Relationship Between Level of American Football Playing and Diagnosis of Chronic Traumatic Encephalopathy in a Selection Bias Analysis

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school-level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players' lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE.

Keywords: American football; autopsy; chronic traumatic encephalopathy; football; probabilistic analysis; repetitive head injury; selection bias.

Figure 1

Distributions of the probabilities of selection into the study, conditional on traumatic encephalopathy (CTE) status, exposure status (highest level of football playing), and death, for an analysis comparing collegiate American football players with high school football players, VA-BU-CLF Brain Bank, 2008–2019. A) P(S|D+, E2, Death) denotes the probability of selection conditional on CTE diagnosis and having played college football. B) P(S|D−, E2, Death) denotes the probability of selection conditional on no CTE diagnosis and having played college football. C) P(S|D+, E1, Death) denotes the probability of selection conditional on CTE diagnosis and having played high school football. D) P(S|D−, E1, Death) denotes the probability of selection conditional on no CTE diagnosis and having played high school football. VA-BU-CLF, Veterans Affairs–Boston University–Concussion Legacy Foundation.

Figure 2

Distributions of the probabilities of selection into the study, conditional on chronic traumatic encephalopathy (CTE) status, exposure status (highest level of football playing), and death, for an analysis comparing professional American football players with high school football players, VA-BU-CLF Brain Bank, 2008–2019. A) P(S|D+, E3, Death) denotes the probability of selection conditional on CTE diagnosis and having played professional football. B) P(S|D−, E3, Death) denotes the probability of selection conditional on no CTE diagnosis and having played professional football. C) P(S|D+, E1, Death) denotes the probability of selection conditional on CTE diagnosis and having played high school football. D) P(S|D−, E1, Death) denotes the probability of selection conditional on no CTE diagnosis and having played high school football. VA-BU-CLF, Veterans Affairs–Boston University–Concussion Legacy Foundation.