 Okay hello everyone we are live just checking looks like we're on and I am so excited about my guest today we met maybe five six years ago and just love I'm so excited to introduce his new book and the work that Dr. Dale Bredesen is doing just to really change the landscape of Alzheimer's and dementia so super excited to introduce him and before I introduce him just the little housekeeping bit you can find any information on blogs things I've written at JillKarnian.com we're now live on both YouTube and iTunes and anywhere you find podcasts so you can hear this on all of those and listen at your leisure and it'll be posted in the next several days there like I said lots and lots of other interviews that are available and lots of free blogs and writings there so let me introduce my guest Dr. Dale Bredesen. Dr. Dale Bredesen is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer's and the author of a New York Times best-selling book The End of Alzheimer's from Avery in 2017. He's also the end of Alzheimer's program in 2020 authored that book and he has held faculty positions at UC San Francisco UCLA and the University of California San Diego and directed the program on aging at the Burnham Institute before coming to the Buck Institute for Research on Aging in 1998 as its founding president and CEO he's currently a professor at UCLA and I think that's where I met you at the Buck Institute with one of your first events probably like I said five or six years ago just fascinating at how your research I remember the Inhalation Alzheimer's article what was the title that was the one that all of us in functional medicine first what was the title that published article that you would yeah inhalational Alzheimer's disease and an unrecognized and treatable epidemic and the idea was just basically what you've been seeing that so many people actually have cognitive effects from being exposed to mycotoxins and and you know we're seeing so many people who really have Alzheimer's by all the criteria pet scans spinal fluid etc and they're you know of the many contributors often the dominant one is mycotoxins yeah so and again that's my world and I see the same thing I don't consider myself an expert in Alzheimer's but based on your research I've certainly learned a lot and I remember something you said and correct me if this has changed but at one point in some of your research groups which we'll talk about today some of your patients you you said that especially the younger patients presenting with Alzheimer's there was about one in three that had some mycotoxin exposure that still somewhat hold true yeah if anything it may have gone up some what we're seeing and you know when I was training way back way back in the 80s we never saw people who were in their 40s and 50s with Alzheimer's disease this was late 60s 70s 80s but it's actually been shown the epidemiology has shown that there is much more young Alzheimer's these days that has been increased and when we look at those people they're often late 40s early 50s often around the time of menopause as you know or andropause and these are people who often present differently they often have some degree of depression they often have a non-amnestic presentation not always but that's a common thing and they you know they have executive problems they often will lose their jobs because they can't plan anymore they can't execute anymore they'll often have some dyscalculia they'll they sometimes have a posterior cerebral atrophy so called PCA or a PPA primary progressive aphasia you know word finding issues so there it's more of a bipyriatal than it is the classical by temporal where you lose memory and so often a different presentation and these people usually turn out to have some form of toxicity and the most common one as you know is mycotoxicity so and I think this you know this really hadn't been recognized by the Alzheimer's community so I think it's important for all of us to keep that in mind is as you know better than ever to anyone you're a real world expert in this area. Thank you Dr. Bresen and and I just have the greatest respect for the work you're doing because it really is giving us solutions to something that we thought previously was kind of unsolvable that we just you know assume these people have to put their affairs in order and we don't see that as much anymore especially when we catch it early my I love seeing these people who are younger with toxic load because I feel like I can make the most change in them let's go back I want to talk about your first work and just give a groundwork for the holes in the roof and the theory of Alzheimer's but before I do I want to hear your story of how did you get to be interested in this area of study and how did what was your journey to get to the Buck Institute tell us just a little about how you yeah thanks so I was very interested in neurodegenerative disease I was a postdoctoral fellow in Stan Prusner's lab before he won the Nobel Prize in 1997 and so I wanted to set up my own lab to understand what actually drives the neurodegenerative process we wanted to understand the molecular details you know why is it that it's very common why is it that it's completely untreatable as you know the area of neurodegenerative disease has been the area of greatest biomedical therapeutic failure whether you have frontotemporal dementia or Lewy body or Alzheimer's or ALS we just tell you we're very sorry and so we wanted to understand why that is and we spent years doing this and actually went to the to the buck from San Diego because at the time they were just going to open this new research institute that was on aging and I had this wonderful opportunity to be the founding president CEO so I thought okay let's let's begin to understand this underlying process and the surprise was when we looked at it it's quite different than the usual claim about Alzheimer's which is that it's some sort of misfolded protein and you and the problem in the brain is that your proteins aren't folding correctly well sure as part of a much larger problem but what we found is that this is really and if you go to the heart of what Alzheimer's is it is an insufficiency and so you've got on the positive side you've got the synaptoblastic things that are supporting you as you know things like your hormones and your trophic factors and your nutrients and your energetics your mitochondrial function blood flow oxygenation and on the negative side you've got the things that are the demands and those are things like anything pathogens toxins anything that is creating more demand on the system and when we're young we balance those pretty nicely but unfortunately for many of us and this dwarfs the COVID-19 pandemic unfortunately as you know we're looking at over 600 000 who've been killed by COVID-19 but about 45 million of the currently living Americans are destined to die of Alzheimer's if we don't find something that's really helpful so it's a huge pandemic and so when you look at that you see this balance and you see that okay everybody with Alzheimer's is on the wrong side of that balance and you can literally trace the molecular pathway the amyloid precursor protein itself sits in your neuronal membranes and when things are bad it is essentially protecting it goes into a protective downsizing mode it's interesting because it's an analogy to what's happened to our country with COVID-19 we were all told about a year and a half ago to shelter in place and social distance and of course the country went into a recession a protective downsizing mode your brain does that same thing through APP processing when you have supply that's not meeting the demand and so you involute so we realize okay this is a very different model we need to then instead of just trying to get rid of amyloid we need to look for each person as we started going through and there are you know we initially identified 36 different contributors the good news it's not thousands but it's dozens and so we said okay to the patients imagine you have a roof with 36 holes in it you've got to close a drug is an excellent way to patch one hole but you've got to do the other ones and I think in the long run you know drugs and and these precision medicine protocols functional medicine protocols are going to work together to do this but the surprise was just what you're studying the surprise was as we looked at these people we saw that there was a whole group where mycotoxins were the critical players in this downsizing event and which was really surprising because it hadn't really been in the literature and so as you said you when you see these people you really have to get on and treat their mycotoxicity and of course often they also have things like insulin resistance or sleep apnea or changes in their oral microbiome or gut microbiome leaky gut and on and on and on and so you know unlike this idea you just write a prescription for one thing and you're going to cover all 36 holes with one little hunk of paper that just doesn't work you really have to take a more functional medicine approach just as you do yeah gosh I love that because I love that I was trained as a medical doctor in allopathic MD we got great training just like you and we have this wonderful toolboxes I think drugs are absolutely appropriate but what happens is with this personalized approach the more functional medicine approach we're going to root cause and we've got a bigger toolbox so the exciting thing is now we have things that we didn't have before like some of the nutritional stuff I wasn't trained in medical school I had to learn post-gradually what does zinc do in these pathways and what does magnesium do and and then even the hormonal stuff it's interesting we learned it all in second year and then we have to kind of go back and relearn those metabolic pathways in depth because they actually really matter I love that you you touched on amyloid plaques and some of the anti-amyloid drugs do you want to talk just a little bit about that because like you said I want people to understand how that's actually protective and we start to attack we saw these drugs didn't really work like we thought do you want to talk a little about amyloid and and what the purpose is absolutely and that's the big you know one of the big surprises this was supposed to be the villain that was causing the disease but it turns out it's a response to multiple different pathogens it turns out to be an antimicrobial peptide for example so in fact you've got this your your body is making this because you've got these various insults and the pathologists have already shown us you look in the brains of patients with Alzheimer's you see p. gingivalis from poor dentition you see herpes simplex from the lip you see molds from things like chronic sinusitis you see spirochetes so on and on this stuff is making this to cover this again so you've got to kind of think in different way instead of just getting rid of the amyloid which is what these drugs do that you have to look at what's causing the amyloid and address those things so as you indicated back on June 7th the FDA took a very unusual step they approved a drug adu-helm which is aducanumab that all of their 11 out of 11 of their experts on their panel said should not be approved 10 of them strongly recommended against it one of them said i don't know nobody said this should be approved and you know they thought well look if you want to approve it do another trial because one trial failed completely one trial had a minimal benefit where it didn't make you better but it actually made things go downhill slightly less quickly 22 percent but at the risk of 17 percent of the people developed micro hemorrhages within the brain 40 percent of the developed brains swelling so some people have described this as the gaff that keeps on giving because it was an unusual unusual decision and in fact three of the people from the board then resigned in protest and of course now there's actually a congressional inquest into what the heck happened why was this approved and not only does it not help you much not only does it have side effects it costs about a hundred thousand dollars per year fifty six thousand dollars for the drug i know i mean it's really bizarre and then of course more for the infusions and all the scans you have to get so you're looking at about a hundred thousand dollars per year and again taking a functional medicine approach far far more effective far far cheaper uh and and so really getting much much better outcomes yeah and so this is so important because again we're if we had drugs that actually worked there's nothing wrong with that but what we're seeing is they're not addressing the root cause at this moment and again as we look even your research i think is driving the the better thought process around what might actually help do you want to just frame your first book talked about the different classes for people who aren't familiar with that first of all the name of your first book repeat that for our listeners so they can and where can they find your books because i think this is really important right so the first book was called the end of Alzheimer's and and to be to be fair that was a name that came from Random House not from me i get it my name for the book was wit's end which actually was suggested by my wife because that's both the research and the disease and i thought that was a wonderful idea Random House said nobody will ever buy a book called wit's end so we're going to call it the end of Alzheimer's we've gotten a little push back on that but the the point was simply to say okay for the first time we're beginning to understand what this process is and it was about the science and about here are some people who've actually gotten better and recently we finally got to the point of actually doing a clinical trial which was now posted on med archive then after the first book everybody said hey we want more details and so we then the second book was about details and then the third book just came out is all about the survivors talking about their stories and what they went through and as you indicated one of the parts of the first book was to say well look when you start to look at all these different all these different players you're looking at inflammation and you're looking at the microbiome and all these things what you find is Alzheimer's is not one disease it's really six different subtypes so there are people who are more on the inflammatory side as you know there are people who are more on the atrophic side and then there's an interesting mix of those people who are glycotoxic who have the insulin resistance that gives them the type two the atrophic but they also have the glycotoxicity so they have non-enzymatic glycation of hundreds of proteins which we measure as hemoglobin a1c of course but there are many others affected and so they've got the worst of both worlds very common problem and then that's type 1.5 then type three is tox toxins and those as you know three different ones the inorganics including for all of us who've been in the western fires we are at increased risk no question air pollution increases your risk and then the organics things like glyphosate and toluene and benzene and things like that and then of course the biotoxins things like trichothesenes and all the things that you're dealing with on a daily basis so that's type three then type four is vascular type five is traumatic so these are you know different people have different presentations and of course as you said you have to get to the root cause for each person you have to have a personalized precision medicine type of approach to get the best outcomes and you know we're seeing better and better outcomes in the trial that we just completed and I was really honored to work with Dr. Anne Hathaway, Dr. Cattup's and Dr. Deborah Gordon they were just fantastic and of course they sing your praises as well and they did a great job and 84% of the people improved didn't just slow their decline but actually improve their scores and the most exciting part is we now have people who are over nine years with sustained improvement which was unheard of before so we're very excited and nevertheless of course there are a few people who don't and we'd like to understand why what is being missed are they too far along if they are far along are there things that we need to be adding what is missing so that we can help every single person the good news since if you start early just about everybody gets better so reality is Alzheimer's is becoming an option nobody really has to get this if you simply get on prevention or early reversal you have quite a window SCI itself subjective cognitive impairment lasts on average 10 years and that's a very early stage the big concern as you know there's something called mild cognitive impairment and as one of the seven survivors wrote Frank he said when his doctor first told him he had MCI he said there's nothing mild about this right and that's the problem it's the third of four stages it's not the pre-symptomatic it's not the SCI but it's the third stage out of four it's a little bit like telling someone oh don't worry you've got mildly metastatic cancer this is a relatively late stage and so you absolutely want to get into everything possible but preferably you know preferably you never get to that stage so I love this Dr. Breslin because again I tend to I don't my patient population isn't just like a brain clinic or an Alzheimer's but what I see is people in their 20s and 30s and 40s young young people and so if you're listening and you're starting to have cognitive impairment of any type this is not normal and so find a doc who can help you find root cause because literally if we if we would get awareness of people in their 20s and 30s and 40s we could probably make even a bigger change because that's where you have complete plasticity to make a difference and to see your toxic load and to see your metabolic status before you actually always think of health as a trajectory we're either walking towards disease or away from it and so if you're proactive as a younger person you can actually change this you can find your APOE4 status if you have that or not because that's going to make you at higher risk meaning you need to start earlier for prevention now I wouldn't have mentioned your type 3's which is that toxic again that's a primarily part of my practice I had just an incident just three of those things in my personal brain health recently we had the fires and if you look I've got an article coming out this week on all the toxic metals chemicals benzene things that are in this fire smoke we're seeing Dr. Akerli and I just talked TGF beta which is an inflammatory marker in the blood will go up just from the smoke from the fires so some of these things are actually affecting markers in the blood and I had that instance with my breathing and then I got my car was in a little accident fender bender minor thing but it had to be painted I got it back from the auto body shop and for two days I literally was narcoleptic I get out of that car after 30 minutes the BOC's from that toxic auto body paint the benzene's and those chemicals they put me comatose for almost two days I thought it was worse than a mold exposure and so people who are in that industry again if you're not aware those things are so toxic to the brain and then I pulled up the studies and there are lawsuits out for people who've been in paint and body shops for auto body types of things because it's so toxic the benzene's and stuff so we had the smoke from the fires for me and I had all these experiences and then recently I had a friend who had ketomium in the house and I had an exposure there and same thing it just like for a whole 24 hours and I could not think I could not function so this is very real I'm in my 40s and so and again I have real good cognitive I don't feel like I have impairment but even so just those exposures in it in one day take me out it makes it really difficult to process so we need to be thinking about how we can have a good air quality and how we can actually prevent because like you said you're getting these people and you're making reversal when they're diagnosed and then people like me my job is to find the pre-clinical states and how do we keep people from ever walking towards that disease and we should that's the thing this disease should be a very rare disease it's because people don't realize that and we're all told there's nothing you can do and they wait too long and you brought up a critical issue which is brain fog this is something that affects so many people and of course with COVID-19 it's becoming even more important there's a big concern that in the future we'll have a huge increase in Alzheimer's disease because of all these people who've gotten COVID-19 and have had some brain fog gotten better but now are at risk for decline because there's no question this virus does affect the brain it does affect the vessels within the brain for example it's got the neuro inflammation as part of it so it really does by multiple mechanisms increase your risk and as you know there have already been a few patients with Parkinson's that came on literally with the COVID-19 so there is a concern that there will be you know a neurotropic related effects of this virus down the road and therefore anybody we always recommend anyone who's had this please get on prevention please get what we call a cognoscopy yes you know everyone knows you should get a colonoscopy when you turn 50 and we'll recommend for everyone who's 45 or over please get a cognoscopy it's actually much more pleasant than a colonoscopy and you can find out where you stand and see it just the sort of things you were just talking about if you have you got exposure to these various things because they will indeed increase your risk so love this and I want to talk about because you're training doctors and so I have a limited practice and you you know but there are doctors out there and the ones you mentioned that you're doing research with there's some good friends of both of ours that are doing this how do people find your work and the doctors who have been trained with the recode in that tell us just a little about for those people listening how do they find a good doctor that does what you have been teaching yeah that's a great point so you can just go on drbredesen.com or you can go on apollohealthco.com we're working with Apollo Health because we believe that the future of medicine is in larger data sets it's so interesting to me you know Google knows where you shop Google knows a lot about your life and so they're you know they're gathering all these data and yet why is it that we as physicians aren't gathering in these incredibly complicated people that we're dealing with human organisms we should be looking at much much larger data sets but of course the way you and I were trained and especially way back in the caveman hero when I was training is I'm much older but back then you know people would basically say what's the disease make a diagnosis write a prescription or send them to surgery and there was no asking why there was no understanding physiological changes if someone had hypertension you wrote a prescription for anti-hypertensives instead of asking why did they get hypertension so I think this is you know this is part of 21st century medicine. Love it and what I'm finding I mean years ago I was the outcast in medical school who did you know integrative club that I brought in different modalities and exposure at Loyola I was and I was one of the first that was kind of really talking about it in med school but what's interesting now is people thought I was a little crazy back then and now my colleagues they call me all the time and say Jill I have this problem I can't solve do you have any because they see that all of us see we went into medicine wanting to heal people right and if our heart is in that healer space when we encounter things that we don't have answers to we say why we say is there anything else so that's why you and I and all of our colleagues that are doing this are open to other things and my thing is always risk benefit analysis if there's like something like adding extra vitamin C or checking hormone status and the risk is very low with an intervention even if I don't know for sure that there's a very large randomized controlled trial out there to prove it I will often try things that I feel like are incredibly safe because the risk is very low and that's how I usually determine you know what kinds of things and then we have people like you who are putting out the research to support the things that we're doing as intervention and to continue putting out good research on the things that we can do because we have a lot of control we're led to believe that we don't and if you're listening and you think it's hopeless it's not there's a lot of hope out there so that's where people can find and then what tell us about this new book and it sounds like patient stories tell us about more about that well you know in the very first person we call patient zero started back in April of 2012 I mean all I had to offer was a person had told her she lived on the east coast you know come out to the west coast there's some sort of research going on out here you know I hadn't seen a patient in 20 years just we were looking at mount timers and alts climbers and cells dying and things like that yeah and so she asked me if I would see this person I said well look I you know I don't see patients but I'm happy to talk to her we spent several hours going through the whole idea and what this is and she took this back to her doctor and then she called me about three months later and said I cannot believe it my memory is better than it's been in 20 years you know this theory seems to be working so I was really excited at the time I thought wow you know we've been doing this and we've been turned down for a clinical trial back in 2011 so we then started you know started getting more and more people and the as you know the best thing of all after all of the discussion about the models after all the discussion about the various approaches to this the best thing of all is to hear from someone that they're better to hear how it's changed their lives and people would say you know my children are so happy and Julie's story she mentions that you know her son was crying when she first told him I've got Alzheimer's she was apoE44 so she's at the highest risk group she's already having significant problems she went to a neurologist and she said could you at least keep me where I am and he said good luck with that which was very unfortunate because he just felt there's nothing we can do so you know her son was crying she got better and so she just recently went to her son's wedding so these are the best stories hearing of how people have done better as you said we all went into medicine we all want the same thing we want to see people get better and this has been an area where people don't get better and so one of the things we're trying to do now is can we adapt the chemistry of this for all of these other diseases and we're so we have a few the initial people with macular degeneration that has its own chemistry and can we now adapt this for Lewy body and for various other things although to be fair the Lewy body people are very much like type 3 they're the toxic ones as well and they respond pretty well so that was the idea I thought okay I'd love to have a number of the people who've gone through this and done well and written these wonderful emails or phone calls I'd love to have them write their stories about how did it impact their families Deborah is another one just amazing she's a brilliant attorney who went to Harvard she lives back east and she wrote about how her father a brilliant neurologist died of Alzheimer's her father's mother also died of Alzheimer's when she was getting the first symptoms she knew it because she had seen what her father went through she looked at her children and realized oh my gosh you know what's next and so she then ended up going she was actually evaluated at a major medical school and they showed that she had actually improved and said to her like what are you doing here how come you're better and she's you know she's done very well she wrote a beautiful story about what this meant to her and to her family and so I thought not only is it wonderful for people to see these heartfelt stories and to get inspiration to say hey I can do this too we really can reduce the global burden of dementia but also they talk about what worked best for them what are the things that actually helped them the most what are the things that helped them the least so it really gives you some pointers as well as some inspiration oh gosh I love that and and it's a team approach because if you have someone with subjective or moderate or mild cognitive decline you really need some you know the family members and the caretakers and everybody involved so sounds like you're telling that story as well so I know we have a lot of physicians who listen to us too Dr. Bresen and if they're listening and they're like I want to learn this protocol tell us more about where where do you offer training is it where would you recommend that a doc who wants to know more about how to treat patients go for more education yeah and we just set up a new RICO 2.0 several months ago I mean there are now over 2,000 people who've gone through the training physicians from 10 different countries and all over the USA as you know and so they can go you can see this again you can go to drbredesen.com or you can go to ApolloHealthCo.com and they and the training is offered there it's online so it's available I love that because we really need to reach more and more and so we'll be including those links wherever you're listening to this we will include those links so you can check that out as well so I don't want to go too deep because we go really deep with what do you do for diagnosis but just an overview there is a big panel of labs that you recommend and that I draw on these patients we don't have to go through all of them but let's talk maybe about just classes like hormones and minerals and then also the cognitive scope what would you involve in a person who's just wanting a diagnosis what basic things would you involve for that if they wanted to ask their doctor for those tests it's a great point because as you know you don't really need to do as much for someone who's just there for prevention assuming that they're doing well on their testing so when we talk about a cognitive we include as part of that a simple online cognitive assessment because as you know this can sneak up on people we've had people come in for prevention and it turns out they have fairly significant mci we had one woman who we had a mocha of 23 and actually she was treated went up to mocha third perfect score of 30 stewin very very well so as you indicated what we want to do is we want to look at the very things that are the root causes so we need to understand something about the inflammatory side and then all the different subtypes that I mentioned so we'd like to look at things like hscrp and tgf beta one but we'd also like to know what's driving this so do you have you know poor oral microbiome and so we do look at an oral microbiome for people we want to know what your gut status is and this was all included by the way in the trial that we did with with an and cat and debra and we want to know then the basic markers for inflammation we want to know your homo ir so we want to know your metabolic status as you know this is such a common contributor even if it's not the only contributor it's a common contributor and there are about 80 million americans or so with insulin resistance so this is a common problem and this is as you know this is a problem for your brain we used to grow brain cells when we were in the lab we grow brain cells in a dish and you always had to include insulin in the medium or else they would die so it is a very important growth factor for your brain as our ngf bdnf these other things that we're trying to improve so we'd like to know where you stand with your glyco toxicity and then we'd like to know where you stand with your various hormones and your various nutrients and as you know many of the same risk factors for poor outcomes for a covid 19 are the same ones for Alzheimer's so low vitamin d now hypertension obesity insulin resistance vascular disease these are all for both metabolic syndrome all of these things are important in both of these so we'd like to look at all those and that includes things like your thyroid status and you know free t3 not just tsh but looking at more very much at an ifm sort of approach and then we'd like to know what your vascular status and that's as you know that's not always easy and more and more we're finding that that is a critical one the energetic part of this so it's the vascularity and then it's the oxygenation and we're looking at things like your nocturnal oxygenation what is your spo2 are you dropping that so many people are without realizing it and i do think that some of these wearables very helpful these days because people are now doing things like looking at their apple watch and saying oh my gosh you know i dropped to 85 percent oxygen saturation last night that's a concern is there's something going on here and that can absolutely be a contributor and of course mitochondrial function and interestingly some of these you know this is really evolving in real time and so as you know you know some of the issues that i'm sure you've dealt with and for example with people have suggested methylene blue as an example for something that may be helpful not clear yet not proven and is this something that you like to use or not oh so i love that you mentioned this because one of the things i see now i'm just going to take a side note really quick when my really good friends is the neurosurgeon for the Denver Broncos so what he sees is concussion and how concussion contributes to you know early onset to mention those kinds of things and even just cognitive decline in general and he said over and over the literature he's a conventional neurosurgeon although he knows functional medicine he's a jill there is no doubt the data supports that if you have a plain old concussion and you have no infection no toxic load no metabolic insufficiency and no inflammation you're probably going to be fine it's concussion plus which is exactly what we're talking about here so it's concussion plus oh in Lyme disease and infection i want to talk about that in just a second or toxicity like mold and mold and Lyme happen to filter to the top of our radar because they're so toxic it doesn't mean that other viruses like epstein bar or HSV or CMB or coxsac or other toxins like benzines don't contribute but we just happen to you and i see a lot of this mycotoxin and a lot of Lyme so methylene blue happens to be really effective against uh an infection called Bartonella and Bartonella particularly affects the brain and nervous system probably worse than anything else in fact just yesterday i had a consult with a 19 year old college student who had uncontrolled rage and out of control anxiety turns out Bartonella was the player and it was his mental status and it was really profound to see like how it affected his family and him and how when he described it was like it was out of proportion to what he knew himself to be if i can say that it was almost like the infection really contributed to his response his irritability his almost like the brain was overwhelmed or the brain was on fire we use those terms but and it's really relative whether it's a young person with infection or an older person with Alzheimer's it's brain on fire in different ways right so i think the methylene blue and some of these even antibiotic regimens or anti mold regimens are so critical because these are surprisingly inflammatory to the brain i think some of the worst brain imaging that i see is related to mold and Lyme it really does affect the brain very interesting because of course it also has the effect to bypass if you've got if you look at mitochondrial complexes complex one is typically abnormal in Parkinson's with Alzheimer's it's been complex four that's been associated so at least theoretically if you have an inhibitor of complex one you may actually be able to bypass that with methylene blue again that's theory and i think there's a lot that we don't know yet but so we want to look at all these different things and then we want to look at your mitochondrial function as i mentioned earlier and where do you stand with ketosis you need something you know you need to to get the blood there you need to get the oxygen there but you'd have to have a substrate to burn and of course most of these people who are developing cognitive decline are not metabolically flexible so they're not able to go back and forth between ketosis and and burning glucose and that's actually critical and so again getting them to optimize this is very very helpful let's talk about diet a little because that's one of the core components of what we do with intervention and what you've taught in all of your trainings all of this time i know you're a big fan of ketogenic diet and i completely agree well let's talk about real quickly like what for the layperson what why is that important and what are there some subtypes that may not do as well in ketogenic diet yeah this is a really good point and you know i like you did not train as a nutritionist yeah so i then when i went to medical school there was a single course on nutrition and it was optional and i took it and i just learned one thing which was on tpn the ivy after surgery right like a total perennial nutrition exactly so the fact of the matter is you know we're agnostic whatever helps the brain the most is what we want to use so what we've what we've looked at is something we call keto flex 12-3 and the it's a simple idea that we'd like to drive people into mild ketosis now why do we want to do that as you said when you look at a PET scan you can actually see for people who are apoE4 positive you can see often in their late 20s there are already decreases in glucose utilization in the temporal and parietal regions and that is the hallmark of all science the signature of Alzheimer's disease so you want to be able to bridge that gap and as dr steven canane has taught all of us over the years you can bridge that gap with increasing ketones so now you're able to burn not just glucose where you're not doing a perfect job now you add the ketones and you get into you know mild ketosis 1.0 to 4.0 millimolar beta hydroxybutyrate or so it helps you so when we see people with cognitive decline to me that is an energetic emergency we already know that things aren't going well in the temporal and parietal regions with glucose utilization so we want to do a couple things at once we want to start making them insulin sensitive we want to make them now metabolically flexible and we want to get them into some ketosis so that they bridge that gap and they often notice oh my gosh i'm sharper when i have the ketones on board now as you indicated there's a concern because people who are very thin can have trouble with this they don't have the fat to burn so we recommend okay at the beginning just do exogenous ketone do some mct oil or some coconut oil or some you know or some ketone ester or salt just to get it up there that's the quick fix over time you can drive yourself into endogenous ketosis which has some advantages over exogenous ketosis but because there is an energy emergency at the beginning please address that and it should help you because we worry again the people who are very thin they're trying to get themselves into ketosis now they have no glucose they have no ketones and they actually get worse so you have to be very very careful i love that you clarify because again so many people benefit but there's a small subset i find them more likely atrophic the older the ones that are deficient in some of the hormones because those hormones if you have low cortisol and low estrogen loads you often are less flexible with burning ketones as your fuel versus sugar so less and you try to go into fasting and it makes things work and then also the gut such a big player because if you have celiac or Crohn's or some of these things with the gut and you have malabsorption of fats then you can eat all the fats in the world and they go right through you and you're having trouble getting them to the sources to the cells that actually need them then one last category the ApoE-4-4 is i find that again i love your opinion on this but sometimes because you need a really high fat diet you definitely need to moderate the sources of fats because if you're doing really high saturated fats you're going to drive their issues with the ApoE-4 and the hyperlipidemia up a little any thoughts on those particular people the ApoE-4-4s and absolutely yes and we did some work for years on the molecular mechanisms of ApoE-4 and what we found very surprising ApoE-4 actually enters the nucleus interacts with 1700 different gene promoters and literally changes the programming of your cell toward a more pro inflammatory state so it is again protecting you and it's what presumably why it's the primordial it's what allowed us to come down on the off the trees and be walking around the savannah and you know stepping on dung and things like that so yes you're absolutely right with the four fours you want to make several adjustments number one be careful about their lipid status you want to look at their LDL particle number and you want to number two you want to give them more on the unsaturated fat so more toward the EVOOs and things like that and away from the coconut oil you want to be a little bit careful about that and they do tend to absorb it they are better absorbers than the ApoE-4 negatives and then the third thing is you want to remember that ApoE-4 itself is a pro inflammatory gene and it's interesting we're starting to see how all these things match up with the immune system so A beta itself is part of the innate immune system and just as people with COVID-19 die from cytokine storm people in Alzheimer's die from cytokine drizzle because you've got this smoldering long-term problem with these cytokines and A beta is essentially one it's part of that innate immune system ApoE-4 also we see very clearly is a pro inflammatory gene one of the things that it affects with these 1700 gene promoters it turns down some of the genes that normally limit the inflammatory response so now you have less of a turning down of your pro inflammatory response so that's where things like resolvance can be very useful oh that makes so much sense and like you said there is the protective benefit is they tend not to be more the toxic and infectious type as much so they're more this inflammatory and then the ApoE-3-3s are the ones we see with the type 3 toxic again that's a generalization but there's a little bit of a tendency in that direction so yeah so in our last few minutes what's on the horizon is there anything that's being studied or kind of new in this protocol or that you see being potentially something we'll look more towards in the future where are we headed with this research yeah this is a great point so we're now moving to a larger trial which we'll be starting and again with Anne and Kat and Deborah we'll be starting actually with probably also a few others because this is going to be a larger study so that should start next year second thing is to now as I mentioned earlier adapt this to other things can we now if we we understand the root cause just as you said what about if we look at macular degeneration louie body ALS I mean ALS has been one of the ones as a neurologist this is one of the ones that bothered me the most these people go downhill relatively rapidly it's a relatively common disease unfortunately and it's just horrible so we need to now look at the appropriate chemistry for that and go after that so we started something called the ARC the ARC trial so we're just looking at very small numbers of people with each of these different diseases to see if we study them very deeply if we do a deep dive you know can we see improvements and then the third thing is something called the SARA trial which is coming up and this is severe Alzheimer's reversal attempt so the question then is we all we'd love to get everybody at the SCI or early MCI stage and we had even some people into the Alzheimer's stage in this recent trial but what about the people who have mocha scores that are single digits and some of the interestingly as you know some of them really do get better they don't get all the way better they get somewhat better now sometimes it makes a huge difference they can dress themselves they can speak again but often they don't get better and I really want a quick shout out here to your friend Dr Heather Sanderson down in San Diego who's opened Marama which is the first assisted living facility I'm aware of that's doing the same sort of approach and seeing people improve in their assisted living facility but what do we do we'd love for people never to get to Alzheimer's but for those who are far along what are the things we have to add you've talked about intranasal trophic factors you've talked about some of the peptides you've used some beautiful approaches that you've taken stem cells another one and you've talked about this before as well I think all of these things have potential roles we need to again understand the chemistry well enough to know what are the critical pieces to take people who are fairly far along and bring them back as far as we can yeah oh I love that and this is just so encouraging like I said I'm excited because I want to share it with physicians but also patients listening and talk to your doctor get get them excited about what's potential out there because they can go to Dr Dale Bredesen's website and get more information and you might be the person if you're the patient asking them you might be the person that encourages them to get more training we need more doctors trained Dr Bredesen I can't thank you enough for your work I really you are up there in the top you know handful of doctors I have such great respect for so many you are up there in my book on what you've provided to the world the the depth of information you've added and the information that you've given to us as clinicians you know down in the trenches to help us with our practice so I publicly want to say thank you so much for the work you're doing I just love love following that and continue to support it thank you so much I really appreciate it and you are doing such great work and getting so many people better so thank you and as you mentioned earlier you're also seeing people younger and really preventing the problems of the future so thank you for the great work you're doing and I look forward to the day when all medical schools will teach modern medicine that would be fantastic yeah awesome well thank you so much Dr Bredesen um hopefully we'll probably do a part two of this at some point thank you Dr Jill it's so great to talk to you you too bye bye okay bye