I am delighted to have Dr. Tommy Wood joining me today. He is an Assistant Professor of Pediatrics at the University of Washington, where he studies brain injury and how lifestyle choices and environmental factors impact brain health, cognitive function, and chronic disease.
In today's discussion, we explore age-related cognitive changes and how cognitive function peaks early in life and evolves through retirement. We cover specialization versus lifelong learning, the role of memory, the effects of childhood trauma, and the physiology of dementia and Alzheimer's. We also discuss how sleep impacts brain health, lifestyle factors, labs to consider, including homocysteine and Omega-3 levels, and the value of skeletal muscle mass in preventing dementia. Dr. Wood also shares his insights on concussions, traumatic brain injuries, and supplements like creatine and sex hormones for maintaining cognitive health.
This conversation with Dr. Tommy Wood is exceptionally insightful, and I look forward to having him back on the show again.
IN THIS EPISODE YOU WILL LEARN:
Common cognitive changes that occur in perimenopause, menopause, and beyond
How some aspects of cognitive function remain relatively stable or even improve with age
Why education is not necessary for cognitive development, and how specialized careers can reduce cognitive stimulation.
How retirement impacts cognitive function
The benefits of physical activity, particularly cardiovascular fitness, for brain health
Why memory issues are not necessarily indicative of dementia
How trauma can lead to smaller brain volume
Why regular sleep and proper circadian alignment are crucial for maintaining brain health and cognitive function
Blood markers for cognitive health
Why muscle mass is essential for overall health and cognitive function
“In general, across the population, there is a fairly linear decrease in most cognitive functions from about the mid-20s.”
-Dr. Tommy Wood
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Connect with Dr. Tommy Wood
Transcript:
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the honor of connecting with Dr. Tommy Wood. He is an Assistant Professor of Pediatrics at the University of Washington, where he studies brain injury and how lifestyle choices and environmental factors contribute to brain health, cognitive function and chronic disease. Today, we spoke at length about age-related cognitive changes in function and memory, where our cognitive function peaks in our early life and significant changes in retirement, the role of specialization versus ongoing learning, open skills, activities and benefits, the role of memory, the impact of adverse childhood events and trauma, the physiology of dementia and Alzheimer's, the impact of sleep on brain health as well as other lifestyle measures. key labs to look at, including things like homocysteine and Omega-3 status, the value of skeletal muscle mass and prevention of dementia, the impact of concussions and traumatic brain injuries, as well as current relevant research, the role of supplements for neurocognitive health including creatine. And lastly, the role of sex hormones and cognitive changes and decline in middle age and beyond. This is an invaluable conversation, probably one of my favorites I have recorded all year and I will be definitely having Dr. Wood back.
[00:01:51] Well, Dr. Wood, such a pleasure to have you on the podcast. I've been really looking forward to this conversation.
Dr. Tommy Wood: [00:01:56] Thanks so much for having me. It's a pleasure to be here with you.
Cynthia Thurlow: [00:01:59] Yeah. I would really love to kind of initiate the conversation around, based on your research and interactions with individuals that are going through the aging process. So women in particular, perimenopause and menopause, let's talk about some of the cognitive changes that are common to see in this age group and beyond.
Dr. Tommy Wood: [00:02:21] So when you think about the changes in cognition across the lifespan in aging, I often try and start a little earlier. A lot of my work is actually in developing brain as well. And we know that as we initially get older and we are in school and we get into our 20s, that's when we really start to develop a sort of baseline of cognitive function. And then depending on what aspects of cognitive function you're measuring, there seems to be on average across the population, and I think this is modifiable and hopefully that's a lot of what we'll talk about today. But in general, across the population, there's then a fairly linear decrease in most cognitive functions from about the mid-20s.
[00:03:01] And this can be broken down into different aspects of memory, short-term, long-term memory, parts of executive function, complex decision making. But there are some things that do remain relatively stable. So aspects of crystallized intelligence, so how we understand the world and integrate information, that's something that we remain relatively stable or we even get better at over time. There's kind of like a fancy word for wisdom, right? We become better at integrating information and thinking about the world around us in a more holistic manner. As you get into your mid to late 40s to 60s, in that kind of area, the average decline remains relatively stable.
[00:03:44] Often we think that perimenopause and menopause is just going to be associated with this sudden change in how we think and feel, but that's not guaranteed and that definitely doesn't have to happen. But we do know that different sex hormones are critical to brain health and function. So as those change and some of the hormones that regulate those, there's now a lot of data that suggests that FSH, which is one of the master hormones that regulates estrogen and progesterone and that goes up during menopause, and then that may affect cognitive function as well and there's a whole bunch of research in that area. So there's definitely, in general, people report changes in sleep, which then affects cognitive function, but also certain aspects of memory in particular, there can be a slight drop during that period.
[00: 04:33] The reason why I'm hedging many of the things I say is because I think there's two parts to this. One is, yes, absolutely, there are biological changes that happen, and they can affect cognition, and they do. And I think there are ways that we can address that. But part of what also happens is we tell ourselves this story that there’s going to be this decrease in how our brains function, and you’re not sleeping as well, and that’s going to affect how the brain functions. And I think most of this or a lot of this is, again, this story that society has told us that you’re just going to get worse over time and especially during menopause. But that doesn’t have to be the case.
[00:05:09] And part of it starts with acknowledging that some of it is due to our own expectation. I think if we acknowledge that, then there are certainly a number of things that can be done to address some aspects of cognition based on lifestyle and maybe hormone replacement therapy, if relevant. But equally, some of it has to start with just not expecting a decline when there doesn't have to be one.
Cynthia Thurlow: [00:05:35] Well, I love the reframe, which I think is so important, the self-fulfilling prophecy. If we presume this is going to happen, that's probably logically what will happen. And getting back to the baseline cognitive function where our peak is, I think about, I have teenagers and young adults. I have a college age kiddo, and a teenager. And is it because in that span of time, we're still in formal education, formal schooling, is that what is helping to drive the kind of peak cognitive changes? And then when we're out, “In the real world, that's when we start seeing a decline if we're not actively working against it.”
Dr. Tommy Wood: [00:06:15] Yes, essentially. But it doesn't have to be driven by a formal education system. It's just that up until whenever we leave formal education, and which is about the time that cognitive function, “peaks.” And so those who spend longer in formal education generally the greater their peak of cognitive function, although that doesn't necessarily change the rate of decline afterwards. It's essentially that up until that point, all you're doing, like your job is to learn. So your job is to drive plastic mechanisms in the brain that create these systems that allow for these cognitive processes to occur. So, yes, the formal education system is very good at doing that, but it doesn't have to be due to that.
[00:07:00] So if I say this and somebody's listening to this and their kid is in like, forest school or their homeschooling or whatever, all of that stuff's great. It's not that it has to be bums on seats in the local public school. It's just that it's this process of learning and engaging with the environment and new material skill development. That's what seems to drive these aspects of cognitive function. So that then applies later in life as well. And you're right, what I think happens is when we leave formal education, we go into the workforce and we tend to do two things. One is that we specialize, and if you're a surgeon, I want you to specialize, of course, I want you to do the same thing again and again and again and again. But that process then doesn't keep providing this ongoing learning and skill development that is critical to maintaining cognitive function.
[00:07:58] So we then just have to find that elsewhere. But that's not what most people do, because either people are busy and stressed. But also, one thing that happens when you transition from childhood into adulthood is that you stop doing things that you're bad at because we don't like being bad at things. But it's that process of failure and learning that really seems to drive a lot of these processes. So I think some of it, and of course, some of this is related to aging processes that we still can't fully stop, of course, aging is inevitable still. But a big part of it is societally driven that we are not continuing to engage in learning processes as we get older. And so that, I think, is a big modifiable part of then what might change how our cognitive function works later in life.
Cynthia Thurlow: [00:08:49] It's so interesting because as an allopathic trained clinician, as a nurse practitioner, I spent 16 years in cardiology. And specialties are very siloed for a reason. That's kind of the American medical model at this point in time. But I got to a point where I was no longer learning. I remember my -- this was eight years ago, my job kept offering me a better schedule, no holidays, no this. And I said, “But you just don't understand, I'm no longer learning.”
Dr. Tommy Wood: [00:09:16] Yeah.
Cynthia Thurlow: [00:09:16] And so that you are speaking to that, we as human beings, as organisms, we are designed to be lifelong learners. Whether people ascribe to that philosophy or not, I think that the failure and learning process on the other side of that, I certainly tripped and fell on my face a couple times as an entrepreneur, but so much sweeter because you're learning new ways of adapting to your environment. Strategies I used in medicine don't always translate over into how my life is now, but it’s certainly provided tremendous intellectual stimulation. And I think I would imagine that individuals that when they retire, I think about my parents in retirement as an example, there’s a change in that cognitive demand because they’re maybe not in a super stressful environment.
[00:10:04] My mom retired from a very stressful job that she loved. That removal of stimulus probably then leads to some degree of cognitive decline. Let’s just speak to that population, how do retirees, and I would imagine this is where you see people that go on and they get another degree, or they’re a learning pickleball, or they’re doing Sudoku like my mother-in-law does. What are the things that people can do to continue to stimulate their brain beyond sitting in front of Netflix and binging?
Dr. Tommy Wood: [00:10:33] Everything that you said certainly seems to be true based on the research that we have available. So still, during the work period, there was a recent study that came out of Norway that looked at the degree of intellectual stimulation that came from a job and then later dementia risk. And what they found was that the more repetitive and less varied and less intellectually stimulating your job was, the greater your risk of later dementia. I think that's essentially, what's your rate of decline? You're going to have a decline in cognitive function. We can't completely eliminate it, but if you manage to slow that decline enough, you never reach the point where you have a significant loss of cognitive function before you essentially die of something else for want of a better way of phrasing it.
[00:11:18] What made those jobs more varied was, are you problem solving? Are you learning new skills? Do you have to do something different every day? I think depending on your job, you can either get it from your job or you can get it from outside of your job. And then this relates to essentially the entire lifespan that we might talk about. So learning new complex skills is, and ideally in a social environment, because we know that social connection is critically important as well that's essentially where the magic happens. So this could be like, pickleball is a great example. A lot of the papers that I write in this area, I have a podcast with a neurologist, Dr. Josh Turknett, and he plays pickleball. He's a big pickleball fan. And so it could be pickleball, it could be learning a new musical instrument, any other kind of complex sport, ideally something that has some kind of motor component and reacting to the environment.
[00:12:11] In the research, they call these open skill sports. But languages, music, dancing, any of those kind of activities, I think all of them fit this pattern. Then you can certainly layer on top things like volunteering or other ways to donate your time or go out into the community and interact with others, because just that process of building social relationships, the benefits of contributing to something outside of yourself, those seem to play an additional benefit on top of the important parts of continuing to learn and develop new skills.
Cynthia Thurlow: [00:12:43] And what is it about pickleball? I know that it's having a moment. What is it about pickleball that is particularly beneficial for cognitive function? I know the answer to this, but I think it would be really interesting for listeners to understand. Like I jokingly tell my husband, “We're both now in our 50s.” I'm like, “We have to learn how to do pickleball because it's so important.” But let's speak to pickleball as one example of these open skilled activities that can be helpful.
Dr. Tommy Wood: [00:13:11] So whenever I think about something in terms of the way that it might contribute to cognitive function. I have a framework in my head that is essentially three parts that interact and rely one another. So the first part is cognitive demand, like, “How are you challenging the brain itself?” Then the next part, something that I call supply, which essentially is, “Do you have a healthy vascular system that’s sending oxygen and nutrients to the brain? And then also do you have enough of the nutrients that the brain requires in order to function?” And then you have support, which is essentially things like sleep and recovery, but also preventing chronic stress, inflammation, toxic exposure, some of these things that can inhibit the brain from adapting and performing at its best. So, pickleball, where you have a cognitive demand, right.
[00:13:59] You're constantly having to react to and interact with the environment, which in itself is challenging the brain. Plus, there's going to be some aspect of skill development. The more you play it, hopefully the better you get to up to a point, then you're going to be improving your cardiovascular fitness so you've improved some of the supply side. And we know that cardiovascular fitness is one of the most critical determinants of long-term brain health. Some people say that what's good for the heart is good for the brain, and generally that seems to be the case. And then we know that if you do some kind of physical activity, generally you sleep better that night. So that's going to support all these processes. There's hopefully a social component, as long as there's not too much animosity against the people on the other side of the net. So then there's some of those effects on stress and those kinds of things come to play. So pickleball could essentially fit into all of those buckets in one way or another.
Cynthia Thurlow: [00:14:49] Yeah, I love that because I think that stimulation, both physical, intellectual, mental, spatial, is key to ensuring that you're not getting static. I think it's so easy, and I say this in the most loving way possible. But what I see in a lot of individuals, not just patients or even family members, it's that some people, as an example, they'll retire and then they kind of slow down. They're not as socially, they're not interacting with peers or colleagues. They are not as physically active maybe they're the doing more sedentary activities. I think there's a time and a place for Netflix or Hulu when I don't denigrate them. But that's a passive interaction with a stimulus, as opposed to some of these other things that you've touched on. And where does the concept of memory come into play with cognitive changes as we're getting older?
Dr. Tommy Wood: [00:15:43] I never quite answered your question about retirement. And the evidence that exists across multiple different populations suggests that the point at which the decline in cognitive function is the greatest is actually at retirement for all of the reasons that you listed or at least that's what people think. That's even after you take into account say, medical conditions that maybe would have caused you to retire earlier. Even once you take that into account, you're right people tend to withdraw from engaging activities on multiple fronts, and that probably accelerates some of the decline. So, when it comes to memory changes, there's a few things that I think are interesting and worth considering.
[00:16:23] One is that, yes, the structures in the brain that we know are critical for memory, like the hippocampus, they do tend to decrease with size as we age and the function decreases. This occurs regardless of whether you then go on to experience dementia. But the hippocampus in particular, is particularly late on in something like Alzheimer's disease is particularly susceptible to that process. But it is we think, at least partly reversed, particularly with things like physical activity. And there's a few studies in humans that show that you can at least slow the decline, if not increase or support the structure of the hippocampus as people get into their 70s and older. So that's one part of it, that there is this process that occurs over time, and it is at least partially modifiable.
[00:17:13] The other part of it is that we're often assuming that any time we can't remember something, that something pathological is happening, you don't remember where your keys are, and then all of a sudden, you're like, “Oh, my God, Alzheimer's is coming.” And again, I think there's some reframing of expectation that's important. There's a few parts of this, but one is that as you get older and you've developed more memories, and when you have discussions with the real experts in memory, whether we think about memory like a hard drive or not, because it's not really, but it allows us to at least have some way to discuss it. Imagine that there were just more files in your hard drive, right? Because you've experienced more things, and your folder of places where I've put my keys is really full. So particularly because where you put your keys in the grand scheme of things, isn't very important.
[00:18:18] The brain just doesn't assign as much importance to it, and either doesn't encode it in the first place, because you haven't said this is really important, which requires focused attention to remember something. Or if you put them in a different place every time and you've got hundreds of different files to retrieve from, that process just takes longer, which is completely normal. That doesn't have to be some pathological thing. Which kind of brings us to the point that if you do want to remember something, there are ways to do that, and it does really require focused attention. Rather than just like, you drop your keys and then you expect your brain to remember, it's constantly filtering out stuff that you don't remember, which is also very important.
[00:18:59] And so part of it is, “Did you even tell your brain that you wanted it to remember where your keys are?” Then the other part of it is, there are some things that just happen in day-to-day life that affect memory, and they're very common, and we don't necessarily need to be super concerned about them as long as we address them, ideally somewhat longer term. So those two main things or three things that affect our ability to retrieve information, how well we're sleeping. And this is not like, “Did you have one night of bad sleep?” I think we've gone a little bit too worried about that, particularly with all the sleep trackers and stuff like that. But long term, this is important. Then your overall stress burden also affects retrieval, as does just like your total cognitive load. If you're trying to do eight different things at the same time, whether you can remember where you put your keys goes way down on that list.
[00:19:53] When we think about what's actually problematic, it's lack of encoding. So there are three parts of memory broadly, you can get much more technical than this. So again, any memory experts, like, [00:20:07 [unintelligible]. But there are three main things to think about. One is encoding, like, “Did this information go into your brain and you try and write it?” The second is consolidation. So is that memory then stored somewhere that you can get it later? And then the last is retrieval, “Are you able to access that memory and bring it back to the front of your mind?” So for most people either they didn't encode the information, but it's because they just didn't really focus on trying to do that. But for most people, it's generally a problem with retrieval, which is more to do with, are you sleeping? What's your cognitive load, what's your stress level? And all of those things you can change if you want to if you're able to.
[00:20:47] And then when we think about dementia, so for Alzheimer's disease, then the problem is encoding. It's like even if you tried really hard to get that information into the brain, like your brain didn't even try to write it into memory and that's the problem that we see in actual disorders of brain function. But it's much less common for most people who are experiencing some memory issues. The former thing is more likely to be the case. So if it's just like that thing that's like, it's on the tip of my tongue, like it's right there, that's a retrieval issue. And it's more likely to be these other factors that hopefully you can modify now and have some control over, rather than some pathological process that maybe at this stage at least we have less control over.
Cynthia Thurlow: [00:21:29] Well, it's certainly reassuring, because I think that for many people, they automatically think the worst-case scenario, like, “Oh, I forgot where I put my keys or I forgot where I parked.” Therefore, this must be early-stage dementia. And that’s certainly not the message that you’re sharing. I did want to ask about the hippocampus, so it has a special role with consolidation of memories. What about individuals that have experienced adverse childhood events? I know you mentioned a lot of your research was in younger populations and how it can, I don’t want to use the word damage, negatively impact the hippocampus long term. Are you familiarized with any research around this? I guess the more I understand about adverse childhood events, the more interested I become in fully understanding the net impact on brain health long term.
Dr. Tommy Wood: [00:22:15] Yeah. There are multiple things that play a role here. One is that we know that adverse childhood experiences and potentially even adverse experiences that happened in utero or before are then related to smaller total brain volumes, essentially across the entire brain, but particularly some area like the hippocampus. You’re starting with a smaller structure to begin with that maybe functions less well. And then it’s not just the volume of a structure, but we know that trauma can change inflammatory and stress reactivity patterns that we also know then affect long-term brain function. So there’s the number of mechanisms by which trauma, particularly childhood trauma, but potentially trauma at any age, and that could be both physical and psychological, then affects long-term cognitive function.
[00:23:07] The potential problem when we talk about it is very important to talk about, but what I don't want people to think is that this happened to me, therefore this is going to happen to me in the future. Now, of course, if a significant history of trauma is going to require a lot of expert input and therapy and potentially medications if they're indicated. There's a lot that can and should be done. But even in, after starting in suboptimal circumstances, the brain has massive capacity for repair and plasticity. It's not directly related to trauma. But one of my favorite studies in this area looked at the brains and then cognitive development of kids who are born preterm. So, which is a big area of my research. We know that the more preterm you're born, the greater the likelihood that you'll have some kind of neurodevelopmental impairment later in life.
[00:24:06] So in this study, what they did is they looked at the brains of babies born preterm, and they looked at whether there was any evidence of injury before they left the hospital. And in general, you stay in hospital up until approximately the date that you would sort of like term when you were projected to have been born, if you were born a term. So if you're born extremely preterm, which is less than 28 weeks, you'll spend three months in hospital before you get to that kind of age approximately. They then looked at cognitive function into early childhood and what they found was that greatest effect on later cognitive function, regardless of whether you had injury in hospital as a baby, was the environment that you went home to. So the environment that can have a massive effect on the brain, even if it starts with significant injury.
[00:24:55] I think we can call psychological trauma, a type of injury to the brain. If we think about all the different things that can be done to improve cognitive and improve and support cognitive function. So if we're worried about inflammation in certain parts of the brain or we're worried about stress responses, and stress affects things like blood sugar control, which we know is really important for the brain, all of these things are things that we can potentially modify. So even if the beginnings of life were suboptimal, I want people to know that everything suggests that is not like, “Sign your ticket for some later cognitive problems.” So, yes, they’re very important. They should be dealt with because they’re very serious. But I think there should still be hope that these things can be changed over time.
Cynthia Thurlow: [00:25:44] Thank you. I think that’s such an important message. You’re weaving this into the conversation over and over again. But for people to know biology, per se, is not your destiny. If you’ve grown up, whether it's preterm delivery or grew up in a home where there was a lot of physical or emotional abuse, it does not per se indicate that that is your destiny. I think that's an important distinction to make. A lot of questions came in around neuropathology. Everyone in middle age, that is experiencing changes in the way they process information. And this goes for men as well. It's not just women. Help us understand key differentiators when we're looking at dementia, because not all dementia equals Alzheimer's. On a spectrum, that is the most severe manifestation of neurocognitive decline. Help us understand kind of some of the basics and differentiators.
Dr. Tommy Wood: [00:26:40] When we talk about dementia, most people think about Alzheimer's disease, which is one form of dementia and is the most common form of dementia. There are other forms of dementia, and maybe we just start by defining dementia. Dementia is essentially the loss of cognitive function, such that you get to a threshold where you're essentially no longer able to safely perform the routine activities of just looking after yourself every day. There are other forms of dementia that there's a vascular dementia. It's associated with problems in blood flow to the brain, and lots of mini strokes is part of that pathology. But there's a big overlap between vascular dementia and Alzheimer's disease, because I already said that we know that how healthy your vascular system is and important for Alzheimer's disease as well. So those often overlap.
[00:27:33] But then there's dementia associated with things like Parkinson's disease and a number of other more or rarer neurodegenerative conditions. In terms of the trajectory then, yes, I don't think Alzheimer's is the most severe dementia, but it's once you get to like the end stages of cognitive decline. If we think about this continuous trajectory downwards, before you get to frank Alzheimer's disease or dementia, there has to be some progressive loss of cognitive function. So first you get into something that we call mild cognitive impairment, and that's, again, you would diagnose on some kind of memory test. And then before that, there's a lot of research and interest into, well, what's the trajectory over time, right? Because even before you get to mild cognitive impairment, you've probably lost some cognitive function. So what's the trajectory down into that region, and how long does that take? And it's probably over decades we talked to this slow decline that everybody will see on average and some people will have a more rapid decline and they'll end up in MCI, mild cognitive impairment or dementia.
[00:28:40] And then there's also interesting-- “Well, what's happening in the brain while this happens?” So you mentioned neuropathology. So right now, this varies, at least in general consensus is the very strong connection between the buildup of pathology in the brain. So this is different proteins, amyloid plaques, tau tangles, hyperphosphorylated tau. There's a connection between these and dementia and cognitive decline. If you really look at the data, the connection isn’t that strong. It’s not like if you have a lot of amyloids, you’re going to get Alzheimer’s disease or vice versa, because there are a ton of exceptions where people-- you look at their brain and you’d be like, this person has Alzheimer’s disease, and they actually functioned just fine. Or you might look at somebody’s brain and say, “This brain looks okay, and this person was diagnosed with dementia.” So there’s a loose link between this pathology that’s accumulating in the brain and neurodegeneration and dementia symptoms.
[00:29:39] So explaining why people do and don't then get dementia in these different contexts is sort of like the next phase of the research that's being done. There are some blood tests that seem to be, you're able to pick up some of this early on. So right now the best candidate is something called pTau217, which people can get access to. But again, it's not perfect, and I don't think it's as good a predictor as assessing somebody's nutritional status, their cardiovascular fitness, their sleep, all these other things. But generally, those things don't make it into the sort of the fancy medical studies because everybody's like, “Oh, yeah, we know this is important, and then they don't do anything about it.” [Cynthia laughs] But so even if we accepted that things like amyloid and tau are the primary drivers of dementia, there's now, because of these exceptions, where the pathology burden doesn't match the cognitive function, there are these ideas of resilience and cognitive reserve, which basically says, “How well are you able tolerate a large burden of pathology or a large amount of stress or sleep deprivation, and still have good cognitive function or not experience dementia?”
[00:30:52] So we don't actually have to resolve whether the pathology is the problem or not because we can say, “Well, what are the things that contribute to reserve and resilience?” All of those things are based in lifestyle. Some of it's going to be genetic, but there's not much you can do about that. So significant contributors to reserve and resilience are physical activity, cognitive activity, nutritional status certainly plays a significant role. All of those factors, regardless of what else is happening, regardless of any pathology that's accumulating in your brain that is difficult to measure and interpret, we can then step back and say, “Well, regardless of that, we know that there are these important lifestyle factors that are going to play a significant role, and then that’s something that we can actually change.”
Cynthia Thurlow: [00:31:39] I think that’s really significant because I’m sure there are many people listening who are thinking whether they are genetically more susceptible to some neurocognitive decline or perhaps they can control only so many things, recognizing how important lifestyle is. And it's interesting when I think back to many years ago, learning about the brain and the glymphatic system and the role of sleep and why deep sleep is so important, it's reassuring to know that you can have a burden of these tau proteins and amyloid in the brain that doesn't vis-a-vis indicate that there's a direct connection with, “Oh, you're going to have neurocognitive decline.” So there has to be more to it than my cursory understanding from years ago when we’re learning about brain physiology and you mentioned multiple times how important sleep is. So could we speak to what it is about sleep itself beyond the glymphatic system that is so brain protective, brain important?
Dr. Tommy Wood: [00:32:40] So this is probably two or three main parts to this. One does, we think involve the glymphatic system and that's still partly a debated topic currently. The original studies that essentially discovered the glymphatic system, now, more than 10 years ago, what they showed was that during sleep, there's this expansion of the fluid volume around the brain as the sort of the solid structure of the brain shrinks. And then that allows for more fluid to essentially travel along the out. So the glymphatic system kind of runs on the outside of the blood vessels through the brain and kind of drives some of this clean out process for want of better words. So you're essentially able to wash out accumulated and some of it-- So they've showed that the glymphatic system clears out oligomers of amyloid and maybe other things like adenosine and things that drive sleep need. So it's essentially like you're just washing out the brain while you sleep.
[00:33:41] The reason why I say it's debated is because there was a recent paper that suggested that actually sleep isn't the primary driver of this and maybe it's something else. And so the experts are kind of debating this topic. There was actually a super recent study that only looked at one person, in one guy, they imaged his brain like dozens of times. What they showed is that brain volume. So, like the solid version of the brain versus fluid part of the brain has a circadian rhythm. And so as you sort of get towards the evening, the brain starts to shrink and glymphatic and fluid systems start to expand. So it may not be primarily driven by sleep, it may be driven by circadian rhythm, which could then help-- If that's true, generally rather than just like one guy, then that could help to, I think, reconcile some of those issues that essentially says that as you transition towards sleep, your brain starts to prepare itself for this clean out process, which is driven by circadian biology. But then that also means that we need a strong circadian rhythm in order for that to happen. And of course, sleep is a key component of that.
[00:34:43] Other aspects of sleep are more related to this just being the period that. So, we just talked about what's happening outside the solid structure of the brain, but within neurons and other cells within the brain, when we've particularly driven some kind of stressful, demanding process, and I mean stress in a good way, right. We've kind of challenged those regions. We know that if you work one part of the body say, physically, the associated part of the motor cortex that ran that bit of movement, then has a greater sleep drive and sleep need that night. So these things are directly connected. If you're going to challenge a part of the brain, then the recovery and plasticity process requires sleep. So those are like the two main components. There's sort of the metabolic clear out, but then there's also the more direct on the level of each cell, particularly if you've driven a certain amount of cognitive challenge, then it's going to need that. That's when you rest and recover and repair. Whenever I talk about challenge in the brain, I usually link it to exercise because people can understand that a little bit more. And as any gym bro knows, you don't get bigger in the gym, you get bigger when you're recovering and sleeping afterwards. And so the brain is essentially the same.
Cynthia Thurlow: [00:36:00] It's so interesting. I'm down a nerdy rabbit hole writing my second book, talking about circadian clocks specific to the gut microbiome, but relevant to the brain because of that bidirectional relationship. So that is so interesting and it reaffirms why, when you have a day where you're very physically active or more intense exercise, you tend to sleep more restfully. Provided that you haven't overdone it, that makes a great deal of sense. When it comes to lab work that is looking at either marker for prevention of cognitive decline. I'm thinking specifically about like homocysteine or apoE. I know that a lot of people are in full panic mode because they have the less desirable genetic variant of apoE. What are things that you'd like to help educate people around, like things that they can tangibly talk to their healthcare provider about, that they can look at as examples of things that can either identify they're more susceptible to neurocognitive decline or well really, that’s what I’m thinking about, especially as it pertains to homocysteine.
Dr. Tommy Wood: [00:37:07] So I think something that everybody can and should do is assess baseline aspects of nutritional status and overall health through some basic blood work. Then we’re talking about you do a CBC with differential we know that iron status is really important for the brain. We know that vitamin D is really important, magnesium status is important. We know that B vitamin status is critical. So there homocysteine is a really important market, not only because it kind of tells us a little bit about one carbon metabolism, methylation, as well as requirements for things like riboflavin, B6, folate, B12. But there's also some evidence that homocysteine itself can directly, particularly accelerate the phosphorylation of tau. So it could be like a marker of some nutritional status issue, but also may itself be directly pathological.
[00:38:02] We know that homocysteine status and Omega-3 status interact from several clinical trials now. So if you have elevated homocysteine and you like supplement with Omega-3s, those Omega-3s don't have an effect unless you have lower homocysteine or you actively lower homocysteine with B vitamins and vice versa. And so often people will go out and you'll look at all the literature on Omega-3s for decreasing cognitive decline, dementia, and they’ll say, “Oh, it doesn’t work.” And that’s because they never checked homocysteine. They never looked at these other factors, these individual things that you can fix on their own. You have to think about the whole system. And when we think about the structure of the membranes of the brain, you need the methylation system working to get your Omega-3s into your brain where you want them to be. It makes sense why they would interact.
[00:38:52] So those basic nutritional markers are important. Then we mentioned cardiovascular health. So lipid status I think is important. Blood sugar regulation, so prediabetes and diabetes are significant risk factors for cognitive decline in dementia. So just those basics, I think, can really get you a long way. Then, when you think about other risk markers. Obviously, apoE status is the most influential single polymorphism in terms of risk of dementia, but there are a number of different ways that this can play out. So there have been studies where they’ve had people test their apoE status, and some proportion of them, like 25% to a third said, “I wish I never knew.” Because all it did was increase their stress around the fact that they think they’re more likely to get dementia. And I would argue the stress has more of an effect than the apoE status does itself. There are also multiple studies in multiple populations that suggest that ApoE4 is not what we would call fully penetrant. It's not directly or unchangeably related to risk of dementia to put it that way.
[00:40:02] So these tend to be sort of indigenous or hunter-gatherer groups. The Bolivian Tsimane, there was a study indigenous Americans, there was a study in the Nigerian Yoruba. And in those groups, ApoE4 status isn't really related to dementia risk at all. And that could either be other aspects of genetic background, or what I think is more likely is that ApoE4 exacerbates other environmental risk factors on dementia risk. And there is one study that suggests this. Looking at Sicilian Italians who, if they’re living at home in Sicily, their ApoE4 status doesn’t increase their dementia risk very much, but as soon as they move to America, essentially with the same genetic background, they have an increased risk of dementia, their ApoE4 carriers.
[00:40:51] There are other studies that then suggest just like this, that if you have ApoE4 essentially makes other dementia risk factors worse. So lack of physical activity, poor quality diet. In those settings, ApoE4 has more of an effect. So because most of the research on ApoE4 is done in the US or most of Europe, where health in general has gotten worse over the last few decades, then in that setting, ApoE4 does look like a risk factor. But if you remove those environmental factors, you can probably mitigate, most of if not all of, the additional risk that comes from being a carrier of ApoE4.
Cynthia Thurlow: [00:41:34] That really makes a great deal of sense as it pertains to Omega-3 status are we looking at consumption of fish? Are we looking at supplementation? When you’re looking at the research, what appears to be the greatest-- which is one superior to the other, is what I’m trying to ask, because inevitably, this is what happens people don’t like eating certain kinds of fish, they don’t want to eat the fatty fish. Therefore, they’ll take the supplement. And so we kind of go back and forth. I have a 17-year-old who hates salmon like hates it with a passion. So whenever we eat it's the only time I'll make him something else. But understanding the role of Omega-3 is especially DHA. Where does the research suggest, is it nutrition is superior to supplementation? What are your thoughts there?
Dr. Tommy Wood: [00:42:22] Most of the epidemiological data, so it's not like randomized controlled trials, but most of those data suggest that seafood consumption is better than taking a supplement. And this is because, fish doesn't include just Omega-3s, right? There's selenium, there's a whole bunch of other micronutrients. If you do eat salmon, then you're thinking about some of the pigments, astaxanthin, some of these things that can also contribute to brain health. So I think if I had to pick one, I would pick seafood. However, when you do the randomized controlled trials, then they generally use a supplement. I don't know of any randomized controlled trial that randomize people to salmon or not. Maybe that exists, but when you look at some of the supplement studies, so like, there was the Omega AD trial where they supplemented with long-chain Omega-3 fatty acids, and then this was one of those studies where they saw that it was only benefit in those that had low homocysteine. There wasn't benefit in those that had higher homocysteine. That was one of the studies that contributed to this idea of an interaction.
[00:43:26] But we also know that supplementing with Omega-3s can improve things like cardiovascular disease risk. So if you're decreasing triglycerides, you're decreasing risk of atherosclerosis, even if it's indirect, you can be having benefits to the brain. And if you are consuming some DHA as a supplement in particular, and you have a reasonable B vitamin status, that DHA should still end up doing what it's supposed to do in the brain. So I think the benefit is greater from seafood, probably because of other things that are also in seafood. But that doesn't mean that supplements won't beneficial as long as it-- again, then we'll return to high quality supplements making sure that these other things line up as well.
Cynthia Thurlow: [00:44:10] Is there value in doing some of these Omega-3 blood tests, like Omega-3 Index, Omega check? I mean, I'm sure there are listeners listening that are wondering if their levels are where they should be, are they therapeutic? Do they need to worry? Are we getting too nuanced in this questioning? But I know my listeners will be asking me the question, so I'm going to ask the expert.
Dr. Tommy Wood: [00:44:33] Yeah. So I'll declare upfront that Bill Harris, who is the founder of OmegaQuant, is a friend of mine and colleague. But I do think that the research is good enough to suggest that if you're uncertain, particularly if you're supplementing it, if you don't know if you need a supplement, you don't know if you need to increase your seafood intake, then something like the OmegaQuant or, it doesn't have to be that test, any other test that assesses Omega-3 status I think is important. As long as you put it in the context of all these other things, it's not the one thing that you should focus on. But if you're able to get access to a good basic blood test that covers a range of nutritional markers including Omega-3 status, then I think that gives you a good starting point to decide, “Do I need to change something or not?”
Cynthia Thurlow: [00:45:17] I think that's certainly reasonable. And how does the importance and everyone in this podcast knows how important skeletal muscle mass is. How does skeletal muscle mass fit into prevention for dementia? I think it's not just aesthetics. There's so much more to it.
Dr. Tommy Wood: [00:45:36] Just last week I gave Ignite Talks, which is these, like short, like five-minute TED style talks on the importance of muscle mass for brain health.
Cynthia Thurlow: [00:45:44] I didn't know that. See, it was serendipitous.
Dr. Tommy Wood: [00:45:46] [laughs] Yeah. I think that it does play a big role and for a few reasons. One is that muscle mass is partly an indicator of overall health, as well as how you're interacting with the environment. Because interacting with the environment, we know is important for the brain, and doing so requires a certain amount of muscle mass. So some of the relationship is probably reverse causality. As your brain function declines, if withdrawal from society, you're doing less, then muscle mass is going to decrease with that. However, there are several studies that show that if you put somebody on a resistance training program, you're now like in their 70s and older, and you're just like something super basic twice a week, six different exercises, three sets of eight. Just like the most standard resistance training, could be machines in your local Planet Fitness, buy it doesn't need to be more complex than that.
[00:46:44] You see significant improvements in brain structure, particularly in the white matter, and you see significant improvements in cognitive function. Then you think about, “Why that might be the case.” We now know that muscles are organs, right? They secrete factors into the blood myokines that go around and affect a whole bunch of things like decrease inflammation. We know that when you move your muscles, you improve blood sugar control. We know blood sugar control is critical. Then we already talked about sleep and all these other factors. So actually, moving your muscles then essentially affects systemic health, including the brain both directly and indirectly. So we've done some studies looking at some data like this. We published a paper a couple of years ago where we looked at muscle mass and muscle strength, and we use the dataset where they had leg strength, because that, I think, is one of the most critical measures. But it's quite rare because people just, like, normally look at something like grip strength. Grip strength is okay, but I think leg strength is a better measure.
[00:47:43] And actually, what we found was that strength, especially strength relative to your body size, was the best predictor. So it's not just that more muscle is better. It's generally that you're training and building strength relative to your body size. So if you're bigger, you maybe need to be a bit stronger, but those things do tend to go together. In general, if you train your muscles, they get both bigger and stronger at the same time. So those things kind of come together. So then you can think about body weight exercises, improving your ability to move your body in space against resistance, pull-ups, squats, push-ups, and all of these things can be progressed from like no ability all the way up to extreme calisthenics if you wish to. But I think that's really the focus, just trying to build strength. And at the same time, you'll increase muscle and then you'll get all those benefits, you know the brain and beyond.
Cynthia Thurlow: [00:48:42] I love that. And I love the fact that you're focusing more on leg strength as opposed to grip strength, because my legs are much stronger than my hands are. [Dr. Tommy Wood laughs] So I know that grip strength is a proxy for overall strength, but there's not a direct connection there. With that being said, I would love touch on-- it's funny, when I was listening to your podcast, you were talking about fasting. I'm like, we could talk about fasting, but we could also talk about concussions and supplements. And so there's so many things to talk about. So I want to be mindful of time as the parent of all boys and as someone who my kids have played every organized sport you can imagine. And let's talk about concussions, traumatic brain injuries, because it's particularly relevant.
[00:49:25] I know many people that listen to the podcast have shared they themselves or family members have dealt with concussions or TBIs. Let's talk about what's actually happening in the brain when that occurs, and the things we can do proactively if that happens. I know that you talk a lot about thermoregulation, which was new for me to learn about in vis-a-vis concussions and TBIs.
Dr. Tommy Wood: [00:49:47] Anybody who's interested in reading papers, everything I'm about to say is in a paper that we just published very recently that I can send you and you can put it in the show notes. But the first thing to say is that concussion and TBI research historically and still is incredibly difficult to do for two reasons. One is that you never know when it's going to happen generally, there are a few groups where you can pretty much guarantee that it's going to happen. And some studies are done in those populations, like in jump school, like kids jumping out of planes for the first time. A bunch of them get concussions, unfortunately, because they don't know how to land yet. But in general, they're difficult to predict. They're also incredibly heterogeneous. Like every brain injury is different from every other one.
[00:50:31] And so then when you start to think about ways to address that, people get very worked up, and necessarily so about like how severe was this? Which area of the brain is affected? How did it occur? So it's just very difficult to address some of these things. One thing that is important for me to talk about, and I think one of the problems that we've had in terms of generating new therapies for concussions and TBIs is the way that we research them in the lab. And so I'm going to get on another high horse briefly for you. When we study concussions in the lab, in animal models, in general what's done is the skull is opened and something is banged against the brain. There are multiple different ways to do that, but that's essentially what's done.
[00:51:13] Now, the problem is that's not what happens in most concussions, right? When you think about that and when people talk about concussions or TBIs, what they're thinking about is like the brain is like banging against the inside of the skull. That doesn't happen. The brain is surrounded by fluid. And when you have a solid box filled with fluid. Things don't move very much. So what you're actually getting is distortion at different areas of the brain, particularly where you have an interface between two parts of the brain that have a different density. So, like the gray matter on the outside and the white matter on the inside, a big part of that in humans is driven by the gyrification of the brain. If you imagine a human brain, it's super wrinkly. Those are the gyri and then underneath those, where there's some movement, that's where this distortion happens and you can get shearing of neurons.
[00:52:04] In most animals where we study traumatic brain injury in the lab, in rats and mice, they don't have those regions of the brain. So we're studying with the wrong type of injury, and we're studying it in a brain that doesn't have the structures where the injury occurs in humans. That means that a whole bunch of research that's done in this area is probably never going to be relevant to humans, unfortunately. I think that's one of the reasons why we've kind of struggled to get some interventions. Now, there are, I think, a range of supplements and nutritional factors that can mitigate some of the effects of concussions and maybe be used as treatment. And all of them are in this paper, but the important ones are things like Omega-3s.
[00:52:50] So there was a study done in football players where over a season, if they were supplemented with DHA, they accumulated less of a marker of brain injury that circulates in the blood neurofilament light. So any kid who's playing or any person who's playing any kind of sport where there's a risk of concussions, just making sure you're getting enough Omega-3s is a really simple thing to do. Creatine and choline are also similar. So, again, there was a different study in high school football players where they saw that the number of impacts and these didn't have to be significant impacts, just like the number of impacts over a season and they track them with cameras on the side of the pitches. The more creatine and choline levels decreased in certain areas of the brain. And when that happens, particularly with creatine, you may increase your susceptibility to a future concussion, because creatine is really important, like an energy precursor, right?
[00:53:43] Again, getting it, making sure you have choline, creatine, get it from fish, salmon, eggs, meat, those kinds of things or you can take them as a supplement. Then after injury all of those things could potentially play a role. Creatine is probably better before impact rather than afterwards. Again, this is based on some animal research but choline certainly been shown to beneficial Omega-3s. And actually, there is one study in pediatric TBI that suggested creatine was beneficial, so could still be tried if it hasn’t been taken beforehand. Then there are other things that may be head on symptoms. So melatonin if there’s issues with sleep, there are a couple of other supplements that are not just derived from food, things like Boswellia and Enzogenol. And the evidence again is in this paper and its specific to certain symptoms. So it’s not like everybody should take everything. You can tailor it a little bit. Other things like what you mentioned either before or after an impact, other aspects of overall health seem to matter as well. So I think if we think about how homocysteine may play a role in neurodegeneration, then B vitamin status before and after concussion could be important.
[00:54:56] There's at least one study that showed that high doses of riboflavin, which can decrease homocysteine, resulting in benefits. So B vitamins certainly important as well. Then there's the important fact that we know that blood sugar regulation again is an important predictor of outcome after any kind of acute brain injury. And when they look at high school and collegiate athletes, their health isn't great. Even in Division I football players, there was a study that came out a few years ago that showed that about third of them probably qualified for metabolic syndrome. And even the most athletic positions had prediabetes or some issues with blood pressure or something else. So just like attending to the real basics of physical health could improve what happens after a future concussion.
[00:55:49] And there are lots of studies looking at judo players, rugby players, and even at the elite levels, particularly if you're in a sport where size matters and like bigger is better for your sport, it's much more likely that you're going to be in poor physical health metabolically. So attending to those things as much as you can is important and then also minimizing. This is like a hypothesis, it’s not definite, but if you have a very significant traumatic brain injury and you’re in like the ICU, we know that blood sugar regulation is important. So we hypothesize that there’s a sliding scale here and even if this is, “just a concussion,” big spikes in blood sugar are probably not going to be necessarily great for the brain. So don’t start chugging Powerade right after you take a big knock and stuff like that.
[00:56:36] And then the final part is thermal regulation, which you did mention. And my PhD was essentially in how temperature affects brain injury. So this is kind of like my personal interest. But again, there is some evidence from animal studies that suggest that if you’re hot during or after mild TBI, that’s associated with worse outcomes. And we know that if you’re playing football in September in Alabama it’s hot, so these kids are going to be heat stressed at the moment that concussion occurs. So doing whatever you can to minimize heat stress at the time of impact is probably important. And again, I’m saying this is hypothetical. I am involved in some studies now where we going to track heat at the time and then body temperature after a concussion to see how much of a role does this really play? I think it’s going to be important. I can’t give you dozens of big studies in collegiate athletes right now, but hopefully that will happen.
[00:57:33] Because we know that, again, in almost any acute brain injury, if you get hot afterwards, that essentially creates a bigger gap between how much energy your brain needs and how much energy is able to generate, which can then make the injury worse. So it’s just a simple case of avoiding getting really hot either during or after some period of brain injury, which shouldn't be too difficult except for in the final thing. I already said the final thing, but this is already the final thing. One of the best things that you can do to improve recovery after a TBI is physical activity. There's now several trials that suggest that. So in general, at least two or three times a week, some kind of a aerobic, physical activity that doesn't exacerbate symptoms for at least sort of like 20 minutes. That's generally what the trials have used seems to accelerate recovery. Now, of course, if you're worried about getting hot during exercise, you can do things like ice fests and stuff like that to try and get the best of both worlds and some people do do things like that. All right, I think that's everything.
Cynthia Thurlow: [00:58:34] No, no, that's amazing and so helpful. I have a college level lacrosse player and so I'll be having a conversation with him, certainly after our conversation. I just wanted to ask one more question, “Where is the research going?” I know hormone replacement therapy fell out of favor for post WHI, Women's Health Initiative. Now it is seemingly coming back in favor here in the United States. Still, it's only a small subset of the perimenopausal, menopausal population that is taking hormone replacement therapy. But what does the research suggest or show about the role and interplay of sex hormones and cognition and brain health?
Dr. Tommy Wood: [00:59:14] Yeah, I think there's really been this, maybe partly because of the women's concerns raised by the Women's Health Initiative and then you’re just more generally a lack of research into women's health in general. There's been an underappreciation of the importance of hormones on cognitive function, and particularly how those hormones change during the menopausal transition. There's a ton of great work done by people like Lisa Mosconi that really is showing how important this can be. Again, there's no large randomized controlled trial that says, “As you enter menopause, you should get hormone replacement therapy because that will reduce your risk of dementia.” But in, I think, the studies that have been done in the best possible way from an epidemiological standpoint, do you suggest that sensible early initiation of more bioidentical-like hormone replacement can improve cognitive function symptoms if there are cognitive function symptoms? and potentially that may translate to a decrease in dementia later on.
[01:00:19] This is very much going to be personal thing, because, again, you do have to balance overall risk, talk with your doctor all that kind of stuff. There's no really good evidence right now, but all the biology and what we have so far does seem to be lining up. Of course, some of it could be indirect, right. Because if your HRT is improving your sleep, if it's improving how you feel about going out and playing pickleball and going to the gym and all these other kinds of things, I think there are knock on effects of other ways that it could benefit quality of life, which will then also affect long-term cognitive function. But again, this is all kind of like, it's a bit hypothetical just because we don't have really high-quality studies yet, so I can't apply it to everybody, but everything seems to make sense in that direction.
Cynthia Thurlow: [01:01:02] Well, thank you so much. This has been a truly invaluable conversation. Please let listeners know how to connect with you, to your podcast, or learn more about your work.
Dr. Tommy Wood: [01:01:12] Sure. The easiest place to find me probably is on Instagram, @drtommywood, and there I’ll usually post podcasts, papers that are relevant to a general audience. Some of the papers I write are very niche, so don't always share all of them, but certainly things in this area get shared there. And then I do have a podcast, like I said, with Dr. Josh Turknett, who's a neurologist called the Better Brain Fitness podcast, which you can find wherever you get podcasts. It's a question-and-answer style podcast generally, so listeners submit questions, and then we tackle one question every episode. There's a link where you can go and you can either type in a question or you can leave a voice message. We also have a free Substack and if you sign up for the Substack, then we email you, I made this like epically long PDF on different blood markers, specifically around nutrient status and then foods for how to hopefully support long-term brain health. So if you're into any of that, you can get that there.
Cynthia Thurlow: [01:02:08] Perfect. Thank you again.
Dr. Tommy Wood: [01:02:09] Thanks so much.
Cynthia Thurlow: [01:02:12] If you love this podcast episode, please leave a rating in review, subscribe and tell a friend.
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