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Key Points

Question  What are the neuropathological and clinical features of a case series of deceased players of American football neuropathologically diagnosed as having chronic traumatic encephalopathy (CTE)?

Findings  In a convenience sample of 202 deceased players of American football from a brain donation program, CTE was neuropathologically diagnosed in 177 players across all levels of play (87%), including 110 of 111 former National Football League players (99%).

Meaning  In a convenience sample of deceased players of American football, a high proportion showed pathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

Abstract

Importance  Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).

Objective  To determine the neuropathological and clinical features of deceased football players with CTE.

Design, Setting, and Participants  Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history.

Exposures  Participation in American football at any level of play.

Main Outcomes and Measures  Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia.

Results  Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia.

Conclusions and Relevance  In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

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Article Information

Corresponding Author: Ann C. McKee, MD, Neuropathology Service, VA Boston Healthcare System, CTE Center, Boston University Alzheimer’s Disease Center, Boston University School of Medicine, 150 S Huntington Ave, Boston, MA 02118 (amckee@bu.edu).

Accepted for Publication: June 20, 2017.

Author Contributions: Drs Mez and McKee had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Mez, Daneshvar, and Mr Kiernan are co–first authors.

Concept and design: Mez, Daneshvar, Abdolmohammadi, Murphy, Montenigro, Kowall, Cantu, Stern, McKee.

Acquisition, analysis, or interpretation of data: Mez, Daneshvar, Kiernan, Abdolmohammadi, Alvarez, Huber, Alosco, Solomon, Nowinski, McHale, Cormier, Kubilus, Martin, Murphy, Baugh, Montenigro, Chaisson, Tripodis, Weuve, McClean, Goldstein, Katz, Stern, Stein, McKee.

Drafting of the manuscript: Mez, Daneshvar, Abdolmohammadi, Alosco, Martin, Murphy, Montenigro, McKee.

Critical revision of the manuscript for important intellectual content: Mez, Daneshvar, Kiernan, Abdolmohammadi, Alvarez, Huber, Alosco, Solomon, Nowinski, McHale, Cormier, Kubilus, Baugh, Chaisson, Tripodis, Kowall, Weuve, McClean, Cantu, Goldstein, Katz, Stern, Stein, McKee.

Statistical analysis: Mez, Daneshvar, Abdolmohammadi, Huber, Montenigro, Tripodis, Weuve.

Obtained funding: Mez, Nowinski, McKee.

Administrative, technical, or material support: Daneshvar, Kiernan, Abdolmohammadi, Alvarez, Huber, Alosco, McHale, Cormier, Kubilus, Murphy, Baugh, Montenigro, Chaisson, Kowall, McClean, Stein, McKee.

Supervision: Mez, Daneshvar, Abdolmohammadi, Solomon, Cantu, Stern, McKee.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Nowinski reported that he receives travel reimbursements for various unpaid advisory roles from the NFL Players’ Association, Major League Lacrosse, World Wrestling Entertainment (WWE), National Collegiate Athletic Association (NCAA), and the Ivy League; receives royalties from the publication of his book Head Games: The Global Concussion Crisis, published by Head Games The Film; served as a consultant for MC10 Inc as recently as 2013; serves as chief executive officer of the Concussion Legacy Foundation; and receives speaking honoraria and travel reimbursements for educational lectures. Ms Baugh reported that she receives research funding through the NCAA and the Harvard Football Players Health Study, which is funded by the NFL Players’ Association. Dr Cantu reported that he receives compensation from the NFL as senior advisor to its Head, Neck and Spine Committee, from the National Operating Committee on Standards for Athletic Equipment as chair of its Scientific Advisory Committee and from the Concussion Legacy Foundation as cofounder and medical director for some talks given and receives royalties from Houghton Mifflin Harcourt and compensation from expert legal opinion. Dr Stern reported that he has received research funding from the NFL, the NFL Players’ Association, and Avid Radiopharmaceuticals Inc; is a member of the Mackey-White Committee of the NFL Players’ Association; is a paid consultant to Amarantus BioScience Holdings Inc, Avanir Pharmaceuticals Inc, and Biogen; and receives royalties for published neuropsychological tests from Psychological Assessment Resources Inc and compensation from expert legal opinion. Dr McKee reported that she has received funding from the NFL and WWE and is a member of the Mackey-White Committee of the NFL Players’ Association.

Funding/Support: This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL.

Role of the Funder/Sponsor: The funders of the study 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; or decision to submit for publication.

Additional Contributions: We acknowledge the use of the resources and facilities at VA Boston Healthcare System and the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, Massachusetts). We also acknowledge the help of all members of the CTE Center at Boston University School of Medicine, Concussion Legacy Foundation, and the individuals and families whose participation and contributions made this work possible.

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