Study Finds High Prevalence of CTE, Other Disorders in Former Football Players

Recently, the Boston University Chronic Traumatic Encephalopathy (CTE) Center conducted a thorough analysis of 202 brains donated from former football players whose careers ranged from high school to the National Football League (NFL).

The study, published July 27 in JAMA, made headlines for the high prevalence of CTE uncovered: 177 of the brains (87 percent), including 110 of 111 NFL players, had a positive CTE diagnosis. However, lead author Jessie Mez, M.D., told Psychiatric News that these numbers have overshadowed some of the important discoveries about this progressive neurological disorder characterized by a range of behavioral and cognitive problems.

“The study was not designed to assess the prevalence of CTE,” said Mez, an assistant professor of neurology at the BU CTE Center. “Our goal was to characterize the neuropathology of this disorder and understand how it manifests and progresses, and how the pathology relates to clinical symptoms.”

As was noted in the paper, most of the brains analyzed were donated to the brain bank because the football players or their families were concerned about possible CTE. Therefore, the findings do not suggest that a career in the NFL is a guarantee of developing CTE in later life, he said.

Nonetheless, the differences in CTE pathology seen among players with the varying lengths of play reinforce the idea that longer playing time does increase the risk of CTE and its potential severity. All three high school football players who were diagnosed with CTE had mild pathology, whereas many college and professional players had severe pathology (56 percent and 86 percent, respectively). The findings suggest that while the onset of CTE is not an absolute for someone with a long football career, it is a very real possibility, Mez said.

However, the larger public health concern, which was underplayed by many media outlets, is that the long-term effects may be evident even in individuals with short-term football careers, said Gil Rabinovici, M.D., a professor of neurology at the University of California, San Francisco, who wrote an editorial accompanying the JAMA study. “The fact that the Boston group identified CTE in many people who stopped playing in high school or college is concerning, since this represents a much larger population than professional players.”

Another finding overlooked in the media coverage, Rabinovici said, was the presence of other pathologies in these samples. “Only around half of these brains had [brain pathology indicating] purely CTE,” he told Psychiatric News. “The others also had signs of Alzheimer’s, Lewy body disease, or other disorders.” He noted that this high prevalence of multiple pathologies was unusual given the younger age of the brain samples (the average age of death was 66) and hints that these injuries might make football players susceptible to a range of problems.

Retrospective autopsy samples can tell only so much, Mez pointed out, and studies in living patients are needed to address questions such as the link between CTE and other neurodegenerative problems. Another important question is why there appears to be a discrepancy between the brain pathology and the psychiatric symptoms reported by individuals with CTE.

In brain samples of severe CTE pathology, there was noticeable accumulation of abnormal tau protein in the hippocampus and amygdala (both known to be involved with emotion) in players who reported symptoms including impulsivity, anxiety, depression, and explosive outbursts. This tau buildup was not evident in mild CTE cases, but the former players who had mild CTE reported mood and behavioral problems just as frequently, Mez said. (As part of his role at the BU CTE Center, Mez interviews family members of the deceased players to catalog their behavioral history.)

“It points to some other contributor that we cannot characterize in these postmorten samples, such as changes in the blood-brain barrier or neuroinflammation induced by CTE,” he said.

What Mez and his colleagues did ascertain from their interviews is that CTE might present in one of two clinical forms. While almost all the CTE cases had mood or behavioral problems by the time of death, there was a split in when these symptoms emerged, with some patients first reporting behavioral problems while others first displayed cognitive problems or dementia (a small subset presented with both).

Those findings match what Rabinovici has seen in his clinical experience, with two different CTE presentations depending on age.

“When we see older football players who played decades ago, they complain mostly of cognitive problems that resemble early-stage Alzheimer’s,” he said. “Younger players, on the other hand, typically come in with behavioral problems such as depression, suicidality, and substance use.”

Rabinovici noted that this dichotomy in symptoms could represent one of two possibilities. It could be that CTE has distinct subtypes in which cognitive or behavioral symptoms emerge first. For instance, it is possible that not enough modern NFL players have reached ages where a cognitive-first CTE would appear, whereas many older players who developed behavioral problems years ago would likely have been misdiagnosed with other disorder.

“But, the sport has changed so much in terms of how the game is played, equipment, and the force of impact that we might be seeing a shift in how this disorder manifests,” he said.

This study was supported by multiple grants from the National Institutes of Health, U.S. Department of Defense, and U.S. Department of Veterans Affairs. Additional support was provided by the Alzheimer’s Association, the NFL, the Concussion Legacy Foundation, and others. ■

“Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football” can be accessed here. The accompanying editorial, “Advances and Gaps in Understanding Chronic Traumatic Encephalopathy,” is available here.