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Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players

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Background and Objective

Despite being a postmortem diagnosis, former professional American-style football players report receiving chronic traumatic encephalopathy (CTE) diagnoses from medical care providers. However, many players also report other health conditions that manifest with cognitive and psychological symptoms. The purpose of this study was to identify how medical conditions, psychological disorders, and football exposure combinations are associated with former athletes reporting a premortem CTE diagnosis.


This study was a cross-sectional cohort survey from 2015 to 2019 of 4033 former professional American-style football players. Demographics (age, race, domestic status, primary care recipient), football-related factors (position, years of professional play, burden of symptoms following head impacts, performance-enhancing drug use), and comorbidities (sleep apnea, psychological disorder status [depression and anxiety; either depression or anxiety; neither depression nor anxiety], diabetes mellitus, attention-deficit/hyperactivity disorder, hypertension, heart conditions, high cholesterol, stroke, cancer, low testosterone, chronic pain, current and maximum body mass index) were recorded. A Chi-square automatic interaction detection (CHAID) decision tree model identified interactive effects between demographics, health conditions, and football exposures on the CTE diagnosis.


Depression showed the strongest univariate association with premortem CTE diagnoses (odds ratio [OR] = 9.5, 95% confidence interval [CI] 6.0–15.3). CHAID differentiated participants with premortem CTE diagnoses with 98.2% accuracy and area under the curve = 0.81. Participants reporting both depression and anxiety were more likely to have a CTE diagnosis compared with participants who reported no psychological disorders (OR = 12.2; 95% CI 7.3–21.1) or one psychological disorder (OR = 4.5; 95% CI 1.9–13.0). Sleep apnea was also associated with a CTE diagnosis amongst those with both depression and anxiety (OR = 2.7; 95% CI 1.4–5.2).


Clinical phenotypes including psychological disorders and sleep apnea were strongly associated with an increased likelihood of having received a pre-mortem CTE diagnosis in former professional football players. Depression, anxiety, and sleep apnea produce cognitive symptoms, are treatable conditions, and should be distinguished from neurodegenerative disease.

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Authors and Affiliations


Corresponding author

Correspondence to Shawn R. Eagle.

Ethics declarations


This work was supported by the Football Players Health Study at Harvard University, which is funded by the National Football League Players Association. The content is solely the responsibility of the authors, and does not necessarily represent the official views of Harvard Medical School, Harvard University, and its affiliated academic healthcare centers. The National Football League Players Association had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Conflict of interest

Ross Zafonte reported receiving royalties from Springer/Demos Publishing for serving as the coeditor of the text Brain Injury Medicine; serving on the scientific advisory board of Myomo Inc. and Inc.; evaluating patients in the Massachusetts General Hospital Brain and Body-TRUST Program, which is funded by the National Football League Players Association; and receiving grants from the National Institutes of Health. Aaron Baggish has received funding from the National Institutes of Health/National Heart, Lung, and Blood Institute, the National Football Players Association, and the American Heart Association and receives compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Marc G. Weisskopf reported receiving grants from the National Football League Players Association and the National Institutes of Health during the conduct of the study. Douglas P. Terry serves on the Scientific Advisory Board for HitIQ and previously consulted for REACT Neuro, Inc. Rachel Grashow and Heather DiGregorio received grant funding from the National Football League Players Association. Shawn R. Eagle has not conflicts of interest to disclose. David Okonkwo is the team neurosurgeon for the Pittsburgh Steelers football club.

Ethics approval

This study was approved by the Institutional Review Board of the Harvard T.H. Chan School of Public Health.

Consent to participate

Informed consent was provided by each participant.

Consent for Publication

Participants provided consent to publish study data.

Availability of data and material

Data may be available upon reasonable request to the Football Players’ Health Study.

Code availability

Not applicable.

Author contributions

SE and RG conceived of the study, conducted the statistical analyses, wrote the initial draft, revised the draft based upon feedback from collaborators, and submitted and approved the final draft. HD and DT contributed to the writing of the initial draft, critical revising of the draft, and approval of the final draft. AB, MW, and RZ contributed to the study design, critical review, and revising of the manuscript and approval of the final version. RZ also obtained the necessary study funding. DO contributed to the critical review, revision, and final approval of the manuscript.

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Eagle, S.R., Grashow, R., DiGregorio, H. et al. Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players. Sports Med (2023).

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