune system so you're not trying to turn off the innate immune system and unfortunately just as people die from covet 19 from cytokine storm alzheimer's disease is to some extent cytokine drizzle you've got this chronic activation of the innate immune system and until you get the adaptive system working well you clear out the problem you quiet down the innate system you're going to continue to make the beta amyloid that is part of that innate system and it is going to trigger the phosphorylation of tau and trigger the reactive oxygen species you referred to and trigger the downsizing of your brain and all the things that we are trying to avoid so absolutely getting to the upstream is the key well you know as it relates to then this balance of the of amyloid doing what it could do which is positive versus the the detrimental pro-inflammatory issues i mean i i think that there are variables we can deal with right now we can up regulate uh insulin degrading enzyme by becoming more insulin sensitive through dietary means and as such you know recognize that the the this enzyme that degrades insulin is also involved in the degradation of beta amyloid so let's um let's look at diabetes for a second because you know i'm not going to throw the type 3 diabetes and hang on to that but i think it does throw a pretty large net in terms of energetics in terms of trophic issues in terms of glycation proteins and inflammation in terms of what i just mentioned in some degrading enzymes so again um it seems like that's a big lever that we could be pulling yeah this is such a good point i would argue that you're right this is likely to be the most common of all so when you look at these people you know the strange thing you look at this and you say gee it's a metabolic disease no it's an infectious disease no wait a minute it's a toxic disease now wait a minute it's a genetic disease and so that's the that's the key how do you understand the entire picture and this is why i think the idea that this this all affects the same network tells us a lot and the most common thing that we see is exactly that people who have high homa ir people who have high fasting insulins who are either on their way to type 2 diabetes may have pre-diabetes or not quite be there yet uh but are on their way and have insulin resistance because what is that that's 80 million americans exactly so and what does it do it's interesting you can go back to that equation we talked about earlier what does it do well guess what it affects the energetic part it affects the trophic part because now you don't have the same sensitivity to insulin which is a critical growth factor when we used to grow brain cells in a dish we always had to include insulin to keep them alive well guess what it also is toxic you get things like glyoxals in the brain guess what it's also inflammatory because it now non-enzymatically glycates hundreds of proteins and of course we measured as hemoglobin a1c but it's hundreds of these proteins so if you look at it it actually ticks all the boxes that are giving you an increase and as you indicated 80 million americans so so incredibly important and you know one of the biggest problems i think we face is that we talk about mild cognitive impairment we've come at this backwards because alzheimer's was identified first and we've worked our way backwards to mci sci well think about it this way when you have activities of daily living affected and you now have true alzheimer's that's been 20 years in the making and so this is like widely metastatic cancer so we really should be calling people who are in the pre-symptomatic phase pre-alzheimer's people who have this minimal subjective cognitive impairment that's early alzheimer's disease so you've got about a 10-year window there treme people understood oh my gosh this is early alzheimer's i can jump on it now all of those people get better what we call mild cognitive impairment is late stage alzheimer's disease and what we call alzheimer's disease is really end stage alzheimer's disease so if people understood yes let's change the nomenclature so that we can understand this is a long process you can get in early but that's absolutely going on when you're thinking oh yeah i'm probably okay well beyond the nomenclature let's talk about the lexicon because i think there's a term you may have added to the lexicon which is the cognoscopy did you invent that yeah i mean i just said it because it's it's easy for people to think oh colonoscopy don't forget the cognoscopy so i've been told not to use the word it's a horrible ugly word but i think it's terrific because you're advocating an annual cognoscope i tell us what that means and why you think we should have them yeah so the point is that so many of us uh you know that we're this sneaks up on us as you well know this sneaks up on you and so you think well is this just aging and even your doctor unfortunately will tell you oh yeah you're having a little problem but it's just aging no senior moment senior moment i've heard that many times so the reality is you should get checked out to see because as you begin to change in fact that doesn't happen for no reason as you well know so there's a tremendous amount you can do and you indicated you know dealing with pre-diabetes dealing with ongoing inflammation and metabolic syndrome and gut issues these make huge changes and we hear all the time people say you know i just had a little bit of subjective cognitive impairment oh my gosh i'm doing so so much better so a cognoscopy is simple it's three simple things number one get a set of blood tests that tells you what are your inflammatory markers what is your home ir where do you stand with your insulin sensitivity you know what did you have toxins on board do you have a reduction in things like vitamin d and hormones and things that are critical there second thing is to get a simple online cognitive assessment easy to do you can do it in about 30 35 minutes and you can see you know am i having issues and if there's a question repeat it in six months and see is this a progressive problem and then third thing is actually optional if you're truly asymptomatic and you're scoring well you don't need an mri but if you're not scoring so well or you're not asymptomatic then what you want to do is have an mri and please include the volume metrics it's easy to do you can do it you know post mri from depending on how the mri was taken and it will give you an idea where do you stand with your gray matter volume where do you stand with your hippocampal volume and you've pointed out for years how critical hippocampal volume is with respect to what is your what is your fasting glucose and where do you stand within a pre-diabetic state as your glucose goes up your hippocampus shrinks down same for cortisol cortisol up hippocampus down you know this isn't a this isn't neurology rocket science uh this is available i mean we can know our our heart rate our fasting blood sugar our ketone levels at home not in the doctor's office we can check our uric acid levels we can perform the online cognitive assessments we can determine the quality and quantity of our sleep what stages of sleep we're in our oxygen saturation it's all available now at home via wearables and it's it's a new age the question is uh you know i just think people need to see this amalgamation of data in terms okay what does it mean where am i going and beyond that okay what can i do which areas of my program need work i mean do i need a full on ketogenic diet or not because i think it's fair to say that while to focus on that ketogenic diet may be a good thing for neuronal energetics mitochondrial function it may not be appropriate for everyone so i think you know the beauty of what personalized medicine is all about is teasing out which levers are the most important for that person i.e which shoes are going to fit you know dave i think this is such a great point because things have changed tremendously just in the last few years with wearables and with social networking and i actually think that wearables in social networking are going to be two major cogs to the end of alzheimer's to making this a much much less common disease which it should be this is basically a disease because we're not we're not looking and we're and we're eating the wrong stuff and doing the wrong things we're giving ourselves this problem and so being able to know hey what's my heart rate variability hey wait a minute i must be under a tremendous amount of stress i got to look into this further or hey wait a minute my nocturnal oxygenation is dropping down to 82 percent while i'm sleeping wait a minute something is really wrong here i better get this checked out and then interacting with other people as you know april e4 dot info great thing that was started by julie g who's a who's a 4-4 herself and is doing very very well now uh these sorts of things sharing information and saying hey these are critical i think that's going to push some of the physicians to say you know we really do need to look at these things because they are critical and they're the things that are actually going to help us reduce the global burden of dementia you you mentioned covet earlier and uh you know i guess no interview could be complete or a conversation i could call it interview without looking at covet through the lens of what that might look like in the future as relates to your interest your area of neurodegenerative diseases about a week ago in the lancet was a a report about the significant number of people who are left with various types of neurologic dysfunction and then earlier in the year we saw a really well-designed overview in jama a gemini network i think it was looking at the various mechanisms whereby kovid seems threatening to the brain we now know that there is actual evidence of entry of covid into various parts of the brain and some of these mechanisms include excitotoxicity nmda stimulation a kinurenic acid pathway with quinolinic acid being produced uh increased inflammation as evidenced by increased levels of you know interleukin-1b il-6 il-10 tnf alpha the vascular issues the blood-brain barrier disruption etc but when you take a step back um many of the things i just mentioned are implicated in the work that you do so what i'm what i'm getting at is might we have set the ball in motion for a lot or might we but i mean has the ball possibly been set in motion by this uh underlying viral illness in terms of future alzheimer's risk this is a great point you know and i do think if there is a silver lining in this pandemic cloud then it is that we will be more proactive in prevention and i do think anyone who's had covet 19 should be on active prevention of cognitive decline please get a cognoscopy please get on active prevention because as you indicated we don't know the future and you when you actually look at the brains as you indicated you see micro thrombosis you see micro hemorrhage you see inflammatory cells there's even the report of megakaryocytes as it being a question of one issue um they're of course the cytokines one is as i said cytokine storm the other one is cytokine drizzle but it is the same phenomenon in in which your innate immune system is activated beyond your adaptive system you have not succeeded in clearing part of the adaptive system's job is to turn down the innate system okay i will take it from here well they haven't taken it from there that's the problem and so absolutely anyone who's had covet 19 should have a cognoscopy should optimize their cognition but also their mitochondrial function because as you know a few of these people have developed parkinson's right after the covet 19. it's very concerning now so far it's not looking the way it was with post encephalitic parkinson's where so many people are coming down but hey one year five years 10 15 years from now we don't know so it is possible that we are faced with future increases increases in what's already very high uh prevalence and and incidence of alzheimer's disease and parkinson's and so i think it behooves everyone to get on active prevention i think that um it's sometimes a little difficult temporally to get your arms around relationships because we don't see them we don't you know we're just seeing the publications over the past couple of years showing increased rates of dementia among those uh who were exposed to the toxins of of 9 11. we know that people were exposed to horrendous amount of toxins uh with the california fires last year and so that you know there may be a significant delay it may have set into motion uh issues related to long-term consequences from prevalence infection i mean and i'm remember research that looked at the uh mptp individuals in 1983 and in southern was southern california or san francisco who uh experimented with the synthetic demerol uh and uh ultimately immediately by virtue of the damage to the mitochondria in the part of the brain that creates the dopamine that is involved in the motor system these individuals developed parkinson's but what's interesting the reason i'm bringing it up not that that's not interesting is that when these individuals years later passed away there was still ongoing microglial in uh activation in other words activation of the immune cells within the brain producing these inflammatory mediators long after the initial exposure the unique or only exposure perhaps that these individuals may have had so what i'm saying is that these events though isolated can set into motion cascades that are feed forward and continue uh to worsen with time and i think that kind of brings us back to the work that you're doing because you're finally recognizing this and stopping it putting out the fire and here's why this is critical this is where the prionic loops come into play so what happens is you have a system that is unfortunately not a homeostatic system homeostasis is great when you have a single goal outcome and you don't require rapid amplification so things like serum ph but when you have a multi-goal outcome for example blood clotting and then and then removing the clot or forming memories or pulling back now you have systems that are prionic loop systems these are just as you said feed forward systems so you can get one insult and then you unfortunately if you're on the wrong side of that equation which is why it's so critical for us to get in early and get people back on the synaptoblastic the making synapse side of that equation then as you indicated here they are years later and the system is still responding to the fact that it's a feed forward system and another great example of course the world trade center first responders were evaluated in 2015 years after the original problem and it turned out that 12.8 percent of them and then actually a follow-up paper a little higher about 14 of them actually had cognitive decline so even though they had a big toxic burden for essentially a couple of days they in fact were still now developing cognitive decline years and years later at a very very high rate so you made a good point the california fires big concern we were all in that polluted air uh for you know a month or so with yes we are ongoing yeah so this is a this is an absolute issue and so yes this is why it's so critical i think for people to get on even though you don't realize at the time okay i'm not having any major problems today please get yourself on the right side of the equation so that you don't have this ongoing problem and it really means that we in trying to treat this need to get people on the right side of that equation to defeat that prionic loop well i i think it's to look at the offsets i mean we can't live in a completely sterile environment our world is certainly very polluted we're exposed to things day in and day out i had the opportunity to spend time yesterday with dr stephanie seneff the discussion of course on glyphosate you know good luck trying to avoid glyphosate that's not going to happen and i i i really as it relates to glyphosate for example i wasn't going to go there but you know it it acts as an aromatase inhibitor i mean amongst the other things it does with respect to the good versus bad bacteria if you will in the gut uh and acting as a metal chelator but even as an aromatase inhibitor therefore uh you know there's some discussion that it may relate to things like pcos uh elevated levels of androgen with decreased levels of estrogens why would i bring that up in a discussion with you yeah it was it's a very good point and of course glyphosate and as stephanie has pointed out it does look like a very good potential insider of als with multiple mechanisms and so it is likely to play a role in multiple neurodegenerative diseases i think the the is most compelling for als but very possibly affecting alzheimer's and parkinson's and other things as well and as you indicated this is a dynamic process this this is not just you know we can just get away from glyphosate tomorrow we all have some degree of glyphosate exposure and in fact uh some physicians have reported that in when people are coming in who are relatively young and very healthy and yet present with als or parkinson's the one thing they often find is very high glyphosate levels so that doesn't prove anything but it certainly makes us wonder you know is this going to be a critical player and absolutely we want to have people on ongoing detoxification because as you said you know we're all exposed to these toxins we're living unfortunately in an alzheimer's soup and so we need to recognize that and we need to continually be detoxifying as well as optimizing our metabolism and the other things so it really comes down to this overall burden that is a dynamic one that we can now address making ourselves sensitive to insulin and making ourselves an active detoxification and healing our gut just as you've talked about for years and years that is such a critical part of this and in the trial uh it's interesting not only did we see the vast majority of people get better but interestingly the few who did not get better you could see why they weren't getting better one of them had very high mycotoxin exposure simply said i'm not moving out of my house not happening i'm not remediating i'm just going to do the best i can with what i have and unfortunately with continued exposure had continued decline no surprise a couple of people they started doing well and started improving and then the pandemic came and they said uh-oh we're staying inside we're eating the wrong food we're not going to do these things we're not going to exercise we're not going to get outside and guess what they didn't do as well you could actually follow them up and then have a slight hiccup at the end there so you know we're starting to see that this is not as mysterious as people have told us oh alzheimer's we don't know what causes it we don't know what to do about it no this is a not so mysterious disease and we can measure the things that are driving this and there's a lot we can do about it well you've you've said in the past that alzheimer's should never have a period after it shouldn't be a person has alzheimer's period right it should always be a person uh may or may not have alzheimer's due to right fill in the blank yeah it's like fever you know dying of fever well wait a minute why did you have a fever same idea why did you have alzheimer's it's like a fever and i do want to just quickly say that the people i worked with on the trial uh dr kat tubes whom you know uh dr ann hathaway uh and dr deborah gordon just absolutely fantastic functional medicine physicians and just did a great job really honored to to have done this trial with them how wonderful to uh take a pause and and call that out that's i love it i love it that's great um so many thoughts come to mind you know when you're talking about um als uh and you know the increased rates of als certainly uh parkinson's as well boy that one's skyrocketing in comparison to where it used to be we'll talk with that in a moment but you know one of the things that uh um was tickled in my mind talking to stephanie cena i didn't really get to ask her the question but she had indicated that here in florida where so much glyphosate is used in sugar and enters lake okeechobee and then filters down through the various river of grass to the everglades and through various rivers just north of us we're having these incredible fish kills as a consequence of red tide incredible overgrowth of cyanobacteria and um known to produce bmaa and i was actually uh how did i know you knew about this because i was reading it in a throwaway article in a in a waiting room while my wife was having a mammogram a couple years ago and i saw your name commenting on the bmaa story a neurotoxin but uh there's so much hey terrible pun downstream effects of these things that we're doing upstream through multiple steps so that we could say well glyphosate is bad because but when we look at you know the various ways through the ecosystem that it affects things sometimes it's difficult to relate it back to growing sugar that now we have higher levels of atmospheric bma which is a neurotoxin it's hard to make those connections and certainly hard to you know to prove them to people who could be in a position to maybe do something about it this is such a good point and so this is why we need larger data sets and you know i should go back to saying also it makes a huge different difference what physician you see we're seeing that this is a lot more like surgery new medicine is a lot more like surgery in that you have to do a whole set of things you have to do it's really a procedure as opposed to just writing a prescription and so it's critical and absolutely this is why when you get these larger data sets you start seeing oh here's a pattern where you've got an increased glyphosate and you maybe have some increase in the homa ir and maybe you have some lipid abnormalities putting all these things together and maybe you have low estradiol with low vitamin d what have you then you can begin to trace these back and as you said i mean there is a tremendous amount of detective work in the past you know we've heard all these wonderful stories about figuring out that things like scurvy oh my gosh what are these people actually dying from and then of course each century they would figure out a treatment for scurvy and then doctors would reject reject it and say we don't believe that it would take until the next century to come again so we're doing the same thing now we're starting to figure out what are all these things where are they coming from and again stephanie cena's work i think is instrumental in understanding all the remarkable effects of glyphosate and how critically damaging it can be and you mentioned the bma of course paul allen cox has done beautiful work on this with his laboratory for years and identifying this as a critical excitotoxin and again what happens though people jump in and say okay if we just take the l-serine that should do everything well we'll see there are ongoing trials maybe it will but my guess is it's more complicated than that but that that will be part of an overall optimal protocol going forward just as specific drugs will be but starting with the appropriate protocol which is for you which targets the things that are actually driving the decline i think that's the way medicine is headed toward being i would say more sherlock holmes ian to for us to understand because this is a you know we're dealing with very very complex organisms human organisms and these things are not simple the old idea that you're just going to write a prescription and it's going to take care of 100 things is really backwards really outdated thinking we can take care of one thing by addressing 100 things you know one of the the powerful tools used in medicine has routinely been uh unique strains uh with genetic uh differences of rodents for example mice the mouse model of alzheimer's disease that has a specific unique genetic uh change uh in in your world then that type of model would not be very applicable correct you know that is a really critical point because we worked with those models we worked with the alzheimer's transgenic mice there are different ones now they're the 5x fad moles which is basically they're saying fad familial alzheimer's disease well that's less than five percent the mice that we worked with were typically app mutants app mutations in humans represent less than one percent of alzheimer's disease so the vast majority of us who are developing alzheimer's develop it in a sporadic sense this is sporadic alzheimer's and it has little or nothing to do with those mutations and yet of course when we test these various theories and these various drugs we test them on mice that only model that rare case of alzheimer's and then we make this leap and say ah this is going to be good for humans and no surprise when it's tested in the clinic it shows that it's not good for humans and you see it with atticanumab and don anumab and you see it with baphinuzumab and gantanarimab and crenazima all these things that we developed with the mice sure in the mice what are you doing you're making them make more amyloid so no surprise taking away what you just caused to happen in the mice makes the mice better but that's not the way the disease works in humans in humans it's because of all these other things including potentially bmaa and glyphosate but it's because of your metabolism and it's because of your hormonal and trophic factor changes and all the things you and i have talked about so it is a fundamentally different problem and unfortunately this is where the animal models have led us astray i remember as a kid sitting at the dining room table and my dad uh kept saying something to me day after day until i memorized he said all disease is either infectious neoplastic toxic metabolic congenital degenerative or traumatic and i had to say it in one breath and if he were alive today i would say guess what it looks like um you know many of these things conspire to together that you know this is multi-mechanistic in terms of certainly well beyond neurodegenerative conditions i mean i think we can look at autoimmunity for example and recognize that the notion of monoclonal antibody to target tnf alpha or whatever it may be as a meaningful treatment uh for a you know the autoimmune disease du jour uh is really again very myopic not really focusing on uh the the fire simply focusing on the smoke or the downstream issues as as it is with uh diabetes my goodness i mean i had the opportunity last year now be longer than that now it was in person a year and a half ago to lecture to a group of mainstream physicians up in new jersey and i asked um what is the goal in your diabetes treatment and uh you know i was getting response like getting the a1c below seven uh whatever you know whatever the metric was and i said what's your go-to treatment to treat diabetes how do you treat it and i heard you know all kinds of drugs mentioned metformin you name it and i said let's let's be fair what happens when you stop that drug what happens to the blood sugar well you know a few days later it's going to go up of course that makes sense that's why people stay on drugs so i said did you really treat the disease then if uh or you did you treat the symptoms the downstream manifestation elevated blood sugar so not that there's not a place for the for the treatment in in the short term or even in the long term as an adjunct and i think you've been very clear over the years that there may well be a place for cholinesterase inhibition and or treatment specifically targeting a beta amyloid but that these are adjuncts these are tools in the toolbox while this multi-disciplinary approach to target multiple inputs is undertaken absolutely and the thing is yes you can help out so but first and we and we think more and more about this as phase one phase two phase three so you know phase one is really let's remove the thing that's causing the problem and it may be as you said maybe mycotoxins but it may be other things it may be metabolic changes it may be leaky gut and often all of the above you know step two is let's build resilience let's get optimized everything let's get you to be insulin sensitive and let's get you exercising get the blood flow get the oxygenation all those things and then step three is let's let's now rebuild let's get you the appropriate trophic support and maybe at some point stem cells will be critical again stem cells currently being evaluated as a monotherapy which is like trying to rebuild a house as it's burning down really doesn't make a lot of sense let's put out one tool yeah exactly let's put out the fire first and then let's rebuild so i think that you know these things are all going to be appropriate at an appropriate time and just as you indicated with diabetes let's understand why the person is having diabetes you you can really break 21st century medicine all the way down to one word which is why so we want to know you and i learned in medical school what what is it is it alzheimer's you know is it parkinson's you know we were very good at learning especially as neurologists you know once you name the disease that was it that's it because you're probably not going to do much about it now it's all about why it has shifted from what to why so what are all the things why did you get this disease same thing with diabetes and once you understand that there's a tremendous amount and this is one of the things that has concerned me the most we've all been told don't bother to go in early because there's nothing to be done if it's alzheimer's nothing could be further from the truth the armamentarium in cognitive decline prevention and reversal is huge and learning to use it appropriately the best things when yes there you know when do you want to use a cholinesterase inhibitor well after you've done everything else if you've now it may be that you're now doing just fine with your acetylcholine it may be that your diet was too low in choline as so many of us are and so it may be that doing the right things will get you back but if not fine you've now got that ability pharmaceutically to top that off but remember as soon as you're doing that something that is not natural that is not physiological you've got potential side effects some people are going to have some gut issues or some cramps with it i mean the key thing is the people who suddenly cold turkey it could potentially get worse with their cognition because as you know your body now responds by making more cholinesterase exactly what you don't want it to do and so if you suddenly cold turkey you could be in a worse position than when you started so please use the drugs at the appropriate time and the appropriate ways in your protocol um you you do emphasize as you know an important leg supportive leg the gut and detoxing the gut and supporting the microbiome and you know for all the downstream benefits they're from and it just seems you know not for me but i think for many involved in neurosciences attention to the gut would be about the last thing that they would consider yeah that's such a good point and you know uh we of course we hear more and more about how important the gut is in parkinson's is in alzheimer's you've written an entire book about the gut and brain and how they interact so these are all critical pieces and there's no question especially through the vegas for example but also through other all sorts of metabolic pathways there's a tremendous instrumentation here this really is a coordinated unit um this really does come back to systems biology and the the gut affects everything from your ongoing inflammatory status to how well you are folding or misfolding proteins in your brain to whether you are seeding with amyloids to you know what to uh production of specific neurotransmitters as you've pointed out before so this is such a huge connection and in fact many many of us have damaged guts have dysbiosis and these things are all critical to address if you're going to get best outcomes from cognitive decline you know there's so much in the literature these days that it's making it clear even from the the physicality of the connection of the vagus nerve as it relates to alpha synuclein making its way uh from the gut to the brain and the parkinson's patients speaking of parkinson's uh i i think you know it seems pretty clear that the numbers there percentage-wise are are are uh incredibly uh increasing and uh you know one wonders why but i think when we recognize the the much more uh obvious relationship of toxic exposure to parkinson's and you know the degree of toxicity of our world uh i i think it makes sense uh you know i was very taken a couple years ago to learn that there's this chemical manneb and mancozeb that are used to create parkinson's in the laboratory animal to damage cellular function to damage the mitochondrial function in certain human derived cells and that this chemical which obviously is locked up you can only get it for deep re research availability is available on amazon to kill bugs in your garden of your vegetable garden yeah i i i wanted to be sure when i spoke with you today that that was still the case and i looked it up last night and there it was it's it's truly um breathtaking that uh you know everything in the world of toxicology as in terms of what we are exposed to is innocent until proven guilty including for that matter glyphosate despite the fact that these you know the relationships to cancer are i don't say proven but uh certainly correlated in the court of law but still it you go to the hardware store and there are stacks and stacks of it no disclaimer and it's just as usual it's so uh you know that's where it starts why would you and i be having a discussion about that here we are talking about alzheimer's let me uh in the time we have left uh and this may run counter to your your you know razdan detroit but that is cultivating specific programs for the unique needs of the individual we've talked about as important as the day is long however could you for our viewers give us a couple of really good bullet points that if they're they're not going to the doctor's office and having a homo ir or uh blood sugar testing or monitoring or continuous glucose model whatever it might be just what are some of the broad stroke good things that we can be doing uh to keep our brains healthy yes and let me quick quickly comment on your point about parkinson's absolutely huge increases probably toxin-related you know trichloroethylene things like that anonymous another exposure that some people have that increases parkinson's and when we look at these different subtypes of alzheimer's what we found is that the toxic subtype of alzheimer's is actually more similar to lewy body disease and parkinson's so it's part of that group not so much the metabolic type of alzheimer's so but come back to your point about you know what can we all do absolutely and the number the number one thing we can all do is become metabolically flexible so number one thing is have a eat a diet just as you've pointed out over the years then we would say a plant rich this would be a plant-rich high fiber uh mildly ketogenic diet let me just stop here and say because aida always reminds me this is not atkins that's not what we're saying we're talking about a plant rich whether you want to be a vegan or just have a largely plant-related diet that seems to do the best with all the data for cognition high fiber high phytonutrient a diet with a appropriate fasting of 12 to 16 hours between finishing your dinner and starting your breakfast and you want to have no gluten no simple carbs and and preferably no dairy those are the big three that can give you a problem and of course again you've written a whole book about about these things and especially uh focusing on gluten it's a huge issue because of what because of its impact especially on leaky gut so that's the beginning of this and then uh you know people keep saying well wait a minute what's the drug i take and stuff so the diet turns out to be much more important than we were taught in medical school getting appropriate exercise and checking again i would recommend please check these simple things you can check you know check with an apple watch uh you can check your nocturnal oxygenation status you can check your heart rate variability see where you stand with stress so diet exercise sleep stress and brain training detoxification basics and appropriate supplementation simple things like whole coffee fruit extract which you actually taught me about a few years ago so i thank you for that very interesting and increases bdnf uh and it's turned out to be a very interesting supplement which many people use very successfully other things you know magnesium 3 and 8 making sure your vitamin d level is appropriate these are the basics that get most people on the right side of that equation so um though i think those are the those that's the way to start and i think that the toughest one there is the detoxification but there are some basics we can all do just as you indicated and that has to do with filtered water and it has to do with high fiber diets which turn out to be very helpful for detoxification and for improving your lip serum lipids and for improving your glycemic loads from the foods you're eating i mean by the way i'm going through this myself right now where i was eating too high carbs too low on choline it was clear i was hurting myself so i'm now switching over to more of a plant-rich uh you know mildly ketogenic diet with high phytonutrients etcetera um choline and so yeah so good point so i'm combining some pastured eggs with some acetylcholine that i've been taking and with some alpha gpc and then i check on chronometer so i'm getting around 550 milligrams per day which is the the goal for most of us now i have to say um i haven't started eating the liver yet um that's that's the next phase it can't happen on this side of the microphone whatever you could tell me that it you know it's going to win the lottery for me i can't do it it just can't it may be good for me but yeah we're getting all our easy probably good for all of us but i'm not there i'm not there yet either so those are the things that i've been doing but i do think you know the reality is we have to have a process that is essentially a hierarchical process the vast majority of us can simply avoid this disease by doing the right things starting at the age of 40 45 or so um and preferably even a little younger then those few who fall through the cracks okay you have more of an evaluation you get more push now the few that fall through those cracks you keep going until you get to the point where there will be a couple of people who will actually have to be in patience to have everything to see to see why they actually develop this when the vast majority of us can avoid it fairly easily if we start early on well you know i i had an interesting chat a couple days ago with cara fitzgerald who recently published a wonderful paper about a three and a half year reversal of the horvath dna methylation clock via an interventional lifestyle uh program which was not it was a unique specific program but not uniquely personalized and the point i'm making though is that she was went very light on the supplementation preferring uh to use food quality food and i think you know unless uh people are significantly d deficient whatever they may be in your program it sounds like uh you know you're really leaning on the food part of the equation aggressively and that that seems to be the you know the way the nutrients are packaged and uh therefore it seems like a good approach i had a nice chat with dean and aisha sharzai recently and though as you and i may differ slightly as and we may differ from the shares as who are full-on vegetarian um i think our goals are the same our goals are geared at good levels of nutrition fiber antioxidant function inflammation reduction and importantly keeping a blood sugar in check so i think we're all trying to get to the same place with subtle nuances of our approaches as of late i've modified my dietary recommendations as it relates to certainly organ meats and higher sources of purines like sardines and scallops and uh certainly as well not that's anything new keeping people off of fructose or recommending that in what i write because of their ultimate metabolism down to uric acid because we're learning so much now about the the pivotal role of uric acid sort of as an uh orchestrator of uh insulin resistance inflammation uh non-alcoholic fatty liver disease etc so you know every year we're learning more every every year that goes by and uh i always you talk about engaging your mind i think one of the best things a person can do though it's not widely available to engage their mind is to have a one hour conversation with dale bredesen that'll light you up well and i would say the same for you and by the way i i was one of the reviewers for kara's paper so and when i reviewed it several months ago said this is an important paper because this is really showing us that you can essentially age backwards uh changing your methylone changing markers that are biomarkers of aging so actually in our upcoming trial that we're going to do we will include those same biomarkers of aging so that we can see because my suspicion is we will see people actually aging backwards doing the appropriate things and i could you know i agree with you with the shares i think what they're doing is fantastic and the point is this is about neurochemistry that supports synaptic production and maintenance so getting those synapses to be forming be getting on the right side of that synaptoblastic synaptoplastic equation there are multiple ways to get there and being a vegan is a fine way to get there and including some fish and other things is a different way to get there but you can get to the same optimal neurochemistry well great to talk to you um you know it's great to know that you are continuing to push and and getting the results that you're getting and i think you know it's up to many others to make sure that the world knows the amazing things that you are accomplishing thank you so much david i hope we see you out here in california this summer and i hope that you and lee's are doing well as always fantastic to talk to you and yeah hear your wisdom thank you we'll love to aid it as well and we are we're going to make it out there you'll see all right fantastic we look forward we'll talk soon all right thank you david well i'm sure with you i am uh really amazed at what i'm hearing from dr bredesen what an incredible individual what a pioneer especially as it relates just not to his treatment of alzheimer's via his protocol but the whole notion of personalized medicine in other words trying to fit a treatment protocol to a patient's specific needs that certainly challenges the mainstream approach doesn't it but look at the success he's having what a show thank you for joining me i'm dr david prometer and i will certainly be back soon bye for now [Music] you

Channel: DavidPerlmutterMD

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Keywords: david perlmutter, dr. david perlmutter, grain brain, dr. perlmutter, brain maker, dcotor, medical, brain, alzheimers, heal, overcome, prevent, reverse, medical advice, doctor explains, heal the brain, brain health, memory, improve, diet, exercise, nutrition

Id: r1dXGLyu1gM

Length: 71min 57sec (4317 seconds)

Published: Mon Aug 09 2021