Professional Athletes Brain Health Study: The First 10 Years

Podcast Transcript

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: The Professional Athletes Brain Health Study was initiated in 2011, to examine the cumulative effects of repetitive concussions and sub-concussive impacts to the brain in a group of professional fighters. The study has since broadened to include athletes in other sports exposed to repetitive head impacts, like professional bull riders, and is the first to study active and retired athletes concurrently. In today's episode of Neuro Pathways, we're discussing the findings in the first 10 years of this longitudinal study and what's to come. I'm your host, Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. And joining me for today's conversation is Dr. Charles Bernick. Dr. Bernick is a Neurologist in Cleveland Clinic's Neurological Institute's, Lou Ruvo Center for Brain Health in Las Vegas. Charles, welcome to Neuro Pathways.

Charles Bernick, MD, MPH: Well, thank you very much. It's a pleasure to be here.

Glen Stevens, DO, PhD: So, tell our listeners who don't know you so well, a little bit about yourself, how you decided that this was going to be the area that you wanted to study in your training, just so we can understand you a little bit better.

Charles Bernick, MD, MPH:

Well, I'm a neurologist and got into the field of Alzheimer's disease and neurodegenerative diseases actually close to 30 years ago, when it wasn't such a hot topic at that time, which it's grown to be. And among the neurodegenerative diseases that I've cropped up and have gotten a lot more attention lately because of the notoriety of the people that get it is this chronic traumatic encephalopathy, which is the result in many cases of extensive exposure to head impact. So, football players are the most notorious to get it, but you could see it in any of these contact sports. And the problem is, Glen, we just know very little about it.

Glen Stevens, DO, PhD: So I saw on TV the other day, I was watching one of the football practices and they have the new helmets, these guardian helmets. Which is interesting because now in our baseball teams now called the Guardian. So, it struck my attention that they called the guardian helmets, but it looks like a foam padding that goes on the outside of the helmets. Do you know much about that? Can you tell me anything about that? I know it's a little bit off from what we're discussing today, but I found it interesting.

Charles Bernick, MD, MPH: Yeah. There's been a whole industry really looking at how you can actually intervene early, I mean, be before people get these long term effects of head injuries and of course, that that is trying to reduce the impacts on the head with hits. And so there's been a variety of helmets that have been developed and the idea is to try to reduce that impact. The problem is with concussion and even sub-concussive hits, it's really stopping the movement of the head. that is the problem. So, the force of the impact is one, but and then the other is the velocity of how the head is moving on the neck. And these helmets probably help to some degree, but that's still going to be a big issue.

Glen Stevens, DO, PhD:Yeah. And I don't know for sure and it's a little bit off topic, but I suspect that a lot of the high schools around nowadays are doing a lot less contact drills to try to decrease these sub-concussive events, those types of things.

Charles Bernick, MD, MPH: Yeah. Absolutely. Actually, I'll say this, I think, in the future we're going to see a lower incidents in prevalence of CTE, Chronic Traumatic Encephalopathy because of these interventions that are being made now.

Glen Stevens, DO, PhD:So that sounds like a good thing. So, I'm happy to hear that I played high school football, I didn't play after that. Played up in Canada. It's not really the same football as in America, but the hitting is the same in the head injury is the same. So hopefully I didn't have too much of an issue at that point in time, but I guess, time will ultimately tell with it. Tell us about this study and how it came to be. We have a decade's worth of data, so we'll get into that. But tell me how it came to be and how it transitioned because initially in fighters and then expanded.

Charles Bernick, MD, MPH: Yes. So the seed of this study really began in early two thousands. At that time there was more and more information coming out about the pathology of chronic trauma encephalopathy. And of course there were a number of very tragic cases that got a lot of publicity of people who died with a CTE. We felt that this is a disease that needs to be studied more. We are in Las Vegas and Las Vegas is the fight capital of the world.

And I think, many of us in medical school probably passed over the concept of dementia pugilistica and then never thought about it anymore, but of course CTE was first described in boxers and again we felt we had the opportunity to actually recruit and retain a large number of professional fighters, both boxers and mixed martial artists to really understand the natural history of what happens when people are exposed to repetitive head impacts.

So, it took us a few years to put all our networks together and we were very pleased that the combat industry was quite accepting of our interest in studying it. So, the Nevada Athletic Commission, the major promoters including the UFC and Top Rank boxing and others. It actually, came together around 2008, 2009 and got us some funding along with then the Cleveland Clinic pitched in and we were able to watch this study in 2011, but that's when we started enrolling participants.

So, the idea is to make it like a Framingham Study of repetitive head impacts and try to understand on long-term the natural history, how things develop, risk factors, biomarkers and eventually, of course, interventions that we can do to reduce the risk of this disease.

Glen Stevens, DO, PhD:And when do individuals enroll in this study? Could it be those that are done their fighting career or early on in the middle of it?

Charles Bernick, MD, MPH: Yeah, Glen. I think, we took the tact that CTE is probably other neurodegenerative diseases such as Alzheimer's and Parkinson's where we know the disease process actually starts in the brain years before you have any symptoms. So, we really wanted to try to understand the whole development of this condition.

So, we intentionally said, "All right. Certainly, would be interested in retired athletes who had extensive exposure" but what we really want is active participants as well, active fighters. To understand again what happens as they're actively exposed to head impacts as well as what happens when they stop fighting and when this transition period occurs because some people probably will continue to progress in the changes that occur in the brain and some people won't. And being able to identify those differences can be, of course, huge in how we would approach treatment.

Glen Stevens, DO, PhD:And what have you found with individuals? People go running the other way, they come running towards it. My guess is, that they're not interested in anything that would stop them from doing something that would've allow them to make a living. And I'm sure that there's some degree of apprehension that someone's going to tell me I can't do this and this is how I make a living or have you not found that as a problem?

Charles Bernick, MD, MPH: Interestingly, it hasn't been a problem and I think, it's how you frame it. We make it clear to the participants that first of all, the information we gather is confidential. So it doesn't go to the promoter, it doesn't go to the Nevada Athletic Commission, we share it with the participant and that's it.

So, they've hopefully feel assured that nothing we discover is going to have any direct consequence to their career. And I think, a lot of people are actually interested in their own brain health. Many aren't, to be honest with you. So, many join the study because they get an MRI scan for free, which they can use for getting their license to fight.

And there's other reasons, many reasons why people participate. But I think there, there's a subset of individuals and those probably who have stuck with this over the 10 years who actually do have some interest and do want to know if they're getting damage to the brain. They want to know it and make decisions accordingly.

Glen Stevens, DO, PhD:So, tell me the things that you're measuring. Do you check MRI, do you do it lumbar punctures on anybody? Are you measuring blood biomarkers of head injury, things such as tau, do you do neurocognitive testing? Tell me the tests that you run on these folks?

Charles Bernick, MD, MPH: All of the above. So they get annual imaging, well actually, after a while it's every other year but they get MRI scans on a regular basis. And interestingly, in Cleveland, have your 7T MRI scanner and we have done a substudy looking at how 7T MRI compares to 3T MRIs. So, that's quite an interesting substudy.

And the subset have had PET/tau imaging, just as you brought up tau, protein is one of the characteristics pathologically of CTE. Son we've done studies with petal imaging, we do blood biomarkers. We perhaps had some really interesting findings that hopefully will be published soon about some of the biomarkers that we're looking at. Neurofilament light, GFAP, we do measure various tau species as well. They get speech samples, which is an interesting biomarker that's being studied by our collaborative group at the University of New Mexico.

They get behavioral questionnaires, they get computerized cognitive testing. So, our goal really was to throw a large net trying to look at what could be potentially helpful to us as we go forward. Again, as far as indicators of some process that actually may be progressive in the brain.

Glen Stevens, DO, PhD:Anything you can tell us about the 7T?

Charles Bernick, MD, MPH: Yeah. 7T is really interesting as you might imagine. So, particularly, with white matter lesions, you definitely can detect more on 7T Imaging. Hard yet to know again if that's going to have a clinical value but there's no question that you can detect more change with 7T than with 3T.

Glen Stevens, DO, PhD:Are you seeing micro hemorrhages?

Charles Bernick, MD, MPH: No. Interestingly, that there's no difference in that between the two modalities. So it looks like 3T MRI can pick up micro hemorrhage as well as the 7T. And also counterintuitive, the micro hemorrhages are much more common in fighters than in controls.

So, the things that we really see, I guess, that differentiate the two controls and fighters are more related to volume changes, white matter integrity, DTI, for example, sequences, resting state conductivity. So, some of these both functional and structural changes.

Glen Stevens, DO, PhD:And is the structural change or the atrophy, is it asymmetric? Is it temporal lobes, is it variable?

Charles Bernick, MD, MPH: Yeah. Well, that's another interesting thing. In our active fighters we see most of the volumetric changes in the thalamus and corpus callosum. So these deep structures that either carry a lot of fibers or are connected to a lot of fibers yet in the retired fighters it's actually the changes we see over time are in hippocampus and a amygdala.

And so, we think there may be in some sense two things we're seeing. So, in active fighters you're seeing just the result of axonal injury, tumor axonal injury. Whereas in retired fighters, those that show these progressive decline in hippocampus and Amy amygdala may have the development of a neurodegenerative process. And that's trying to actually develop some type in some sense of classifier using a variety of MRI measures to be able to predict who may be actually on a progressive course.

Glen Stevens, DO, PhD:How many subjects in your trial?

Charles Bernick, MD, MPH: So we have 800 participants, we'll a little over that now, about 100 of them are controls and then about 100 are retired fighters. The rest are active. But what's neat is there are both men and women because in a lot of these studies certainly, of course, of football you don't have any women.

So, we don't really know if there's any differences by gender or sex. And the other thing of course, just the nature of our cohort is it's very diverse racially and ethically. To that point, one of the areas that we're really interested in is early life, psychosocial social economic type of differences that may put individuals maybe at a higher risk of certain things.

Glen Stevens, DO, PhD:So it's been a decade. How long are you going to follow these patients for?

Charles Bernick, MD, MPH: Well, that's a money issue as long as we can keep it funded, would like to keep it going. Clearly the most important information we get from this project will be this data that we're accumulated over time. And you'd say, "Well, 10 years is a pretty long time," but in a disease process that probably goes over three or four decades, I mean, it's probably not a long time.

And so, we have a core of people who've stayed in there, a couple hundred. Who are very committed and I think, we'll keep it going as long as we can. We do have funding for another five years and we do have plans to add a few things and an autopsy component, which of course is critical to understand really what we're seeing as well as I've mentioned some of the further work into socio-economic, psychosocial, these type of influences on the outcomes.

Glen Stevens, DO, PhD:And are you adding new patients still or not adding new patients?

Charles Bernick, MD, MPH: No. We are definitely adding and replenishing the till. We're particularly interested in certain groups, so retired fighters, we would like to have more retired fighters. We have a lot of course active. Retired fighters, women, we need actually more controls that are matched a age and education wise. So we'll keep the enrollment rolling forward. Although that the biggest emphasis now is the retention part.

Glen Stevens, DO, PhD:Have you found anything that's surprised you?

Charles Bernick, MD, MPH: I don't know if anything surprising to be honest with you. I think, what's the most recent things will be published in neurology is looking at actually individuals who went into the study as active fighters and then retired while in the study.

So now, we have when they're actively exposed and when they're not. And the good news is a lot of them get better or stabilize at least in the short run. So now whether a subset of those people are going to then revert and continue to get worse, that's really going to be the interesting question which hopefully, will be able to answer.

Glen Stevens, DO, PhD:And obviously a very complicated question to answer at this point in time, but anything that we can do to prevent, other than obviously decrease in the number of hits to the head, anything we can do to prevent development of problems down the road?

Charles Bernick, MD, MPH: Yeah, I think it all really does involve reducing the hits in the head or understanding a better way in terms of training. So for example, it may be that somebody can tolerate sparring for a certain amount of rounds per week or playing having contact you drills for a certain period of time and then there needs to be a rest period or how to deal with return of play.

And I think, there's a lot of these issues of letting the brain repair itself because we know that if you had a concussion then you are more likely to have another one within a short period of time if you're continue to be exposed. In other words, there's this vulnerability and if we have a better understanding of how much time it takes for the brain to recover or inflammatory changes to go down or are there ways that we can reduce whatever is happening that increases that susceptibility to further injury.

So I think that's going to take a lot of work. But I think along with just these common sense rules of limiting contact and the age at which you start a sport, I think, we'll be able to drill down a little better as far as the training methods and advice to athletes that do this for their career. And by the way, Glen, I would say this, we talk about athletes because they're the most visible, but there's a lot of work on military and blast exposed injuries and that a lot of it mimics the same thing. So it's not quite the same. But I think that there may be a generalized general liability of some of these findings.

Glen Stevens, DO, PhD:Have you seen any change in gloves development over time? Are boxers using more padded gloves, Does that decrease the amount of force or not necessarily?

Charles Bernick, MD, MPH: Yeah. Not necessarily. Well, it may reduce a little bit of the, so the force though, it does provide a bigger area to hit. And again, I think, it's that movement of the head, the torsional movement. Which seems to be damaging. And so probably again with boxing it's just reducing the number of hits that a person suffers from. And it's also interesting when we looked at both our MMA and boxing cohorts. The MMA people always come out better and it's probably because they really don't get hit as much. I mean that's not the total intent of the sport.

Glen Stevens, DO, PhD:And any data on skull thickness or as you mentioned earlier, is that the movement of the soft tissue within the calvarium, that's the problem. If you have a thicker skull, is that better or any data or any data?

Charles Bernick, MD, MPH: That's a really interesting point because you always hear about people that could take a blow and so why is that? Is it just something anatomical? And this brings up, of course, woodpeckers we're constantly hitting their head, but so is there something anatomical that has a protective effect? We've talked to our neural radiologists about this, whether there was ways to measure that and I guess, it's a hard thing to measure, but that's a good question whether there is just some anatomical features that actually protect individuals or reduce their risk.

Glen Stevens, DO, PhD:So think, and again this is hypothetical down the road type of stuff, but do you foresee a point in time that somebody would have a liquid biomarker, whether it's tau or the neurofilament light chain and they would have a blood test done before a fight and if it's at a certain level then they won't be able to fight? Or is this something that's not a prime time thing?

There's too much variability between people or I suppose you could say, hey, this is your baseline so you would know what a change from your baseline is and if it really correlates or not. Or am I thinking about things that way too far in the future to know?

Charles Bernick, MD, MPH: No. I don't think it's that far in the future. I think, the neurofilament light we've actually discussed with the UFC as far as looking at that again to help training really neurofilament light will go up after acute injury. And so, you could test it on a weekly basis during a somebody's camp. A eight weeks camp of training before a fight and actually adjust training based on a neurofilament light. I think, what we're finding out about this other marker GFAP, is that elevations of it over time are correlated with volumetric loss and cognitive changes. So, it maybe at least, would be tired athletes that you could follow GFP over time and for example, if you see it going up longitudinally. Then that may be a sign or a signal of, again, a process going on. So I don't think it's that far off. I think, we need to understand it a bit more and also be able to test it in other cohorts that are exposed to head injuries, but I don't think we're that far away from it.

Glen Stevens, DO, PhD:Any other data that is around that you care to share with us that we haven't discussed?

Charles Bernick, MD, MPH: Yeah. I think, the biggest things that we're excited about is one, the MRI findings and what are the features that may be helpful that these fluid biomarkers and how they play out. And the other part that we're really looking at now is things like genetics, are there genetic factors. We're working with folks at Lerner, Dr. Bekris, for example, on neuroinflammation and actually methylation of DNA and such to really drill down and we may be able to have biomarkers that could be useful in terms of again, predicting or detecting people who may be developing CTE.

Glen Stevens, DO, PhD:So, I used to do some work the decades ago with fighter pilots and they're very apprehensive because they don't like you to test anything on them would then stop them from being

able to fly. And I'm sure there's some degree of that with the boxers as well, right? That the fear is you're going to find something, you're going to say they can't do it but it sounds like at least in your group, people have been very open to this and you have confidentiality within the study.

So, sounds like very exciting stuff. Looking forward to these papers that are coming out and the continued success that I'm sure that you'll have and hopefully will change how training is done, decrease the risk that a lot of these athletes have as they get older. So I'm quite excited about the work that you're doing. I really appreciate your joining us today.

Charles Bernick, MD, MPH: Well thank you very much and I really appreciate the opportunity to share some of these fighting with your audience. It is very exciting to us.

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