Association between contact sports participation and chronic traumatic encephalopathy: a retrospective cohort study

Abstract

Chronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non-athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records-linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non-athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P-value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports-related repetitive head trauma.

Keywords: chronic traumatic encephalopathy; contact sports; football; tau; traumatic brain injuries.

Figure 1

Study workflow. Obituaries were queried for all consented autopsy cases in the Mayo Clinic Tissue Registry from 2005 to 2016 (irrespective of any clinical or pathological diagnoses) with cortical brain tissue. Gray boxes denote a query while red boxes represent case exclusion. Obituary data were used to identify yearbook records. Together, contact sports participation was assessed from these historical primary sources, identifying 300 athletes (various sports) and 450 non‐athletes. Subsequent assessment via tau immunohistochemistry ascertained presence or absence of CTE pathology.

Figure 2

Chronic traumatic encephalopathy (CTE) pathology. CTE is characterized by focal deposition of hyperphosphorylated tau protein (brown signal) in neurons (black arrows) and astrocytes (green arrows) around penetrating blood vessels (blue arrows) at the depths of cortical sulci, as shown here in two cases (A,B). CTE pathology can be observed concomitantly with Alzheimer's disease pathology, namely tau‐immunoreactive neuritic plaques (red arrows), making CTE evaluation more complicated in cases with high Alzheimer's disease burden (C) than cases with lower Alzheimer's disease burden (D). Other CTE cases may demonstrate more subtle neuropathology yet harbor all the required components of the consensus criteria (two cases; E,F). Finally, some cases show focal and patchy tau pathology reminiscent of CTE and inconsistent of other tauopathies, yet do not meet all consensus criteria (two cases; G,H). Possibly attributable to very early pathogenesis or limited restrictive sampling, “features of CTE” delineates high probability for pathological CTE yet not in accordance with all CTE consensus standards. Black bar: 500 μm, gray bar: 25 μm.

Figure 3

Proportion of males with combined CTE pathology in individuals who did not play football (white bars), who played youth or high school football only (blue bars), or who played football beyond high school (red bars) in the overall group and also in subgroups based on other sports played.