By Kouros Emami, PsyD
Clinical Neuropsychologist, Hospital for Special Surgery; Clinical Assistant Professor of Neuropsychology in Neurology, Weill Cornell Medical College
In a first of its kind study, researchers found neuropathological markers suggestive of chronic traumatic encephalopathy (CTE) pathology in 41% (n = 152) of young contact sport athletes (< 30 years of age) at autopsy. Clinical measures (obtained retrospectively via informant report) assessing for cognitive and psychiatric/behavioral dysfunction, while elevated across most measures for the entire group, did not significantly differ between brain donors with and without a CTE diagnosis. Functional impairments also were not commonly found.
McKee AC, Mez J, Abdolmohammadi B, et al. Neuropathologic and clinical findings in young contact sport athletes exposed to repetitive head impacts. JAMA Neurol 2023;80:1037-1050.
Chronic traumatic encephalopathy (CTE), a progressive tau-based neurodegenerative disease that encompasses specific neuropathological findings and an associated clinical syndrome (e.g., traumatic encephalopathy syndrome [TES]) involving a constellation of cognitive, behavioral, and emotional dysfunction, has become increasingly synonymous with participation in contact and collision sports and has drawn significant attention by researchers, clinicians, and those in the media. As the current literature stands, CTE only can be definitively diagnosed at autopsy, and the true prevalence of CTE in the general population or in living athletes still is unclear. Additionally, the majority of the CTE research has focused on older groups of retired professional athletes, which potentially can confound findings, given the increased likelihood of age-related comorbidities.
In this study, McKee and colleagues explored the neuropathological and clinical outcomes of repetitive head impact (RHI) in a group of young (22.91 ± 4.31 years of age) contact sport athletes who donated their brains to the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank at Boston University. Of the 152 brains in their final sample, 63 (41%) had an autopsy-confirmed diagnosis of CTE, with 60/63 (95%) diagnosed at either Stage I or Stage II.1
Males overwhelmingly were represented in the sample of CTE brains (62/63; 98%). Those with CTE also were more likely to be older (mean age difference = 3.92 years), identify racially as Black, and have higher levels of education. The cause of death within the CTE brains most commonly was suicide, followed by accidental drug overdose. Of note, there was no significant difference in the cause of death between the CTE and non-CTE brains.
Athletes who played American football overwhelmingly represented the majority of those diagnosed with CTE (48/63; 76%), followed by ice hockey (6/63; 10%), soccer (4/63; 6%), rugby (2/63; 3%), wrestling (2/63; 3%), and professional wrestling (1/63; 2%). Of the football players diagnosed with CTE, 37 played at an amateur level (college and high school), while 11 played in the National Football League (NFL) (11/11 NFL athletes were diagnosed with CTE).
In general, years of play among all football players (n = 92) was associated with a 1.20-times increased probability of being diagnosed with CTE (P = 0.002). Amateur athletes (i.e., not professional or semi-professional) comprised 71.4% (45/63) of the CTE brains. Lastly, there were no significant differences in drug abuse, alcohol abuse, steroid use, or stimulant use between those with and without CTE, therefore ruling out the influence of these comorbidities on disease status.
In comparison to those without CTE, the CTE brains showed significantly more cavum septum pellucidum (26 vs. 19), enlargement of the frontal horns of the lateral ventricles (17 vs. 13), thalamic notching (5 vs. 1), and perivascular pigment-laden microphages in the frontal subcortical white matter (52 vs. 59). Within the 63 CTE brains, characteristic neuropathological signs of the disease also were present, including hyperphosphorylated tau (p-tau) neurofibrillary tangles (NFTs), as well as pre-tangles and dotlike neurites in various cortices (e.g., dorsolateral, superior, and inferior frontal; superior temporal; inferior parietal; and the Rolandic area).
Those with more advanced stages of the disease (Stage II or Stage III) showed further NFT pathology in other brain regions. However, a common neuropathological finding in older individuals with CTE (e.g., subpial p-tau thorn-shaped astrocytes) was not found in this group, which likely indicates a difference in disease process with respect to age. Additionally, within the sample of total football players in the study (n = 92), years of football participation was associated with a 1.26-times (P = 0.003) increased probability of having perivascular macrophages in the frontal white matter.
Neurobehavioral dysregulation, impulsivity, apathy, depression, executive dysfunction, attention and memory, and functional difficulties were retrospectively assessed via informant report. Although symptoms of cognitive (e.g., executive dysfunction in 50% of the sample), behavioral (e.g., 60% had symptoms of behavioral dysregulation), and mood (e.g., 70% had symptoms of depression/apathy) dysfunction were present across the entirety of the sample (n = 152), there were no significant differences between those with and without CTE for any of the clinical measures. Additionally, functional difficulties were not a common finding in this study.
COMMENTARY
Contact and collision sports inherently expose athletes to RHIs and, thus, increase their risk of brain injury and the potential for neurodegenerative diseases such as CTE, as found in 41% (63/152) of young athletes. Although the findings of this study are novel given the age of the participants, it also is important to note that not all athletes with a history of RHIs developed this disease. In fact, the majority of this sample (59%) did not. Additionally, the clinical symptoms, while present as a whole, were no more prevalent between the CTE and non-CTE groups. It may be that these issues become more prevalent as a function of time. In living patients with sport-related head injuries, effective treatments have been developed. Continued research into CTE is encouraged to better understand the disease in living individuals.
REFERENCE
- McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013;136:43-64.
