PURPOSE:
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football.We hypothesized that, as duration of American football played increased, CTE neuropathological risk and severity would correspondingly increase. To account for selection bias, we adjusted for known predictors of selection into brain banks using inverse probability weighting (IPW); because of unique criteria, we also conducted simulation to further evaluate the effect of selection bias. METHODS: In a convenience sample of 266 deceased American football players from the VA-BU-CLF and Framingham Heart Study (FHS) Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. To be eligible the VA-BU-CLF Brain Bank, donors needed a history of CCS, military service, or domestic violence, regardless of whether symptoms manifested during life. All brains from either brain bank were processed and analyzed using identical methods. Neuropathologists were blinded to the participant’s CCS exposure and clinical history.RESULTS:
In models adjusted for age at death, there was a dose-response relationship between longer duration played with CTE status and severity; each additional year of play corresponded to 30% higher odds of having CTE at death (95%CI, 1.19‐1.41; P=3.8x10-9) and 14% higher odds of having severe CTE at death (95%CI, 1.07‐1.22; P=3.1x10‐4). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio [LR]=0.102, 95%CI, 0.100‐0.105) and were 10X as likely to have played >14.5 years (+LR=10.2, 95%CI, 9.8‐10.7). Simulation demonstrated that years played remained adversely associated with CTE status across all values of selection regression scenarios.
CONCLUSIONS:
Duration played was significantly associated with odds of CTE at death, with odds increasing 30% every year, doubling every 2.6 years and increasing by >10-fold every nine years. Among those with CTE, duration played also was also significantly associated with having severe CTE pathology and greater NFT burden. Duration played was a good classifier of CTE status based on ROC curve analysis.