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Observational Study
. 2021 Dec 1;4(12):e2138801.
doi: 10.1001/jamanetworkopen.2021.38801.

Incidence of and Mortality From Amyotrophic Lateral Sclerosis in National Football League Athletes

Daniel H Daneshvar  1   2   3   4 , Jesse Mez  4   5   6 , Michael L Alosco  4   5 , Zachary H Baucom  4   7 , Ian Mahar  4   5 , Christine M Baugh  8   9 , Jhaqueline P Valle  10 , Jennifer Weuve  11 , Sabrina Paganoni  1   2   3   12 , Robert C Cantu  4   5   13   14   15 , Ross D Zafonte  1   2   3   16 , Robert A Stern  4   5   13   17 , Thor D Stein  1   18   19   20 , Yorghos Tripodis  4   7 , Christopher J Nowinski  4   14 , Ann C McKee  4   5   6   18   19   20
Affiliations
Observational Study

Incidence of and Mortality From Amyotrophic Lateral Sclerosis in National Football League Athletes

Daniel H Daneshvar et al. JAMA Netw Open. .

Abstract

Importance: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; understanding ALS risk factors is a critical public health issue.

Objectives: To evaluate the incidence of and mortality from ALS in National Football League (NFL) athletes and to describe characteristics associated with ALS within this cohort.

Design, setting, and participants: This population-based cohort study included all 19 423 NFL athletes who debuted between 1960 and 2019 and played 1 or more professional game. It was conducted between October 3, 2020, and July 19, 2021.

Exposure: Participation in the NFL, including playing 1 or more professional games.

Main outcomes and measures: Cases of ALS and death information were identified based on public records from NFL statistics aggregators, news reports, obituaries, and National Death Index results. The standardized incidence ratio and the standardized mortality ratio were calculated based on data acquired from surveillance studies of ALS accounting for age, sex, and race. Secondary analyses examined the association of body mass index, NFL career duration, race, birth location, and markers of fame, using a nested case-control design, matching athletes with ALS to athletes without ALS, by NFL debut year.

Results: A total of 19 423 male former and current NFL players (age range, 23-78 years) were included in this cohort study and were followed up for a cumulative 493 168 years (mean [SD] follow-up, 30.6 [13.7] years). Thirty-eight players received a diagnosis of ALS, and 28 died during the study time frame, representing a significantly higher incidence of ALS diagnosis (standardized incidence ratio, 3.59; 95% CI, 2.58-4.93) and mortality (standardized mortality ratio, 3.94; 95% CI, 2.62-5.69) among NFL players compared with the US male population, adjusting for age and race. Among NFL athletes, nested-case-control analyses found that those who received a diagnosis of ALS had significantly longer careers (mean [SD] duration, 7.0 [3.9] years) than athletes without ALS (mean [SD] duration, 4.5 [3.6] years; odds ratio, 1.2; 95% CI, 1.1-1.3). There were no differences in ALS status based on proxies of NFL fame, body mass index, position played, birth location, or race.

Conclusions and relevance: The age-, sex-, and race-adjusted incidence of and mortality from ALS among all NFL players who debuted between 1960 and 2019 were nearly 4 times as high as those of the general population. Athletes with a diagnosis of ALS had longer NFL careers than those without ALS, suggesting an association between NFL duration of play and ALS. The identification of these risk factors for ALS helps to inform the study of pathophysiological mechanisms responsible for this fatal neurodegenerative disease.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mez reported receiving grants from the National Institutes of Health (NIH)/National Institute on Aging (NIA)/National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. Dr Alosco reported receiving royalties from Oxford University Press outside the submitted work; and grants from the NIH. Dr Baugh reported receiving grants from Datalys Center for Sports Injury Research and Prevention and personal fees from the University of Connecticut (funded by a grant from the National Football Leauge [NFL] Foundation) for serving as a consultant on a concussion legislation project with the University of Connecticut, outside the submitted work. Dr Paganoni reported receiving grants from Amylyx, Revalesio, Clene, Prilenia, UCB, Seelos, and Biohaven; and personal fees from Orion and Cytokinetics outside the submitted work. Dr Cantu reported serving as senior advisor to the NFL Head, Neck and Spine Committee; serving as vice president of National Operating Committee on Standards for Athletic Equipment and chair of the scientific advisory committee for National Operating Committee on Standards for Athletic Equipment; being co-founder and medical director of the Concussion Legacy Foundation; receiving royalties from Houghton Mifflin Harcourt; and providing legal expert opinion (eg, the National Collegiate Athletic Association [NCAA] and the National Hockey League). Dr Zafonte reported receiving royalties from Springer/Demos Publishing for serving as co-editor of the text Brain Injury Medicine; serving on the scientific advisory board of Myomo, and onecare.ai; and evaluating patients in the Massachusetts General Hospital Brain and Body-Trust Program, which is funded by the NFL Players Association. Dr Stern reported receiving grants from the NIH during the conduct of the study; personal fees from Biogen and Eli Lilly; and stock options as a member of the board of directors from King-Devick Technologies outside the submitted work; and is a member of Medical Science Committee of the NCAA Student-Athlete Concussion Injury Litigation and a member of the Mackey-White Health and Safety Committee, NFL Players Association; in addition, Dr Stern had a patent with royalties paid from Psychological Assessment Resources Inc for published neuropsychological tests. Dr Nowinski reported receiving travel support from the NFL Players Association; being a member of the NFL Players Association Mackey-White Health and Safety Committee; and holding options in Oxeia Biopharmaceuticals and PreCon Health outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Study Inclusion and Exclusion Criteria for National Football League (NFL) Cohort and Nested Case-Control Analyses
ALS indicates amyotrophic lateral sclerosis.
See this image and copyright information in PMC

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