Keys for Preventing Cognitive Decline

How to prioritize interventions for brain health with Dr. Dale Bredesen.

Single drug treatments for Alzheimer’s disease and dementia haven’t been successfully found, but Dr. Dale Bredesen’s 36 point plan has reversed cognitive decline for some patients. In today’s podcast, Dr. Bredesen shares how to prioritize key brain health markers to improve cognitive function and reduce risk factors for dementia and Alzheimer’s.

In This Episode

Dr. Bredesen’s Background … 00:04:36
Classifying / Subtyping of Alzheimer’s Risk … 00:09:46
The Oral/Gut/Brain Connection … 00:18:03
Insulin Resistance … 00:22:11
HOMA – IR … 00:25:24
How Diet Impacts Cognitive Function … 00:31:02
Atrophic and Vascular Type … 00:34:22
Accuracy of Self Monitoring Devices … 00:39:58
Head Trauma … 00:45:34
Episode Wrap Up … 00:51:49

 

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Hi everyone. Today I spoke with Dr. Dale Bredesen. This is part two on his multicomponent, about 36 component model, for prevention of cognitive, Alzheimer’s, dementia, and the like. The main reason behind having him back on was because his 36 component model is fantastic. I think it is bringing very important acknowledgment of treatable, underlying factors that lead to the travesty of cognitive decline. However, 36 components is a tremendous amount for clinicians to grapple with, or for a person on their own reading a book to execute. As I’ve harped on in the podcast many times before, and have also discussed in Healthy Gut, Healthy You, having a hierarchy and kind of an algorithm to prioritize can really help reduce the confusion, decrease the time to healing, reduce the lab burden and just generally lead to better outcomes.

That was what I really wanted to dig into in this episode. Dale did an excellent job. He has now broken down the model into subtypes. I find this incredibly helpful because now, instead of looking at 36 factors and trying to parse through them and likely struggling, we now have subtypes. One is inflammatory. Guess what comes up with inflammation? Oftentimes gut health. The other is vascular for those who are not doing anything that allows good blood flow to brain-like exercise, vascular may be an issue. Glycotoxic for those who have high blood sugar as another category. So we’ll go into the system or the subtypes in more detail in the podcast, but just wanted to kind of give you this, this kind of summary on what we will be discussing today. One or two other things I want to point you to. Type 1 in this subtype model is inflammatory. This encompasses gut, sinus, and periodontal or oral health.


Sponsored Resources

Let’s talk about one of my favorite tests for digestive health, the GI-MAP from Diagnostic Solutions, who has helped to make this podcast possible. Now if you’ve been reading any of the case studies that I’ve published in the Future of Functional Medicine Review clinical newsletter, you’ve likely seen that this test, the GI-MAP, is a test I frequently use in my practice.

Keys for Preventing Cognitive Decline - diagnostic solutions

Why? Well, one of my favorite things about this test is it has excellent insurance coverage. So this is a few hundred dollars that I save patients. This lab is also CLIA certified, which is essentially the quality assurance bureau for labs. So it’s important that these labs are being monitored, not cutting any corners. That’s where you get your CLIA certification.

Now, this test uses quantitative PCR technology. So it’s a DNA test. And you’ll get a good read on dysbiosis with this test because they will assess and report out various types of bacteria, yeast, and parasites including protozoa, worms, and amoeba. They also have some valuable and helpful clinical markers like calprotectin which can help rule in or out inflammatory bowel disease, and zonulin, a marker of leaky gut. So head over to DiagnosticSolutionsLab.com to learn more and to order your test.

A great resource for you is Healthy Gut, Healthy You as I mentioned quite frequently. I want to also remind people of the meta-analysis that has found that probiotics can help reduce periodontitis. There are some simple ways to reduce inflammation as perhaps one of the main underlying factors of cognitive decline. It’s not the only factor, but it’s definitely an important and treatable factor that can be remedied. So if you’re looking to make a dent in the inflammatory status of your own body, consider the action plan in Healthy Gut, Healthy You, and/or a good well-rounded probiotic protocol, which can really help reduce the gut-associated inflammation. Now we’ll go to the call with Dale, his mode is as follows: Type 1 – Inflammatory, Type 2 – Atrophic, Type 3 – Glycotoxic, Type 4 – Vascular, Type 5 – Traumatic (such as head trauma).

So if you’re looking to optimize your brain health, definitely in my experience, as you probably know, having had brain fog while my gut was in disarray, your gut health is a very important facet. Dale has now helped to bring other facets into a rubric of these subtypes, with the ability to identify where you may flag and some action items on what you can do. So we will now go to the call with Dale Bredesen.

➕ Full Podcast Transcript

Intro:

Welcome to Dr. Ruscio radio providing practical and science-based solutions to feeling your best. To stay up-to-date on the latest topics as well as all of our prior episodes, please make sure to subscribe in your podcast player. For weekly updates, DrRuscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking to your doctor. Now let’s head to the show.

DrMichaelRuscio:

Hi everyone. Today I spoke with Dr. Dale Bredesen. This is part two on his multicomponent, about 36 component model, for prevention of cognitive, Alzheimer’s, dementia, and the like. The main reason behind having him back on was because his 36 component model is fantastic. I think it is bringing very important acknowledgment of treatable, underlying factors that lead to the travesty of cognitive decline. However, 36 components is a tremendous amount for clinicians to grapple with, or for a person on their own reading a book to execute. As I’ve harped on in the podcast many times before, and have also discussed in Healthy Gut, Healthy You, having a hierarchy and kind of an algorithm to prioritize can really help reduce the confusion, decrease the time to healing, reduce the lab burden and just generally lead to better outcomes. That was what I really wanted to dig into in this episode. Dale did an excellent job. He has now broken down the model into subtypes. I find this incredibly helpful because now, instead of looking at 36 factors and trying to parse through them and likely struggling, we now have subtypes. One is inflammatory. Guess what comes up with inflammation? Oftentimes gut health. The other is vascular for those who are not doing anything that allows good blood flow to brain-like exercise, vascular may be an issue. Glycotoxic for those who have high blood sugar as another category. So we’ll go into the system or the subtypes in more detail in the podcast, but just wanted to kind of give you this, this kind of summary on what we will be discussing today. One or two other things I want to point you to. Type 1 in this subtype model is inflammatory. This encompasses gut, sinus, and periodontal or oral health.

DrMR:

A great resource for you is Healthy Gut, Healthy You as I mentioned quite frequently. I want to also remind people of the meta-analysis that has found that probiotics can help reduce periodontitis. There are some simple ways to reduce inflammation as perhaps one of the main underlying factors of cognitive decline. It’s not the only factor, but it’s definitely an important and treatable factor that can be remedied. So if you’re looking to make a dent in the inflammatory status of your own body, consider the action plan in Healthy Gut, Healthy You, and/or a good well-rounded probiotic protocol, which can really help reduce the gut-associated inflammation. Now we’ll go to the call with Dale, his mode is as follows: Type 1 – Inflammatory, Type 2 – Atrophic, Type 3 – Glycotoxic, Type 4 – Vascular, Type 5 – Traumatic (such as head trauma).

DrMR:

So if you’re looking to optimize your brain health, definitely in my experience, as you probably know, having had brain fog while my gut was in disarray, your gut health is a very important facet. Dale has now helped to bring other facets into a rubric of these subtypes, with the ability to identify where you may flag and some action items on what you can do. So we will now go to the call with Dale Bredesen.

Dr. Bredesen’s Background

DrMR:

Hey, everyone. Welcome back to another episode of Dr. Ruscio radio. This is Dr. Ruscio and I have back with us again, Dr. Dale Bredesen. We’re going to be following up on his model for, I guess you could say broadly, underneath the rubric of brain health. We are going to dig more into his 36-point model. How do we try to prioritize various aspects of that model for the individual? In keeping with this theme we’ve discussed on this podcast, there is a lot we can do for someone, but having a hierarchy can be very, very helpful in prioritizing and focusing on the things that need to be addressed that can make care less expensive and certainly get you, more quickly, to the goals oftentimes that you’re trying to reach.

DrMR:

So we’re really appreciative, Dale, for you coming back on the show and having a chance to try to get to the highest level of efficiency and application of your model that we can.

DrDaleBredesen:

Thanks so much, Michael great to be back.

DrMR:

In case people missed the first episode, can you give people just a real short synopsis of your background?

DrDB:

Absolutely. Yeah, so I’m a neurologist and a neuroscientist. I ran a lab for 30 years and the whole point of our laboratory was to understand the fundamental nature of the neurodegenerative process at a molecular species-level so that we could understand things like Alzheimer’s and Lewy body disease and ALS to begin to fashion the first effective treatments because this is the area of greatest biomedical therapeutic failure. Back in 2014, I published the first paper to show the reversal of cognitive decline in patients with Alzheimer’s and pre-Alzheimers. We actually published another hundred documented improvements in 2018, and then just published the second book on this a couple of weeks ago. Awesome.

DrMR:

Awesome. Fantastic area of study and I agree with you that neurological conditions, and I would also argue actually gastrointestinal-based conditions, are two areas where conventional medicine may fall relatively short. Certainly, that’s a very broad statement and that’s not going to be universally true. There are facets, I think in conventional medicine that do a great job for certain neurological and gastrointestinal disorders, but on the whole, knowing that so many of these are chronic and degenerative in nature, it just seems that the conventional model isn’t aptly suited for what is the driving factor or factors for many people. I know we line up on that. So we discussed last time you were on the 36 point model, and before we started the recording today, you said something that I think is just so important I wanted to reiterate it, which is, this is a newer and emerging field. As a field is developing, we become more, more efficient. Similar to the Robb Wolf analogy of a cell phone today can do way more in a smaller device than it could previously due to efficiency gains. So a natural part of the evolution of any facet of healthcare, hopefully, is becoming more discerning, more efficient. That’s why I’m so excited to discuss the model, because 36 components, that’s a tall order for a clinician to work with and also for patients. That being said as a quick aside, one of the really endemic problems I see in integrative and functional medicine is that it is kind of like the paradox of plenty. We have plenty of options, but the paradox is that some providers feel they have to execute all of those options. This is where we’ll see the horror stories of $6,000 worth of lab testing or a $20 – $30,000 care package recommended. It is also why I think those are probably predominantly done with benevolent intentions. You know, it’s not the optimal due to the cost and the invasiveness and in the number of pills someone has to pop. That’s why I’m so appreciative of the conversation we’re jumping into today, which is how do we make this more manageable.

DrDB:

Is it a great point. It gets back to the point that if you’re trying to develop a single drug and you’ve got all these different things that are all contributing to your cognitive decline, typically we find that people have between 10 and 25 different contributors to cognitive decline. So we have to prioritize them. That is a very tall order for a single drug. I think that’s one of the main reasons why all of the drugs have failed. Even the ones that have “succeeded” have had absolutely minimal impact and really don’t change the trajectory downward in these cognitive decline related diseases, such as Alzheimer’s. So you’re absolutely right. We went from bench research, we simply said here is the pathway that is critical. There are many things that play into this pathway. Originally, we identified 36, there are now actually a couple more. What we need to focus on is the top priority items.

Classifying / Subtyping of Alzheimer’s Risk

DrDB:

So what we did was to classify these and we published several years ago, the subtyping of Alzheimer’s and Alzheimer’s risk. You can see very clearly that some people have what we call Type 1 or inflammatory Alzheimer’s. So in those people, it is critical to ratchet down that inflammation. Then, of course, to determine, most importantly, what’s causing the inflammation. Is this leaky gut? Is this periodontitis? Is this chronic sinusitis? Is this metabolic syndrome? Then Type 2, which is atrophic, is a very different cause of the disease. These are people that don’t have a lot of inflammation, but what they do have is reduced support, nerve growth factor, brain-derived neurotrophic factor, estradiol, testosterone, vitamin D progesterone, pregnenolone, thyroid, all these things that are critical for keeping your synapses going, are in short supply. There is a very different approach for those people.

DrDB:

Type 1.5 has some of both of those. That is glycotoxic. These are people that have both glycation of proteins and glyoxals, giving you the inflammatory piece, but they also have insulin resistance giving you the atrophic piece. We used to grow neurons in the Petri dishes all the time in our research, you always had to include insulin in there because it’s such an important trophic factor. So no surprise when you get insulin resistance, you are going to have less support for your synapses. Type 3, which is toxic. These toxins come in three groups, they are, inorganics like mercury or air pollution-related things. With the current California fires, this is a huge issue. Then secondly, organic toxins, glyphosate, formaldehyde, Toluene, benzene, things like that. Then the third group biotoxins, trichothecenes, gliotoxins, ochratoxin, things like that. Then Type 4 which is vascular. This is turning out to be very common. Vascular support to the brain, getting the appropriate blood flow, oxygenation, ketosis, all of these critical things, absolutely important and very commonly abnormal in Alzheimer’s and Alzheimer’s risk. Then the last one, Type 5, which is traumatic. So many people have head trauma as a contributing factor as well.

DrDB:

So if you can break that down and we do see, you know, there are doctors who most of their patients are getting better on this approach. And there are doctors who have very few of their patients are getting better on this approach. It really does boil down to exactly what you said: prioritizing. That’s really the advance over the years, as we begin to understand what are the most critical players for each person.

DrMR:

I can’t tell you how much I appreciate this. If I’m being a little bit candid, some of the pioneers of different models I’ve found, seem to have the constitutional way of analyzing information in which they’re always looking for the nuances and how to make things more complicated. They’re not looking for how do these nuances kind of connect back to a common unifying trunk. It’s something that, again I’m being really candid here, but it’s frustrating because when you double down on that model, you really shortchange the ability for clinicians and for patients to have the ability to more effectively apply what might be some really novel breakthroughs in that model. If you’re not looking for these patterns like you’re describing here, which I think are absolutely fantastic, you have more of a shotgun approach. We don’t know where to start, so let’s test everything and then let’s just start treating the tests. It’s nice in theory, but oftentimes the testing results are not able to be fully and literally translated from a clinical perspective.

DrMR:

So what ends up happening is you’re interpreting lab results, missing the juxtaposition to the patient context. Therefore you end up in some cases, mistreating the lab which results in mistreating the individual, which is why I absolutely love this model. Anything that you’d want to add to that?

DrDB:

Absolutely. We call this not a silver bullet approach, which is what you’re trying to do with a drug, but a silver buckshot approach, because you are covering more than one thing, but you are targeting each one of those things. So you shouldn’t have to cover too many things. I do think that the drug approach is going to be very powerful when it’s used on the backbone of the appropriate treatments. You may or may not have to use a drug with a person, but as you start to hit these other things and you target them with a precision medicine type of approach, a silver buckshot approach, then I think we’re going to kind of meet somewhere in the middle here where there’ll be some sort of relatively targeted, not too large contribution for each person that we can do to make a big impact.

DrMR:

Sure. The first component of your model or I guess the first component of your subtypes, the inflammatory type, certainly I think our audience really appreciates the impact of gut health on inflammation. We’ve also talked about how we can consider the oral cavity as the first section of the gut. So this is where periodontal health can be very important. Also, in some cases there can be dysbiosis in some instances that are a byproduct of mold exposure, but where someone can have dysbiosis in the sinuses. So this main mucosal tract is a huge source of inflammation. I certainly agree with that. I’m wondering, are you finding that that is the most common, is that why it’s considered Type 1?

DrDB:

So yeah, insulin resistance is probably the most common contributor to Alzheimer’s disease, as professor Ed Goetzl from UCSF showed by looking at neural exosomes. There are about 1.2 billion of these little nanometer vesicles floating around in every CC of your blood. They reflect what is going on in the brain. They derive from neurons and other cells in the brain. As he showed, there is the signature of insulin resistance in virtually everybody with Alzheimer’s disease. However, inflammation, as you indicated, what we call Type 1, is also a very common contributor. It is absolutely critical because the various cytokines that are produced during neuroinflammation are damaging to the brain. They are a part of Alzheimer’s. In fact, the amyloid-beta itself is part of the innate immune system. So just as we’ve heard from COVID-19, that cytokine storm is such an issue.

DrDB:

COVID-19 has essentially compressed all the risk factors of Alzheimer’s down into two weeks. So with people who have inflammatory Alzheimer’s, these cytokines do damage and, in fact, the amyloid-beta is one of these. It is not a cytokine itself, it is part of the innate immune system’s response. It does produce a downsizing response in the brain, which is what Alzheimer’s actually is, a downsizing response in response to specific insults, such as, chronic sinusitis, changes in oral microbiome, changes in gut microbiome, leaky gut. These are all critical. By the way, when the pathologists look in the brains of patients with Alzheimer’s disease, what they find is they find various organisms, including P. gingivalis from periodontitis, T. denticola, F. nucleatum, all from the oral microbiome. They find candida, for example, they find various mold species from the sinus. So absolutely there is much more communication, not only between gut and brain but between the rhino sinal microbiome and brain and oral microbiome and brain than we ever thought before. This is absolutely critical to address.

The Oral/Gut/Brain Connection

DrMR:

Sure. I think they’re obviously fantastic points. Just as one reminder for our audience. There was, I believe a meta-analysis published that found that oral probiotic administration can lead to a clinically meaningful improvement in periodontal disease or periodontitis. So not to say it’s all about probiotics or the gut, but certainly whenever we can find a simple measure or therapeutic like probiotics that may also help with oral dysbiosis, that can be helpful. I offer that because sometimes we don’t get the most straightforward opinion from dentists. Some dentists are more forward-thinking than others. In any given individual, you may get three different dental opinions. One person may say, everything’s fine. The other person may want them to do a 12-month mercury detox protocol for the one filling they had 18 years ago. You kind of have these extremes. So wherever we can help you have an intervention that could help with your oral cavity health, that doesn’t require a lot of testing and specific treatment. That’s a win. Of course, take this case by case, and if there is some kind of festering infection, making sure you see that through, but just a bit there that may be salient to those wondering if their oral health is where it should be.

DrDB:

Absolutely. This is a really important point. As you know, there’s a whole group now of oral-systemic specialists. These are people who are dentists by training but are now looking at the relationship between the oral microbiome and systemic illness. As you know, it’s found to play a role in atherosclerotic plaque in colorectal cancer. In cognitive decline, they’re finding these same organisms in the brain. This is a really important and emerging field.

DrMR:

Fully agreed. One thing to also point our audience to is Mark Burhenne who wrote an excellent book called The 8-Hour Sleep Paradox. He’s made some very interesting connections that dysbiosis in the mouth and other similar findings in the mouth, dry mouth, burning tongue, receding gums. Some of those may be due to nocturnal or nighttime mouth breathing that may be an indicator of underlying sleep-disordered breathing. So just keep your eyes and ears open to the fact that if there is a chronic issue or issues in the mouth, part of that may be due to mouth breathing, especially at night, which is kind of a double negative, cause not only does it throw off your oral health, but obviously it impedes your sleep quality. If you haven’t read Mark’s book, it’s a 100-120 pages, very simple read, but really loaded with action items.

DrMR:

So that’s something else for people to kind of keep in mind. You’re making a great point, Dale, that the mouth, it has kind of not been given its just attention. I think it’s finally starting to get the recognition that it deserves.

DrDB:

Absolutely.

SponsoredResources:

Let’s talk about one of my favorite tests for digestive health, the GI-MAP from Diagnostic Solutions, who has helped to make this podcast possible. Now if you’ve been reading any of the case studies that I’ve published in the Future of Functional Medicine Review clinical newsletter, you’ve likely seen that this test, the GI-MAP, is a test I frequently use in my practice. Why? Well, one of my favorite things about this test is it has excellent insurance coverage. So this is a few hundred dollars that I save patients. This lab is also CLIA certified, which is essentially the quality assurance bureau for labs. So it’s important that these labs are being monitored, not cutting any corners. That’s where you get your CLIA certification. Now, this test uses quantitative PCR technology. So it’s a DNA test. And you’ll get a good read on dysbiosis with this test because they will assess and report out various types of bacteria, yeast, and parasites including protozoa, worms, and amoeba. They also have some valuable and helpful clinical markers like calprotectin which can help rule in or out inflammatory bowel disease, and zonulin, a marker of leaky gut. So head over to DiagnosticSolutionsLab.com to learn more and to order your test.

Insulin Resistance

DrMR:

So question regarding insulin resistance. Well, first a comment, then a question. So my thinking is depending on the patient population you work with, that will be more or less of an issue. For me, in my clinic, we have many forward-thinking patients who are very well educated and they’re paying attention to sleep, to exercise, to diet, all these kinds of diet, and lifestyle fundamentals. So it’s much less common that we’ll see insulin resistance in our population. Now that’s more the exception than it is the rule in the United States. Just something for clinicians to be aware of, because my fear is in some clinicians hearing that, they’re going to force an insulin resistance solution to someone who may not be insulin resistant and they may overlook their gut health. So just something to be aware of because it’s most common, we have to offset that with the population that you’re working with and the more progressive and invested in their health someone is, ostensibly the less insulin resistance or insulin-resistant they may be. I did want to ask you how you’re defining that. One of the things obviously can be used is fasting blood glucose. Are you looking at that just being within range? Is there a nuance in terms of how you’re looking at that? Or do you juxtapose that with hemoglobin A1c, even though that can be confounded by other variables like inflammation. So, how would a clinician say yes or no, generally speaking, I should be considering insulin resistance with this individual in front of me.

DrDB:

Absolutely. So typically we are using HOMA-IR. So, you want to have your fasting blood sugar multiplied by your fasting insulin divided by 405.45 and that’ll give you an idea. We’d like to see it around 1.0. As it starts to drift up above 1.3, 1.4, and gets up to 2.0 and 3.0, You know, that is very significant insulin resistance. So that’s what we’re using. But you know, you bring up a good point for all of us, increasing dataset size, being able to look more and more carefully at what’s actually going on. If there’s a real suspicion, of course, an oral glucose tolerance test with insulin is the most sensitive, but for most people, you don’t need that. Just looking at the HOMA-IR is very helpful and having computer-based algorithms that work with us as physicians to allow us to get these much larger data sets. We now have an app that we’ve developed with a software company so that you can actually look at all these different things.

DrDB:

You know, that that is the future for all of us, to be able to look at larger data sets, to get better looks at people, better insights into the critical factors that are driving, in this case, the cognitive decline, but of course, for others in other areas. You’re absolutely right that gut health has been again, one of the most common things and getting the gut healed. So many of these people have leaky gut. Getting appropriate probiotics and prebiotics, all of these absolutely critical. And of course, optimizing microbiome. This has become such a huge field, the relationship between the gut microbiome and the brain, and, you know, Parkinson’s and Alzheimers. This is a huge issue. ALS as well. There are published papers on all of these areas.

HOMA-IR

DrMR:

Regarding the HOMA-IR, I’m just looking up a few things, cause I’ve actually been a bit critical of this measure in the past, but I’m certainly open-minded to that. I wasn’t clear on how well it translated clinically and it seemed like there may have been less data. Well, obviously there’s less data than using a fasting blood glucose. That doesn’t mean that fasting blood glucose is better, but that was part of my rationale was that it seemed like some of the nuances in how to look at HOMA-IR were still being worked out. That being said, I haven’t done a very deep dive on this. So that, if I’m correct, is fasting insulin multiplied by fasting glucose, which is, I believe what you said a moment ago.

DrDB:

Yes, divided by 405.45. So, the idea here is, you know, we do see a lot of people where we’d like to see their fasting glucose in the 70 to 90 range. You may have someone who’s got a fasting glucose of 85, but now their fasting insulin is 30. Okay. They’re working very, very hard to keep their fasting glucose where it is. So they actually have a very high HOMA-IR and they do have insulin resistance. Alternatively, as their insulin starts to fail, you know, their fasting insulin may be down at 1 or 2, but now their fasting glucose may be up at 120, that sort of thing. So that’s why I think it’s helpful to take both of those. As you said, also, hemoglobin A1c, we need to take that into account. So they all give you complementary information.

DrDB:

The other thing that we’ve seen a lot of by the way is with using continuous glucose monitoring, it’s been such a helpful thing. We see not only people who are spiking, often from foods that they consider to be very “healthy foods”, but also what happens is that they go to bed and they’re dropping down into the forties and fifties and they didn’t understand why they were waking up in the middle of the night. It’s not always obvious. It’s not always that they’re drenched in sweat or things like that. They’re waking up, not realizing they’re having hypoglycemic episodes, which is very bad for your brain as you know. Now with CGM, they’re able to say, aha, I need to smooth out my glucose curve. I need to lower the carbs in my diet. I need to increase the good fats in my diet, make sure my protein is mid-range, maybe one gram per kilogram, that sort of thing. If I can smooth out the curve, I won’t have those damaging hypoglycemic events in the middle of the night.

DrMR:

Right. That’s certainly something that we’ve talked about in the podcast before. One of the things that can be helpful for that, outside of just getting their diet more dialed in and finding the best macronutrient balance for them, at least what I’ve found is having some people have a snack when they wake up to help prevent or bring them out of that hypoglycemic event. That’s, I think, more of a subpopulation recommendation because as people become healthier and healthier, they should be able to maintain that, that fasting status throughout the night. So I want to be careful to say that’s more of a while we’re working on your metabolic health recommendation, not necessarily something that should be done in perpetuity, but would you have any concerns with employing that method in more of the acute phase application?

DrDB:

No, I think that that’s fine. I think the main thing is that we want to do everything to change the ratio. When you have cognitive decline or risk for cognitive decline, you have a lot of synaptoplastic signaling, things pulling back on your synapses. That includes all the things we’ve talked about. Much less synaptoblastic signaling, making, and keeping synapses. So we want to do everything to optimize your chemistry. That includes your gut health, of course, and your sinuses and your oral microbiome, and all the things that we’ve been talking about. We want to change that ratio. So, yes, we’d like to avoid these periods of hypoglycemia as well as have hyperglycemia

DrMR:

Related question for clinicians who are trying to incorporate more of this into their blood workup assessment, do LabCorp or Quest have a blood glucose with insulin that also gives you a pre-calculated HOMA-IR score, or do you have to just do the math? Not that it’s hard math, but you know, the easier you can make it on a clinician where they have it in the report the better.

DrDB:

Absolutely. Actually you can get the entire panel that we use. So if you look for example, dr. bredesen.com, you can actually go to mycognoscopy.com. We recommend, just like we all should get a colonoscopy when we turn 50, we should all have a cognoscopy at if you’re 45 or older. You want to look at this set of things. It includes your HOMA-IR and it calculates it for you. You can do it with that directly. Or you can do it through a panel. I’m not aware that LabCorp or Quest will calculate it directly for you.

DrMR:

Gotcha. Okay. Regarding diet, are you finding that everyone needs to be on a lower-carb diet? Or do you find that, and I’m trying to pose this question as precisely as I can, that some people may do better on a moderate or higher carbohydrate diet. That requires us to look, or at least what I’ve been doing is looking at their body composition and their energy levels. Some people, ironically, eat more carbs, less fat, and they actually feel better and they seem to have body composition improvements. That does seem to be more of a minority than the majority. I just try to always acknowledge a spectrum of dietary macronutrient consumption if or when it does exist so that people don’t feel like they’re shoehorned into a certain recommendation. Now that may not be the case from a cognitive perspective, but I’m just wondering what you see there.

How Diet Impacts Cognitive Function

DrDB:

It’s a great point. That’s where it’s so helpful to look to see with each person what works best. What we find is people who are willing to look and see how they are doing make changes, do the best. What we’re trying to do, again, we are coming from the test tube. So we’re looking at the molecular pathways? What is the neurochemistry that drives best cognition. In general, as you alluded to, the people who do best and the thing that’s been published the most for good cognition is what we call Ketoflex 12/3. So you’re getting people into mild ketosis, typically between 1.0 and 4.0 millimolar beta-hydroxybutyrate. If you like to use a breathalyzer, there’s a nice one from Biosense that you want to get above seven on the ACEs score, which measures acetone.

DrDB:

I don’t work for Biosense or anything, but we’re just looking for what works best. We’re agnostic. You want to get into ketosis. You can either be a vegetarian if you want, fine, or an omnivore, fine. If you’re going to do that, then you want to have fish, wild-caught fish. If you’re going to eat beef, it should be grass-fed beef. Pastured chicken, pastured eggs. One of the most common deficiencies in the United States is choline deficiency. We should all be getting about 550 milligrams of choline per day. It is the precursor for acetylcholine, the most important neurotransmitter in Alzheimer’s disease. It’s the one that’s critical for making memory. So being deficient in choline is not a good thing.

DrDB:

We want to optimize that. Then it is Ketoflex 12/3, because you want to have a minimum fasting period, 12 hours for the fast. If you’re APOE4 positive, you want to go up to 14 to 16 hours between when you finish dinner and when you start breakfast, brunch, or lunch. Then a three hour fast between finishing dinner and going to bed as a minimum, because you don’t want to have your insulin spiking while you’re going to sleep. So that’s generally the thing that works best for cognition. It does seem to be critical to get the ketone level up there because the ones who don’t get there, don’t do as well in general. The ones who get good ketone levels do better. So we recommend to people at the beginning, just take some exogenous ketones at the beginning. It’s not a problem for the first couple of months. Slowly we’ll help to get you into endogenous ketosis, which tends to work best. Now, as you indicated, a minority of people actually will do better on complex carbs. You know, that’s fine. That’s the kind of group that Steven Gundry talks about, they do very well. So as you said, for some body types and for some personalities, that may be better, but in general, we want a high good fats, mildly ketogenic, plant-rich diet with appropriate fasting and appropriate fiber. Fiber is a huge part of this as well for its detox, for its glycaemic effect, for its lipid effect, for its microbiome effect, for all of these things it can be helpful.

Atrophic and Vascular Type

DrMR:

Shifting gears, just for a moment here, looking at the other components of the model, the atrophic and the vascular seem like they would have a lot of overlap in terms of exercising, fasting, maybe sauna therapy. Can you tell people a little bit more about these, what they might want to be on the lookout for, and certain things they may want to put in to practice to help mitigate any imbalances they have there?

DrDB:

Absolutely. Many people feel as they get a little older, “well, I’m kind of expecting it, I’m a little older now, I’m not expecting to do as well as before”. This is something where functional medicine, I think, has addressed it so well. It may be that your homocysteine is “normal”, but it may not be optimal. Unfortunately within normal limits simply means within two standard deviations of the norm, it has absolutely nothing to do with best physiology. So we should all be aware that optimizing our physiology is going to take getting these things into the right range. It’s all the various hormones we talked about and it’s nerve growth factor and brain-derived neurotrophic factor. The good news is, in our arsenal now we have the ability to alter all of these things. We’ve been told over the years, unfortunately, that there’s nothing you can do about cognitive decline. It turns out, thankfully, nothing could be further from the truth. There is a tremendous amount that you can do about it, and absolutely you want to optimize these various things. As you indicated earlier, as you get healthier, these things tend to get better. A good example, one woman who had a very low fasting insulin and a high fasting glucose, as she started to improve things, not only did her glucose come down, but her fasting insulin moved up and came into the normal range. She was just not able to generate the insulin previously. So all these things tend to improve. So that’s Type 2, the Atrophic type.

DrDB:

Type 4 is a little different in that it is energetics. You need to get to the far reaches of your brain and surprisingly, many of us are not doing that effectively. That’s one of the reasons that sedentary lifestyle is so bad for your brain. And so you have to have this critical triad. You have to get the blood flow itself. Again, with some atherosclerosis, that’s going to interfere with that. You have to get the oxygenation there. We find so many people, where the doctor just didn’t check, people weren’t aware and they’re dropping their oxygenation at night when they are sleeping. And so they’re coming down from 96 to 98% where they should be, down into the 80s. We’ve even seen people into the low seventies, people who didn’t realize that they had sleep apnea and may not even have diagnosed sleep apnea, but they may have upper airway resistance syndrome or other reasons to drop their nocturnal oxygenation. Of course, now, with all the things we can, we can check our own nocturnal oxygenation very easily. You can buy an oximeter or….

DrMR:

Let’s go into a little more detail there. I would actually be really curious to hear what you’re finding because this is kind of a specialized field all in of itself, but how can people get a good read on their sleep quality? Perhaps sleep quality needs to be assessed and also oxygenation at nighttime needs to be separately assessed. Of course, a sleep study is sometimes just recommended as if it’s an easy thing, but then in application, there are some major hurdles with some people’s insurance not covering that, many people don’t want to go through the labor of that. An Oura ring seems like a decent device to get some preliminary data. I know there’s the HST (the Home Sleep Test). What do you think is good practical advice to the patient or clinician who wants to get a preliminary assessment of quality and/or oxygenation at nighttime. How does one assess that?

DrDB:

Yeah, great point. So usually for a sleep study someone will want to know if you have symptoms to suggest that you have sleep apnea? So that’s one way to go. If you don’t have that, as you mentioned, there’s the Oura ring. There’s also something called BEDDR. The new Fitbits also have this capability, the new Apple watch that just came out looks at oxygen saturation. So everybody is realizing now oxygen saturation is important. I think some of this has come from COVID-19. During the day, if you want, you can check your SPO2, your oxygenation status, on your iPhone. There’s a simple app to do that. So many of ways to do it, but you do want to know. It’s a critical piece, getting the oxygenation. Then the third part of that triad is getting the ketones. You have to have something to burn. It’s just like, if you’ve got an outpost in Alaska, you’ve got to get to the outpost, you’ve got to bring the right things to the outpost and they’ve gotta be able to use the things that you brought to the outpost. This is absolutely a critical region for Alzheimer’s. A very common contributor to cognitive decline and also to people who have “normal” cognition, but could actually do a little better with optimizing those parameters.

DrMR:

Gotcha. My apologies to the audience. There’s construction going on by my office. So you may hear some background noise that I’m trying to mitigate, but failing since it’s literally right outside my window.

Accuracy of Self Monitoring Devices

DrMR:

What is the accuracy of something like a Fitbit for oxygenation? It would seem to me that we need a more complicated measure, although I’m happy to be proven wrong on that, but are those devices fairly accurate in that measure?

DrDB:

Of course, if you want the most accuracy, you’re going to want to have a formal sleep study, no question. These things are all approximations, but they do get you in the right range. In fact, since we’re looking for 96 to 98%, if you’re sitting down at 75 or 82 or something like that, very likely that there’s a problem. Of course, they also give you a first-order approximation so that you can then follow up and say, okay, I now realize that this is an issue. I need to look into it further.

DrMR:

Gotcha. So it doesn’t necessarily have to be an arduous, expensive, uncomfortable process to at least get a preliminary assessment.

DrDB:

Exactly. I think more and more the quantified self is becoming so important and so helpful. Just kind of knowing where we all stand. You know, now we can measure our ketones and we can measure our glucose and we can find out about our microbiome and we can find out about our genome. It’s just amazing what can be done that wasn’t available 10 years ago. We can look at our oxygenation. We can look at the number of steps we’re taking and our blood pressure and our heart rate variability, all these things so that we can really do a much better job of adjusting and optimizing our physiology. This is a huge field going forward.

DrMR:

Yep. With the Oura ring, I’ve shared my story on the podcast where I was probably, a bit in denial that going to bed before 11 pm had as measurable of an impact on sleep quality as it did. But the Oura ring really exposed that. I was really kind of coaxed into being better about getting to bed at an earlier time. That leads to a question I wanted to ask you. I’m not sure if you are looking at enough Oura data to have an opinion here, but is there a certain sleep score that you are looking for? A number where you should be above this range and if you’re not that’s cause for concern. That seems a little bit more difficult to adjudicate. It does seem when looking at the app, you want to be at least an 80 or above that.

Speaker 3:

That’s when you kind of get into the blue sky background and at least the app is suggesting that this is where you want to be. I look at that as beneficial to know on the one hand on the other, I don’t want to set a goal for people that may be extremely hard for most people to hit and then create angst. So what are your thoughts there in terms of what people should be looking for their sleep scores to be? It’s a great point. So this is exactly why we created the ReCODE app. It takes all these data, so we’ll be able to see over time, who’s doing the best with their cognition, who’s improving, who’s declining, who’s stable, et cetera. We have data on, things like glucose and toxins and things like that. We don’t yet know about the Oura ring. There just hasn’t been enough data. There hasn’t been enough input to know what’s going to be critical for cognition. So I think you bring up a really good point. We don’t have the data yet. This is why, over time, we should know this exact question.

DrMR:

Well, I’ll be very curious to see where the consensus forms for that. That being said, I think we have some rough approximations that people can look to. The one thing I would offer to people is just not to be fanatical about any one measure. Look at these things as biofeedback to help you guide your decision making, but don’t get overly angst if you can never get above 85. We want to use these things for benefit and for informing our practices, but not to cause stress or worry or what have you.

DrRuscioResources:

Hi everyone. This is Dr. Ruscio. In case you need help, I wanted to quickly make you aware of what resources are available to you. If you go to drruscio.com/Resources, you will see a few links you can click through for more. Firstly, there is the clinic, which I’m immensely proud of. The fact that we deliver, cost-effective, simple, but highly efficacious, functional medicine. There’s also my book, Healthy Gut, Healthy You, which has been proven to allow those who’ve been unable to improve their health, even after seeing numerous doctors, be able to help them finally feel better. There’s also our store where there’s a number of products like our Elemental Heal line, our probiotic line, and other gut supportive and health-supportive supplements. We now offer health coaching. So if you’ve read the book or listened to a podcast like this one, or are reading about a product and you need some help with how or when to use, or how to integrate with diet, we now offer health coaching to help you along your way. And then finally, if you are a clinician, there is our clinicians’ newsletter, the Future of Functional Medicine Review. I’m very proud to say, we’ve now had doctors who’ve read that newsletter, find challenging cases in their practices, apply what we teach in the newsletter and be able to help these patients who were otherwise considered challenging cases. Everything for these resources can be accessed through drruscio.com/Resources. Alrighty, back to the show.

Head Trauma

DrMR:

One final topic I want to cover. There are many more questions I could ask because there’s a lot here to unpack. I think this model is just fantastic, but head trauma is something that we have talked about on the podcast a few times. One of the things there does seem to be a subset of with chronic digestive ailment patients is a history of head trauma. There’s also a history of emotional trauma, a little bit different, but just to quickly acknowledge it for the audience, emotional trauma may really lend itself well to something like limbic retraining therapy, but there’s also head trauma.

Speaker 1:

And we discussed this with Dr. Titus Chiu who wrote the book Brain Save and has a really good kind of home-based neurological rehab plan for those who have had head trauma. For some people that can really be the difference between success and failure. We also have to be careful because some circles in functional medicine proclaim that everyone with IBS has a vagal nerve problem and has people doing all these exercises that don’t really have any historical evidence to support that there is a problem there. So we want to be careful not to force a brain-based problem onto a non brain-based population. Again, for those, especially with the history of head trauma, this really tends to land for some people. Any kind of pearls regarding head trauma?

DrDB:

Absolutely. So, you know, there was a classic paper years ago by Dr. Gareth Roberts. He looked at people who had very significant head trauma and who ended up dying of their head trauma within a week or two. They had massively increased amyloid. The very thing that we associate with Alzheimer’s was actually brought out by head trauma, which had not been realized before. So when you have head trauma, part of this response that you have is the production of the very thing that we associate with Alzheimer’s disease. Now, for most people, they end up clearing that over time, but it tells you why these people are at increased risk for Alzheimer’s. So if you do have a history of head trauma, everybody, you know, everyone who’s had traffic accidents, who’s had some head trauma, everyone who’s played football, and everyone who’s had any sort of significant, repeated, even mild head injury should be on a prevention protocol.

DrDB:

We develop one that’s called PreCODE for prevention of cognitive decline that you can get on, but there are others. You want to get on things that absolutely will optimize the ability to reestablish these connections because there is a tremendous amount you can do about it. Just as we’ve been told there’s nothing you can do about Alzheimer’s, we’ve been told about head trauma. But there is a tremendous amount that can be done for cognitive decline associated with head trauma, whether it turns out to be Alzheimer’s or not. The earlier the better. You want to intro increase your trophic factor support. So actually things like whole coffee fruit extract, which increases BDNF, exercise increases BDNF. Things like ALCAR (acetyl-l-carnitine), which increases nerve growth factor, making sure that your hormones are optimized, making sure that your vitamin D is optimized. Obviously, this has come out in COVID-19. So important to have optimal vitamin D, optimal zinc. This is the same thing for head trauma. Head trauma is a lot like Type 2, the atrophic because you’re not supporting those synapses. In this case, of course, because of physical damage to them instead of chemical damage.

DrMR:

Now with the PreCODE plan, would you say, and I’m asking this question mainly for the providers, let’s say you are a provider and you’re working on many of the things that are listed in the plan, many of these foundational health applications, nutrition, inflammation, blood sugar regulation. Would the PreCODE plan be a good referral or would there be a lot of redundancy? Should a clinician be looking for, if they’re looking to complement their therapeutics with something that’s head trauma-specific, would you recommend someone finding a neurologist or a chiropractor neurologist or someone who would hone in and focus on that specifically, or would there not be much redundancy with the PreCODE?

DrDB:

Good point. So PreCODE is specifically for people who are asymptomatic. So this is truly a prevention and you can get it directly. You don’t even need to go to your doctor. You can get it directly. Go to myprecode.com and you’ll get a 60 plus page report that’s very much like the Boston Heart Study would be for the heart. This is the analogy for now. This will tell you, what are your major risk factors for cognitive decline? Here’s how to address them. So that’s critical for anyone who has a family history, children of people with Alzheimer’s, people with a family history of dementia, people 45, anyone who’s concerned about cognitive decline because it’s such a common problem. About 45 million of the currently living Americans will die of Alzheimer’s if we don’t do something about it. So prevention is step one.

DrDB:

For those who truly have symptoms and who have had significant head trauma, then actually ReCODE is much better. That’s assists in reversal of cognitive decline. You can get that as I mentioned, mycognoscopy.com. That does go into much more detail. It does look at some of these critical things like gut health and like glucose. So if you’ve done all of these things, then you may want to look at, what do I want to do in addition. ReCODE will tell you what are the things that are most likely to cause your decline in the future? Because of course, if you’ve had head trauma, these others are still contributors. If you’ve got head trauma, but you’re also exposed to specific toxins you’re unaware of, or you’re actually dropping your oxygenation at night, that you’re unaware of, things like that. These are things that can be nipped in the bud, that can be optimized to give you a better outcome for head trauma-related, cognitive decline.

Episode Wrap-Up

DrMR:

Fantastic. Fantastic. Well, Dale, this has been a really insightful call again. I just can’t tell you how much I appreciate the fact that you’re now identifying these subtypes because I think, as the field progresses, we need to be more and more efficient with our care. This seems like a great kind of heuristic to help clinicians parse all the components of the model. So just fantastically well done. Is there anything you want to leave people with and please mention again, any new websites or books that you would like people to look at if they’re looking for more information?

DrDB:

Absolutely. I think that the key here is we can all work together to reduce the global burden of dementia. You know, let’s make, Alzheimer’s a rare disease. It can be. With what we know now, and you can find more information either in the book that just came out, which is called The End of Alzheimer’s Program. The first book was The End of Alzheimer’s. It’s now available in 32 languages. The new one, basically people had asked for more details, what websites, what workarounds, where do I go? What do I get, et cetera? So we tried to put all of that into the second book. The End of Alzheimer’s Program just came out from Random House a couple of weeks ago. Then you can go to mycognoscopy.com if you’re interested in prevention, myprecode.com. It is a less extensive program and actually does a great job with prevention without having to do a ton of different things just as you indicated earlier. So thanks very much, Michael. Thanks for all the great work you’re doing. I really appreciate it.

DrMR:

Yeah. Thank you again. It’s been a real pleasure.

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