Facebook Live: COVID and Cognition

Apollo Health’s Chief Science Officer, Dr. Dale Bredesen; Chief Health Liaison, Julie Gregory; and functional medicine expert Dr. David Clawson discuss how our “threat load” can predispose us to COVID and dementia.

We’ve included a complete recording of the session and a full transcript below for your convenience. 

Watch here:

Transcript:

Dr. Dale Bredesen: Hi, everybody. Happy holidays. I hope everyone is doing well. It’s a tremendous pleasure today to have Dr. D.R. Clawson here. D.R., welcome. Thank you so much for joining Julie and me.

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Dr. David Clawson: Thanks for having me.

Dr. Dale Bredesen: First, a little background on Dr. Clawson. He is a tremendous functional medicine expert, and he has been in the area of a rehab medicine for years. And if anyone has seen “The Locker Room” on YouTube, great thing, I recommend it highly, check out “The Locker Room.” He has some tremendous lectures, one for example, on neurodegeneration and stress and threat in the neuroanatomy of this and the neurochemistry of this, really well worth listening to. And so we thought it would be a good idea, really timely, because we’ve got the Omicron variant that’s beginning to affect people, just had the first case in California documented, as everyone knows, there’s obviously concern about this.

There’s a tremendous amount of stress. Of course, we’ve got holiday stress that everybody has. Of course, we’ve got the pandemic stress, so many different areas. People are under tremendous amounts of stress, and we know that this affects cognition. And in fact, you just look at people who have high cortisol. They actually have shrunken brains. We see people, for example, who have especially the toxic form of cognitive decline, where literally as their stress goes down, their cognition goes up and as their stress goes up, their cognition goes down. So it’s such an important part. And Dr. Clawson is an expert in this area as well as other areas. So D.R., If you could tell us a little bit about your background. I know you were a football player many years ago at University of Washington, so obviously a very, very accomplished athlete, but tell us a little bit about your background since then and how you got into the area of functional medicine.

Dr. David Clawson: Well, I went to med school with the idea that I was going to be a sports medicine doc. And along the way, I discovered a small specialty physical medicine and rehab. I think I was the first med student in our school to go into that specialty and physical medicine and rehab really focuses on chronic illness, disease and associated impairments and disabilities. So I’ve spent a little bit of my career doing sports medicine, but almost as a side and a lot of my time has been spent taking care of patients in the hospital, doing consults in the hospital and doing follow ups in clinic. And as I’ve watched the presentation of chronic illness and disease now for 30, some odd years, more than that, that’s scary.

And I just have a, I think, slightly different vantage point, a different viewpoint, on the underpinnings of chronic illness and disease and neurodegenerative disease, but other diseases as well. And I think there’s a there’s a common thread for me. I frequently thought about the fact that we need to have a subspecialty called a “threatist,” somebody who studies a threat, is very good at putting threat under a microscope and dissecting it and resecting it and treating it because fundamentally, I believe that every acute and chronic illness and disease is related to threat and chronic illness and disease in particular to a chronic threat response. And we are not very good at looking at that. In fact, when you review many charts from multiple specialties, you’ll frequently see that nobody’s really taken a good generational history, family history, social history.

And so we don’t understand the extent of threat. We think of things like COVID, a virus, or a bacteria, or something that, but threat comes in many forms, spiritual, social, financial, bodily threat, past traumas predictive codes, generational threat that gets wired in or coded in epigenetically. So we have all of this going on inside of us activating this threat response, which we don’t understand very well. We don’t understand the threat load, and we don’t really understand the response very well. So that’s because what I have done in the later part of my career is to dig into that. So instead of looking at… If threat is the root of all illness and disease, we’re out there on the branches treating the flowers and the buds that come out from the root of threat. We’re not in the dirt treating the root of the problem.

Dr. Dale Bredesen: That’s a great point. And I know this is very complicated. There are all sorts of neurochemical pathways and various neuroanatomical pathways, but maybe let’s dive into a couple of them. One of the points that you make is that in medical school, we’re all taught about the fight or flight response with adrenaline and noradrenaline, norepinephrine, this thing. But you point out that it goes beyond that, there are multiple approaches. So maybe if you could say something about the four different events, it’s not just about fight or flight.

Dr. David Clawson: Let me try to cover something really quickly to put it all into perspective. In the 20th century, we started to understand the autonomic nervous system earlier in this in that century really, and also understand the hypothalamic pituitary adrenal axis and that’s still where we live. We got the mono immune theory in the ’80s with listening to Prozac and everything, but there’s something that’s going on deeper in the soup, in the interstitium the body and that’s intercellular communication, which is much older, probably 4 billion years old intercellular communication in primitive organisms. And our vascular tree, our hormonal network and our neurologic tree, are at best 500 million years old.

So that’s where we look, that’s where we treat, but we have to start looking at a molecular level and at an intercellular level and an intracellular level, because we also have to understand what mitochondria and the internal organelles of the cell are doing when they receive a threat signal. So just layering on that. I think for me, there are fundamental phenotypes that we have. And so phenotypes are reflected in our physiology, the transcription of our genetic code as projected into our physiology. I see that we have technically two threat phenotypes that have subtypes. So the fight or flight response is a mobilization response. You can punch the tiger in the nose, or you’re going to run. That’s sympathetic nervous system being really activated and the next expression or the next response we have to severe threat is a protective response. And I characterize it as threat two, but it’s a phenotype of immobilization where we’re going to submit, surrender, curl up in a ball, hide, get very quiet and worst case scenario, we’re going to faint.

And I call that falter to faint. So we have this fight, flight, falter, faint physiology, all of them designed for our survival. That’s why we have them, so that we can pass our genetic code forward. Anyway, I’ll let you jump in there.

Dr. Dale Bredesen: That’s a good point. Well, you mentioned something I think is very relevant, which is intercellular signaling and threat because one of the interesting findings is that if you go back, you look at very, very early in evolution things like sea squirts that are very far down the evolutionary trait when they interact, if they decide that they don’t want to interact, they actually secrete an amyloid substance as a barrier, basically saying, “I’m not going to interact with you.” And then interestingly you move up to bees, honeybees, if they get invaded by a rat into there, for example, they make propolis and they literally put the propolis around a dead rat. Again, it’s a barrier, it’s an amyloid-like antimicrobial barrier. And so when our brains make amyloid, to some extent, they’re saying, “This is an antimicrobial barrier, you cannot come and bother me. I’m going to sacrifice some of my synapses and some of my space, but I’m going to create this barrier.”

And so the idea of just getting rid of that and everything will be fine is, I think, somewhat naive. We want to go back to what’s actually causing that response. And you talk a lot about the cytokines and about the fact that these are catabolic. This is associated with shrinkage. And what do we see on these brains? We see shrinkage in the volumetric studies. So if you could talk a little bit about cytokines and catabolism and how it is that these things, how is that these things are actually trying to help you, but of course, in the wrong setting, they can be damaging?

Dr. David Clawson: And even I’ll go back even just a little bit further back to our very primitive world, about 3.5 billion years ago, when we start having populations of single celled organism bacteria, and the things of life are a boundary to hold your stuff and a metabolic process so that you can run the mechanics of life, whatever your life is, and then a reproductive process. And then the very next thing that life needs, particularly in a competitive world of full of conflict, whether it’s today or in the soup, 3 billion, 4 billion years ago, is a defense mechanism. So primitive life is based on detecting whether you’re under threat or you’re safe. So bacteria do the same thing. They signal each other with small peptides 10, 12 amino acids to say, “Hey, danger is here,” or they’ll say, “Hey, we’re safe and by the way, there’s a chunk of food over there.”

Once they reach a critical level, they’ll all go to get a good food source together. They bond, they form a colony, and they start to specialize within that colony. So the cells on the inside are chewing up stuff, and they’re passing stuff to the outside of the colony. And outside of that colony is creating a sugar crystalin, maybe amyloid, layer, but a protective layer. So even in primitive life, you see this determination of threat or safety, you see those same types of phenotypes and interestingly, you see prosocial, and when things get bad bacteria, cut bait. They split and they actually undergo fission to get their genetic material split and then they separate. So under threat, even bacteria go into asocial behavior and isolation.

And so just going back to their little peptide signalers in between them, our modern-day version of that, I tend to focus on the cytokines because they seem the most pure in terms of threat and safety for intercellular signaling. They seem the most pure to me, but there are obviously other signalers in the body to compliment systems involved in everything, but they talk to the cells. So we focus on fight or flight being triggered someplace up in the amygdala and passing through the autonomic nervous system. But the reality is down at a cellular level, any single cell that senses something’s wrong, things like extracellular ATP, or bits and fragment of other cell or bits and fragments of a bacteria, they will actually start the threat response and activate this release of cytokines that then signals throughout the entire body.

So these cytokines are really interesting because we know them primarily as being pro-inflammatory. So they activate the inflammatory response and the immune response. And I’ll make the point those are not the same. They will diverge. You can have very low immunity and still have relatively high inflammation. But the other thing the cytokines do, the threat cytokines, is they change our metabolism. They literally change us physiologically. Our mitochondria go from ovoid and doing oxidated phosphorylation to undergoing fission and doing glycolysis. So we have a dramatic loss and energy production under threat. And we need a lot of few for threat, because if you have mitochondria that are producing 18 ATP per molecule of glucose, you’re producing a ton of energy, but under threat, if you do this and you’re producing one ATP for molecule of glucose, you need more fuel for the fight and the flight.

And that becomes really important. And just an aside, that oxygen we’re no longer using for oxidated phosphorylation, we can convert into reactive oxygen species, which amplify inflammation as part of a defense response against pathogens. So we have very low energy production, and we need a lot of fuel. And so the body has to prioritize things. It has to prioritize the things that are needed in threat to escape the tiger, which is the muscles, the diaphragm, the heart, and the things that get marginalized and relatively shut off are things the gastrointestinal tract because it’s not time to stop at McDonald’s when you’re being chased by a tiger. And it also shuts down the reproductive system, so sex hormones are shut down and oxytocin is shut off in favor of things like aldosterone and cortisol and vasopressin that activate us and inflame us.

And obviously cortisol helps to produce a lot of fuel in terms of glucose, but where do we start getting that fuel from when we can’t stop to eat? We take it from our tissues. So let’s fast forward a little bit to the brain. The last part of our brain to form and organize and the newest part in terms of evolution is the human neocortex, the neocortex. And it’s massive. And it’s why I have a landing strip for a forehead, a lot of air, but that part of the brain is very distinctly human. The neocortex allows us… The dorsal lateral prefrontal cortex is planning and judgment and creativity making constructs. And the medial prefrontal cortex is part of our social engagement system for compassion, bonding, empathy, our language center, our very advanced language center is essentially symbolic.

Communication is not necessary in fighting a tiger, and we don’t need to bond with a tiger. We don’t need to be inventing a wheel. We need to be reactive and impulsive even to escape the tiger. And the other thing is declarative memory. The part of memory that we use to play Jeopardy is not an advantage in having a discussion with the tiger. So we down-regulate those parts of our brain first, the last to essentially form as we age and the last in our evolutionary process. And I think what happens, not only do we down-regulate it by decreasing blood flow, but the cytokines directly affect what’s going on from a metabolic process. So you can start to see program deconstruction apoptosis to use those resources for fuel if either you’re in severe threat, like sepsis, you’ll see that in sepsis or a long, long protracted period of chronic threat, you’ll start to see some degeneration in the neocortex first.

Eventually it’ll get to other parts of the brain. And I think it’s just all part of a strategy of an organized threat response. And the problem isn’t the threat response, the threat response is working as it should. The problem is the chronic threat load.

Dr. Dale Bredesen: It’s a good point. There’s several points there. One of them, obviously, it’s having a short period of stress with resolution is not a problem. It’s that chronic activation. And as we often talk about and as you pointed out in your lecture on YouTube, you have a cytokine storm that is killing people with COVID, but it’s a cytokine drizzle that’s killing people with Alzheimer’s. You’ve got this mild, this production of cytokines for decades, unfortunately. The other thing is it’s interesting when what you’re talking about is very much relevant for the cellular change in mode, which is called the epithelial mesenchymal transition, the EMT. You go from a situation where it’s mostly oxidative [crosstalk 00:18:53] to where it’s mostly glycolysis from where it’s mostly a cooperation and differentiation to where it’s every man for himself. And so it’s literally switching modes.

And as you say, you’re switching modes because of a threat. So this fits very much with what we see with cognitive decline. So the question then becomes in terms of translation, because we’re always interested in translating the basic research into what does that mean for us every day? What can we do? So for people who are beginning to have cognitive decline, or who’ve had it for some time and are under a lot of stress, and we certainly see this all the time, especially with the people who have type three or toxic Alzheimer’s, how can we help them? Should they be looking at their heart rate variability? Should they be doing biofeedback? And I know certainly Julie has written about this extensively, Julie and Aida. What’s sorts of things can people do, practically speaking, to reduce this effect, to reduce this activation of the amygdala, as you mentioned, and all the stuff comes back to what you’ve talked about with polyvagal response and things like this. So what sorts of things practically can people do to support their cognition and to address this ongoing stress and threat?

Dr. David Clawson: So, my recommendation is to, number one, do a complete assessment of their threat load. Now this is a massive undertaking, because threat comes in physical forms, so you want to make sure that you’re not being exposed to pollutants and toxins and microorganisms that are going to stress you, but also you need to have a good food supply, a healthy food supply, without a lot of artificial stuff, because our body it recognizes artificial stuff like, “I don’t know what that is,” and it produces inflammation and it essentially produces the threat response. And you need to be in a so a safe environment. You need to have a warm bed and warm food and a warm shower thing.

So those are all parts of it. And I think the other thing that I lump everything under spiritual threat, which is when we’re thinking about… A lot of what we talk about with the tiger is either anticipated injury or actual physical injury. But when we get into spiritual threat that needs some evaluation too. So emotional injury is a big deal and obviously adverse childhood events or even generational trauma. So for Black America you may have 400 years of generational trauma that you’re not going to be able to fix that, but I think you have to be aware of what that is and have a way to somewhat decode that and move beyond it. And if you are actually living in an environment that is emotionally or psychologically unsafe you need to do something about that as well.

And then we have the societal structural issues of things like living in isolation, perhaps overcrowding, disenfranchisement, prejudice, discrimination, justice. I think we’re seeing the effects of disenfranchisement, like when we’re seeing these school shootings. But those things need to be addressed more on a societal level and even on a political level, but where I think it really gets tricky for us beyond that is some of the negative narratives that were given by other people or negative narratives we’ve created by ourselves. They activate the stress response and then the one dynamic that I see that is problematic, that is really unique to humans, we’re not a very good species, right? We’re not very strong. We’re not very fast.

We don’t have a very good coat of fur, whatever. So we really, really, really need each other. So the social engagement is part of this big prefrontal cortex, the social engagement system is really important for us. So it’s really important for us to figure out how to belong to the tribe, to stay within the tribe and that causes … So we’re going to get into Freud here a little bit weirdly, but if you think about our emotions, our physiology, until they get to the cortex and we’re aware of them, then they become our feelings. But emotions are just physiology and emotions are designed to get us to do something, emotion. So sometimes it’s to curl up in a ball and hide or fight or flee, but they’re designed to get us to do something.

But if our social constructs are such that they’re not going to allow us to recognize those emotions coming through, so it’s a little bit of the id and the super ego, right, the child and the parent, and every time an emotion impulse comes through the prefrontal cortex slaps it down and says, “No, don’t do that. You’ll be embarrassed. That would be shameful.” And we get this conflict, which is essentially repression or suppression, but a lot of times we’re not aware we’re doing it. We get a repression system going, and that creates conflict and conflict registers in that anterior singlet gyrus, and then goes you get this… It’s more global than that, but then it activates the amygdala and the whole threat response. So I think one of the biggest viruses on the planet right now is our inability to allow emotions to come through because of all of these constructs, which we need, some constructs that integrate with the tribe.

And those repressions make us really sick and doctors and male doctors, we’re just trained in repression. And so there’s a toxicity to us and it’s really hard for us to treat our patients when we don’t even recognize our own personal physiology, but I think that’s… So somatic integration and awareness and emotional and awareness, free expression and play, which is a form of free expression, those types of things are totally underrated in our culture. And we need those to detoxify ourselves. So there’s a whole paradigm that crosses all of the potential threats and we should be doing a better job with all of them.

Dr. Dale Bredesen: Interesting. So let’s talk to Julie for a minute. So Julie, could you weigh in? I know with your website, with the thousands of people you interact with, and of course, with your own practice, do you have favorite areas in terms of addressing stress and threats? So you’ve got people who are in the middle of a pandemic who have depression. As they say, depression and insomnia and anxiety, these are all part of systems that aren’t quite making it. You’re on the borderline. This is what stress is all about. So do you have favorite forms of meditation or favorite forms of biofeedback, or tell us a little bit about the things that you feel have worked best for you and others you’ve interacted with on your website?

Julie Gregory: Sure. What’s been most helpful for me is my daily outdoor walk, spending time in nature. All day long, I’m so busy achieving things — attending this meeting and taking this phone call and finishing this project. But when I go outside, I spend at least an hour a day in nature. I’m just being, and it’s amazing. I use this as my exercise period when I’m walking interspersed with running, but while I’m doing this, I actively practice mindfulness. If I begin to get negative thoughts that creep up, if I start ruminating about past events or worrying about future events, I stop myself and I just focus on my senses and I feel the weather on my skin. And I see the beauty around me. I hear nature and it just completely relaxes me. And especially during COVID, this has been my daily vacation, my daily gift to myself.

We recently had a meeting, a support group meeting at ApoE4.info, and we asked everyone in the community to talk about their inner practices, because we recognize that stress management is so important. And the things that came out were just so beautiful. There was one woman who was an ApoE4 homozygote, who was in her eighties and she’s doing amazingly well. Her cognition is just perfect. And she said meditation was extraordinarily important to her. Like all of us, she uses her breath to get into the meditative state. But she also uses this guided imagery where she would imagine her breath was a rope, pulling her deeper and deeper into the cave and it allowed her to turn inward and get this sense of calm. And that was something that she really looked forward to every day. So it was really interesting to hear everyone’s practice.

Dr. Dale Bredesen: Yeah, this is fantastic. And obviously you have an outreach with so many people. One of the things that’s been interesting to me is just seeing heart rate variability, now that the wearables are telling us, giving us so much more feedback. You can really see, and I’ll see before I’m ready to go into a meeting, the heart rate variability be way, way down. And then with just some breathing exercise now it’s way back up again. And it’s amazing how you can really follow these things. So this is very, very interesting.

Dr. David Clawson: I’ll comment that I think that heart rate variability, measuring neurotransmitters and cytokines is challenging because they are intercellular communicators. They’re not really in the blood. They’re a little bit in the cerebral spinal fluid, but heart rate variability is probably our best indirect way of measuring cytokines. So you take rats and inject some interleukin six or tumor necrosis factor alpha into the nucleus tract and solitarius, you will tank heart rate and variability right away. You’ll create a shock syndrome. So I totally support what you’re saying as using that as a gauge to where we are. And I also, on Thanksgiving, we were talking about forest bathing. I think we have intercellular communication going on there that’s extrasomal.

Dr. Dale Bredesen: I think this is so important. I was thinking when Julie was talking about that, this is the American version of Shinrin-yoku. So it is getting people out and doing and some forest bathing, and it is something where we run across people all the time where not only are they having the problem with being indoors too much because of stress, but now they’re not getting outside for just walking among nature, but they’re also staying inside and they’re getting exposed to more mycotoxins. They’re not outdoors and getting exposure to cleaner air, et cetera. So we’ve got some great questions here and let’s go through some of these. And I want to just start with one here from Valerie who says here that this man, she’s talking about you, D.R., this man needs cloning, fancy talking about the toxic male MD construct, brave and necessary.

So D.R., if you consider being cloned, Valerie, would see more people like you, which is fantastic. So thank you, Valerie. She also says Omicron has reached her area too. That’s unfortunate to hear, it’s starting to seep into places around the world. She said, I’ve just recently been tested for adrenaline at rest, as I kept having PTSD to type overreactions. And again, this is part of the pandemic life that we’re all facing now. I think everyone is going to be dealing with more stress, more, more threat, more of these PTSD type overreactions and D.R., in your practice, what do you tell people who are just saying, “Look, I’m under stress all the time now because of the pandemic?” What sorts of things do you do for them?

Dr. David Clawson: Well, that’s where it’s a little bit challenging for me. We have maybe an abbreviated version of this a discussion, but one of the things that I make some self-help referrals for them to depending on what they’re presenting with, whether it’s the Curable app or Schuebener’s stuff, or referrals to psychologists to help with it. But by and large, one of the things that I do literally at the bedside when I talk to people is I ask them what they’re holding? What are they holding? Where is it? Is in their chest and what is it? And ask them to try to bring it forward and release that sense of fear or emotion in an expressive way.

And so and I think there are psychologists that are trauma informed that do a really good job with threat in general, but I asked them to do Pennebaker writing as free expression, or I asked them to just put on music and wiggle with the music, let it go, whatever comes out and ask them the other piece of this for us that I think can’t be understated is we’re a social animal and probably the best thing we can do to increase our vagal tone, improve our heart rate variability, drop our cytokines, is to connect with people. So safe social engagement is really important for people. If they’re afraid in their apartment, disconnected, they’re going to get worse. And unfortunately, when COVID first came out it was… What was the term, social …?

Dr. Dale Bredesen: Distancing.

Dr. David Clawson: Social isolation.

Dr. Dale Bredesen: Isolation, yeah.

Dr. David Clawson: But it’s really … Oh, social distancing. We can practice a form of physical distancing by staying a few feet apart, wearing a mask, which separates the spray and everything. But I don’t think we can afford to actually have social distancing. So whatever works to keep people connected, obviously if you’re with somebody and you can feel their presence with you, it’s a little harder over Zoom, even have some touch or something like that. It’s really important that we stay connected socially. And I think that we find with schizophrenia and Alzheimer’s, and despite all of our treatments, probably the best form of treatment is keeping people socially connected. And so that would be the one thing that I would really emphasize. We have this incredible ability to co-regulate each other when we’re together in a safe environment. So those would be the things I’d focus on.

Dr. Dale Bredesen: Okay. Thank you. Thanks, D.R. So then Cindy here says transkingdom communication is how we communicate at a cellular level and beyond. I think it’s a great point. And I think the research over the last 10, 15 years has just shown how incredibly important our various microbes interactions with us and really how they are part of us. The idea that we’re single individuals I think is long over. So absolutely trans kingdom communication, so critical. And then we’ve heard about this repeatedly and with multiple biomes and certainly it’s become part of medical practice, optimizing the oral microbiome and the gut microbiome and the sinus microbiome and all these sorts of things.

Dr. David Clawson: And I think being in safety allows for the environment for that good microbiome to grow as well. Whereas when we’re under threat, we’re phenotypically very different in it facilitates that pathogenic microbiome. So it’s bidirectional. We have to find safety to have a good microbiome and a good microbiome may push us into safety physiology.

Dr. Dale Bredesen: It’s a great point. And Cindy goes on to say it’s essentially that, basically when you’ve got appropriate soil, when you’ve got appropriate brain volumes, response is you’re getting more of a calm response to these attacking agents. So the microbiome, obviously, a huge part of that. And then Valerie says, “An aha moment. My friend nearly died with sepsis just over two years ago. It’s only been in the last months that her brain has become sharp again. It now makes sense.” And of course, this has been in the neurological literature for many years. People, especially people who have confusional states in the hospital are at very high risk for developing dementia within the ensuing 12 months. So this is a huge problem. And again, addressing this, getting to this threat and getting to the various –

Dr. David Clawson: And think about the things we do when somebody gets septic and particularly, shocky, right, with COVID. The protocol is to give them dexamethasone. Dexamethasone controls inflammation, but it’s highly catabolic. And it is really hard on the neocortex. So all these people who get COVID and get glucocorticosteroid have an amplified degenerative response in the hippocampus and the prefrontal cortex that they have to now recover from. And we do other things too. When we want to curl up in a ball in a shock syndrome, as a recovery strategy, we start pumping people full of adrenergics. This is a system that is exhausted. That’s why it’s curling up in a ball. And our response is to give them dopamine and norepinephrine to try to keep driving their heart rate when they really want to curl up in a ball.

And this is where diet gets really important. Your dog will curl up in a ball and become ketotic. And that stimulates part of the recovery and healing process because the ketone bodies turn off something nuclear, a factor B, that tells our genetic of code what to do in threat. And it turns that off and stops the production of the threat cytokines. So there’s things that we’re actually still doing in the hospital in shock syndromes that may be creating post shock syndromes thing.

Dr. Dale Bredesen: So then D.R., so what happens when you’ve got someone who’s a patient who’s having some cognitive decline? You are directing them to have less stress, less threat, but in fact, they have ongoing undiagnosed issues, pathogens, toxins, things that are actually normally created, in other words, appropriately creating. So what happens when you have a mismatch where you’ve got pathogens and inflammation, but you’re trying to convince the organism that it should be feeling safe, what happens then?

Dr. David Clawson: Well, those are the areas where I need help from functional medicine doctors and infectious disease docs to help rid the body of those. I can focus on the nutrition, sleep and appropriate exercise, not excessive exercise, particularly if they’re in a threat two falter faint physiology. You don’t want to of push that too hard. So I focus on those things and supplements where they’re indicated and making sure they have a safe home environment and getting them engaged to be psychologically more healthy because it’s the same soup. Your immune system can’t get rid of the pathogens if you’re in this threat physiology, because the immune inflammation may still be high, but your immune cells are relatively senescent in that phase. So I focus on this whole ladder and get psychological support, which is really hard to do now. There just aren’t enough people out there with the volume of mental health issues we have and then ask my colleagues to help me with the other piece of it.

Dr. Dale Bredesen: And then Valerie goes on to talk about generational trauma and healing. She says, “How do you suggest we shift from the amygdala to the frontal cortex for a reasoned control?” She said, “I had one person say if you can laugh in a difficult situation, it upshifts immediately as the brain can’t focus on both at once.” She went on to say to activate Broca’s area, we need to speak out something to be thankful. And this fits with her attitude of gratitude. What do you do when people are focused more on the amygdala and you want them to be focused more on the prefrontal cortex?

Dr. David Clawson: Wow. I think you’re beyond me on that one. I go back to all of those fundamentals, I haven’t really thought about that specifically, but I do think the expression of gratitude is very helpful as a social connection. I think gratitude starts at the cortical level to reformat the constructs that we’ve created, the negative narratives that we’ve created. But when I look at this the way I look at it as a ladder that we’re down in the soup all the way from the molecular level and the mitochondria and the cells and the nutrition and the sleep and the exercise and coming up through the autonomic nervous system and breath work, and monitoring heart rate variability, and then getting up a little higher into the brain, more into the emotional network, allowing free expression of emotions in a constructive manner.

And then from there, getting up to that cognitive behavioral reformatting and reconstructing our narratives, which I think we have to look at all of our narratives. We have so many false narratives and negative narratives that you can see that in our culture today. It’s just rampant. But I have this sense where I start with patients is always at the primitive physiologic level and work my way up. For me, the cognitive behavioral therapy is the cherry on top of the sundae.

Dr. Dale Bredesen: Interesting. And then we have here, Tim is talking a little bit about amyloid angiopathy which is interesting because we don’t really understand why it is that that males with E four, four tend to be at clearly higher risk for cerebral amyloid angiopathy and how much of this is related to cytokines and things like that. And then Valerie is asking about, and talking about, vagal tone and talking about family hugs, obviously something great for your vagal tone. She said first time in months. And again this is, I think, another part of the pandemic. There’s just been less interaction. There’s just been less travel, fewer hugs, those sorts of things, more fist bumps, and also the relationship with the GI tract. So these are all good. I think we’ll take the rest of them online. D.R., any parting thoughts before we move on and Julie, any parting thoughts for stress, Omicron, and the holidays?

Dr. David Clawson: I’ll let Julie do the Omicron. I want to plant a seed with people, and I may be off on this, but when I look, so I don’t come at this from the neuroscience background, as much as the rehab background and what’s the body trying to do and with ApoE4 or with ApoE, I go, “What does ApoE do?” It’s a lipid transporter, right? That’s what ApoE does. It moves lipids. And so what does beta amyloid do? Beta amyloid grabs lipids intracellular from the Golgi apparatus and transports it out of the cell. So ApoE, but ApoE4 can mobilize it, repurpose it someplace else, carry it off to another site. And so for me, I go this is part of this catabolic process of program deconstruction of certain cells in the body.

And so ApoE4 people, I would assume, were very good mobilizers with resources in prehistoric times. So that genetic pattern survived because it was a benefit to us, but chronic threat makes it a threat to us. And I also believe that what happens is when you’re done in your deconstruction process, so beta amyloid also brings fats into the cell, right? But if you’re done with your work, what do we do with proteins that are done with work? We phosphorylate them. We fold them up and they become dormant. So my concern with beta amyloid, we can make a similar argument for tau or alphas and nuclei entangles and bodies, is that those are actually phosphor related proteins that are no longer necessary. If we’re not building neocortical structures, we don’t need tau to be constructing axons or alphas to be constructing synapses.

So they get phosphorylated and they fold up. So my concern with those is they aren’t toxins at all that they’re actually metabolic, essentially, artifacts. And I often wonder if we give a signal of safety, whether we will then change their fossil relation pattern and they will open up and start reconstruction. I don’t know that, but I want to plant that seed with people that as long as we chase beta amyloid as a toxin, when it’s just a metabolic artifact, we’re never going to get anywhere in treating this disease. But if we start chasing metabolism and threat underpinning metabolism, we could make some great advances in treating the disease. So I’ll leave it at.

Dr. Dale Bredesen: And we know of course that the drugs that have reduced amyloid have not succeeded in improving people’s cognition who have Alzheimer’s disease. Julie, final thoughts for the holidays here?

Julie Gregory: I would like to leave everyone with some actionable information. And one thing that you and I have discovered Dale, is that taking regular deep breathing breaks throughout the day has raised our heart rate variability tremendously. But you don’t need a long period of time to shut your eyes, slowly inhale through the nose and even more slowly exhale. And just repeat that for a minute or two. And it’s amazing how that calms your autonomic nervous system. And it raises your heart rate variability. It’s accessible, it’s free. We can all do it.

Dr. Dale Bredesen: That’s a good point. And you know, Aida has been talking recently up about whether you the four, seven, one. What is the difference? So do you have a specific number that you for the inhalation, the holding and the exhalation?

Julie Gregory: For me, I’m not counting. It’s a long breathing in period and then twice as long, if not three times as long for the breathing out. And it just automatically calms my nervous system down. If I’m feeling anxious about something, my heart rate just drops immediately, just from a minute of that deep breathing.

Dr. Dale Bredesen: I find my heart rate variability jumps from 40 or 50 to 110 when I just do the breathings and it does and stay there forever, but it’s several minutes. It definitely impacts you to relax. And I’m realizing all the years, I didn’t do that, probably not the right thing. So I’ll leave it there. Hope everyone stays safe. Please be careful in these difficult times with Omicron and with all the stress for the holidays and all the pandemic issues. Just a tremendous honor to have Dr. Clawson here. And Julie, thanks to both of you and everyone, please everyone, have a great time with your families over the holidays.

Julie Gregory: Bye bye.

Dr. Dale Bredesen: Thank you. Thanks.