CTE Prevalence High...and Not Just in Athletes

Nearly 6% the general population may have chronic traumatic encephalopathy (CTE), new research suggests.

Results from the largest and broadest study of CTE to date show that although the highest rates of the disease are in athletes, a significant number of nonathletes have the neurodegenerative disorder.

"While frequency of this disorder is not as high in amateur athletes compared to professional athletes, CTE pathology — of various levels of severity — is still observed in small, yet significant, number of cases," lead author Kevin Bieniek, PhD, director of the Brain Bank, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health, San Antonio, Texas, told Medscape Medical News.

"Identifying sports with higher frequencies of this pathology, in this instance football, will help inform our practice of making these activities safer for participants by mitigating sources of injuries and properly treating them when they occur," he said.

The study was published online June 14 in Brain Pathology.

Debilitating, Enigmatic

CTE is "a debilitating and enigmatic neurodegenerative disorder associated with repetitive traumatic brain injuries, often sustained through prior contact/collision sport participation or military-related exposure," the authors write.

"Given that approximately 28 million children (≤15 years old), 8 million high school athletes, and 500,000 collegiate athletes participate in organized sports programs annually in the United States alone, research regarding whether playing specific sports (especially at the amateur level) is associated with an increased risk of developing CTE pathology is imperative," they add.

"Previously, many CTE studies were performed with a small number of cases or in cohorts of selectively recruited professional athletes. We were motivated to conduct a study aiming to provide evidence regarding the pathological epidemiology of this disorder — or, in other words, how frequent this disease might be in the general population," Bieniek said.

To investigate, researchers retrospectively assessed participation in specific sports in conjunction with use of the Mayo Clinic Tissue Registry, a large autopsy cohort (n = 2566 .

They assessed sports participation for each subject, determined on the basis of information from obituaries and high school yearbooks. They included individuals for whom information from both obituaries and high school yearbooks indicated that the person had not participated in sports; and individuals for whom obituaries, yearbooks, or both revealed participation in ≥1 sport.

The final sample size consisted of 750 persons (300 athletes and 450 nonathletes).

The researchers utilized the Rochester Epidemiology Project database, a medical records–linkage system of healthcare providers in Southern Mississippi and Western Wisconsin, to glean diagnostic codes for head trauma; dementia; movement disorders; alcohol, tobacco, and drug use disorders; anxiety; depression; bipolar and posttraumatic stress disorders; psychosis; schizophrenia; and suicide.

Of the 477 males included in the study, 232 (49%) played at least one contact sport. Football was the most common (29%), followed by basketball (19%), baseball (13%), and wrestling (8%).

Of the 273 females included, 66 (24%) played ≥1 sport, with participation in girls' athletic associations (15%), basketball (5%), and baseball/softball (3%) being most common.

Tau pathology consistent with CTE consensus neuropathologic criteria was identified in 21 males (2.8%). The burden of neocortical tau pathology varied from marked to mild.

An additional 21 persons (20 males, 1 female) were designated as having "features of CTE."

In total, combined CTE pathology was observed in 5.6% of the cohort.

177 persons (23.6%) had tau-immunoreactive neuritic plaques, pathognomonic of Alzheimer disease.
15 persons had both combined CTE pathology and Alzheimer disease neuritic plaques.
605 persons had ≥1 tau-immunoreactive lesions.
145 study persons were entirely free of tau pathology in the cortical sections that were evaluated.

To avoid potential confounding by sex, the researchers compared persons with and those without CTE pathology only among males.

They found that in comparison to CTE-negative males, males with combined CTE pathology tended to be older at death (P = .006) and to have a lower likelihood of anxiety (P = .029).

However, in males with combined CTE pathology, there was a higher likelihood of dementia (P = .017), movement disorders (P = .024), psychosis (P = .005), and Alzheimer disease neuropathology (P = .027).

In secondary analysis, the researchers excluded the 26 CTE-negative males (5.5%) who were younger than 30 years at the time of death. They found that the statistically significant differences in characteristics that were observed between CTE-negative males and those with combined CTE pathology remained significant in this subset of males whose age at death was ≥30 years (for all, P ≤ .033).

Football a Main Culprit

Multivariable analysis showed that football was the only sport significantly associated with increased odds of combined CTE pathology in males (odds ratio [OR] = 2.62; P = .005).

Although not significant after correcting for multiple testing, CTE positivity was more common for persons who boxed and for those who played football.

Playing football beyond high school was associated with substantially increased odds of combined CTE pathology in multivariable analysis (OR = 13.23; P < .001). There was a similar, albeit weaker, association when considering only CTE positivity (OR = 6.84; P = .0056).

The odds of combined CTE pathology and CTE positivity in football players vs non–football players were not significantly increased in multivariable analysis for persons who participated only in youth or high school football.

Playing two or more sports was not more strongly associated with combined CTE pathology or CTE positivity (OR = 1.30, P = .55; and OR = 0.96, P = .94, respectively).

By contrast, the association of playing football with combined CTE pathology was found to be consistent after adjusting for playing multiple sports in addition to age at death, with similar results found for CTE positivity.

"Importantly, we observed that participation in American football, specifically American football beyond high school, was associated with a markedly increased odds of both combined CTE pathology and CTE-positive outcomes in males," the authors write.

On the other hand, "though participation in football that did not extend beyond high school was associated with an approximate two-fold increased risk of CTE outcomes, these statistics were not statistically significant," they add.

The researchers note that although the findings suggest that playing youth or high school football "may be associated with a slightly elevated risk of CTE (larger studies are needed to confirm this), they also indicate that most players of youth or high school football do not experience CTE outcomes."

Major Public Health Issue

Commenting on the study for Medscape Medical News, Carmela Tartaglia, MD, Marion and Gerald Soloway Chair in Brain Injury and Concussion Research and associate professor, Tanz Center for Research in Neurodegenerative Disease, University of Toronto, Ontario, Canada, who was not involved in the research, described it as "very important," noting that it furthers the understanding of the prevalence of CTE in the general population.

The study "highlights that there are many unknowns in this neurodegenerative CTE — as, although CTE was observed, it was much, much lower than what has been reported in some series, and there was some CTE also found in nonathletes," she said.

The study "highlights the need for prospective studies, as it is very difficult to recall the number of concussions in the general population and in former athletes from a time when concussions were not being recognized," she observed.

Moreover, "the pathological diagnostic criteria for CTE need to be scrutinized, given the recent description of ARTAG [aging-related tau astrogliopathy] has some overlapping features with CTE."

She added, "Contact sports, especially football, increases the risk of CTE, but there is no clear relationship, as many former athletes did not get CTE."

There is "a need to investigate this relationship extensively to understand what makes people vulnerable," she said.

In a press release, Bieniek noted that 42 cases, or 6%, "might not seem like a lot, but when you consider there are millions of youth, high school, and collegiate athletes in the United States alone who play organized sports, it has the potential of being a significant public health issue."

The study was funded through grants by the Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program, the Mayo Clinic Younkin Scholars Program on Synaptic Biology and Memory, and the Mayo Clinic Alzheimer's Disease Research Center Pilot Project. Bieniek and coauthors have disclosed no relevant financial relationships.

Brain Pathol. Published online June 14, 2019. Abstract

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