Q&A Part 2: CTE Prevalence, Brain Donation Findings in Former NFL Players: Thayne Munce, PhD

While research continues to provide insight into chronic traumatic encephalopathy (CTE), significant questions remain about the condition, including how it develops, why some individuals may be more susceptible than others, and how its pathology translates to clinical symptoms during life. Because CTE can currently only be definitively diagnosed through postmortem neuropathological examination, researchers face limitations in tracking the disease prospectively and identifying factors that may influence its development.

For former NFL players, those questions also need to be considered within the context of changing eras of football. The players examined in recent research largely competed decades ago, when exposure to repetitive head impacts, concussion recognition, equipment, practice structures, and access to sports medicine care differed substantially from what is available today. As a result, questions remain about how findings from historical cohorts should inform our understanding of CTE risk among current players and athletes competing at younger levels.

In this second part of his conversation with NeurologyLive^®, Thayne Munce, PhD, discusses the limitations and unanswered questions that continue to shape CTE research, including the need for better ways to study the condition during life and identify potentially protective factors. He also discusses what the evolving understanding of repetitive head impacts may mean for current and youth athletes, and why continued efforts to improve the safety of football remain important.

NeurologyLive: What did you think were some of the limitations of this study, and how could these results expand beyond just NFL players?

I think we probably touched on some of the limitations already, just in terms of having to estimate what the overall prevalence rates are in that broader cohort of former NFL players because they only had access to the brains that were donated. They weren't able to evaluate all of the players, and that's where you ended up with such a broad range.

They mentioned in the paper that they're fairly confident that they captured most, if not all, of the deaths that happened. There could certainly have been some former NFL players who maybe never made it into certain registries or certain databases that could have been queried. So, the denominator, the number of overall players, may have been different from what they were actually able to account for.

Also, some of the dementia diagnosis was done retrospectively. They had a blinded group of neuropathologists who didn't have any access to the clinical history and background. Then they had clinicians who didn't have any access to the neuropathology who were doing this retrospective diagnosis of dementia and looking at medical charts.

I can't recall in this study, and I know in past studies they've used interviews with family members, but it's still working backwards at making that diagnosis. Rather than, again, if you're doing a prospective study where you're enrolling individuals and taking them through a very rigorous battery of assessments and clinical diagnoses while they're living, you can document with more certainty whether someone has a certain condition.

This was retrospective, both in terms of the neuropathological assessment as well as the dementia diagnosis. There were certain individuals within that group who had been diagnosed with dementia while living, and they reported cause of death on death certificates among the participants.

They didn't use that as verification, butrather characterized what percentage of individuals who were diagnosed with dementia after death actually had that listed as a cause of death on their death certificate or were diagnosed with dementia while living.

Those are some of the limitations in a retrospective study like this. It's something that researchers just have to explain and work with.It's really not a fault of the researchers or the study design.It's the inherent limitations of doing a large retrospective study such as this.

Looking ahead, what are some of the questions this study raises for future CTE research, and what are some of the most important unanswered questions in the field?

I'd like to jump to that second question first because the biggest limitation in the entire area of CTE research, at least in my view, and I think others may agree here, is this inability to diagnose CTE in the living.

That makes it so that we have to do these retrospective studies and don't have the ability to prospectively enroll participants, track disease progress, and look at other comorbidities and other factors that would be really useful to get a better understanding of this disease. So that's the biggest gap.

I think one of the other steps forward, while we are still doing retrospective studies, is trying to capture as much information as we can about other contributing factors, whether that's lifestyle, physical activity, nutrition, drug use, drug abuse, alcohol, cigarette use, and genetics. Looking genetically at whether there are differences that may be helpful in predicting who is more likely to develop CTE.

I think one of the more interesting questions that often doesn't come out through these studies is that even if you find 95% of your donor group has CTE, what's unique about that 5%, or that small percentage, who doesn't have CTE but may in many other characteristics match up with your donor group?

Is there something genetic? Was there something protective about that individual that kept them from developing the disease, or was that just good luck?

I think those are some of the questions. If we could uncover if there are any neuroprotective characteristics, whether that is genetic or nature versus nurture or behavioral, whatever that may be, that certainly would be very useful for current players and future players.

That could be whether it's screening or advice or guidance in how they approach their participation in activities that have increased risk for repetitive brain trauma, where a condition like CTE may be on the back of somebody's mind.

Do you have any lingering thoughts or final thoughts on the topic that we haven't directly covered?

I would just like to reiterate again that I think this is really important work. These studies need to continue.CTE, as a lot of these authors and researchers have reported, is not a football-only type of disease. Just like with concussion, concussion is often linked with football, but there are a lot of other sports and recreational activities and military activities that have also been associated with some of these brain diseases and brain trauma.

So, it's really important work that needs to continue. I would want to go back to some perhaps public-messaging types of statements for parents of youth athletes or current football players who may see this study and the headlines and wonder, what does this mean for me?

Seeing that 25% or more of former NFL players had CTE, and possibly even greater than that, could be pretty sobering for a current player or a parent who's thinking about whether their child should start playing this sport. It seems pretty daunting.

Just a couple of points of consideration and reassurance: Again, this is historical. The exposure to repetitive head impacts and the availability of medical care, the equipment that was used, the practice structure, and the way in which concussions were really even recognized and were often dismissed in the past have changed.

I don't think there's a safer time to be playing the sport of football because of the advancements that have been made. I think that this study just reinforces all of those good efforts that have been made over the years to say, OK, there is an association here that's been identified and it's linked to repetitive head impacts. What can we do to reduce that risk? What can we do to try and promote the health and safety of players into the future?

A lot of those efforts have been underway, and I think have changed the game in a very positive manner.

We don't know whether the risk of CTE for current NFL players is the same, more, or less than in players in the past. I would suspect that it's lower because of all of the reasons that I mentioned, but we don't know for sure.So, the work has to continue.

I would also tell parents of high school players and youth players to recognize that whatever risk exists for an NFL player, including CTE risk, is vastly different from the risk of injury and the risk of developing disease for high school and youth players.

It'srather well accepted that CTE is associated with cumulative exposure to brain trauma. Therefore, it's reasonable to expect that people who have lower cumulative exposure to repetitive head impacts and brain trauma will be at a much lower risk for developing this disease.

Studies, including some work that my group has done, have shown that the frequency of impacts in particular, and severity to a lesser extent of head impacts, but certainly the cumulative exposure to the head impacts over the course of a youth football season and a high school football season are considerably lower than at the collegiate level, and presumably lower at the professional level.

That's not to say that it's OK to get hit in the head and that you shouldn't worry about that. Rather, the level of exposure is greatly different at different levels of play.

If you are fortunate enough to be in that small percentage of football players who make it from high school to college to the NFL, you've accumulated a lot of exposure and a lot of trauma along the way. That puts you in a unique situation that's much different from the exposure that someone who plays 2 to 3 years of high school football, or even a couple of years of youth football and 3 to 4 years of high school football, is ever going to experience.

So, that would just be a message that I would want to share with individuals about the concern about CTE. We need to take care of athletes' brains. We need to do everything we can to make the game as safe as possible. But we also have to keep it in perspective that football is not all the same. Different eras of football are different. Different ages of football are different.

Transcript was edited for clarity.

REFERENCES
1. Daneshvar D, Nowinski C, Abdolmohammadi B, et al. Prevalence of chronic traumatic encephalopathy at death in National Football League players: retrospective population based cohort study, 2008-21. BMJ. 2026;394. doi: 10.1136/bmj-2026-100418