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National Football League (NFL) players are over three times more likely to be diagnosed with and die from amyotrophic lateral sclerosis (ALS) compared with the general U.S. male population, according to a cohort study.

Among over 19,000 former and current NFL players, 38 were diagnosed with ALS and 28 died over a mean follow-up of 30.6 years, reported Daniel Daneshvar, MD, PhD, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues in .

After adjusting for age and race, there was 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 male general population.

In addition, they found that an ALS diagnosis was more likely the longer athletes played in the league.

Nested case-control analyses found that players diagnosed with ALS had significantly longer careers, with a mean duration of 7 years, versus athletes without ALS, who had a mean career duration of 4.5 years (OR 1.2, 95% CI 1.1-1.3, P≤0.001).

This is the first study to examine ALS incidence among NFL players and the most comprehensive study of NFL players and ALS, the researchers said.

"The present study is also the first, to our knowledge, to show that greater duration of NFL play is associated with increased ALS rates among NFL athletes," they wrote.

Daneshvar and colleagues examined all 19,423 players (ages 23 to 78) who played in at least one game between 1960 and 2019.

They used a database maintained by Hidden Game Sports/24-7 Baseball to extract information on players. Ages at ALS diagnosis and death were obtained through public news reports and Legacy.com, and diagnoses of ALS at death were matched to National Death Index records.

Among those who were diagnosed with ALS and died, the average age at diagnosis was 52.5, and they lived with ALS for a mean of 3.5 years.

The researchers found no differences between athletes with ALS and those without ALS in debut BMI, race, Pro Bowl status, number of NFL Pro Bowl appearances, NFL Hall of Fame status, position, or location of birth.

Due to a lack of clinical information, the study could not assess clinical differences between groups, or other risk factors, such as family history, genetics, environmental toxin exposure, or lifestyle factors.

Daneshvar and colleagues postulated that there may be a connection between repetitive head hits and ALS, noting that previous studies have shown links between playing professional football and neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), which may be linked to ALS.

"This study tells us one mechanism for ALS may be repeated head hits," Daneshvar told 番茄社区. "Your brain doesn't care what hits it."

He said that he is concerned about the dearth of data on potential links between ALS and playing lower levels of football, including college and youth football. While pro football features more violent head hits with its bigger, faster, and stronger athletes, lower levels also have about the same amount of head contact per minute of play.

Daneshvar's team is currently looking at neurodegenerative diseases within people who played only lower levels of football.

In addition, people in combat, victims of domestic violence, and others known to suffer more head impacts may also be at a higher risk of ALS, he noted.

The 38 confirmed ALS cases is likely lower than the actual tally, Daneshvar said, noting that his team only reported on players who have publicly disclosed a diagnosis. In addition, many players who have debuted over the last generation are still younger than 60; thus, it is possible that some players from this cohort may be diagnosed later. One player revealed an ALS diagnosis after the study was completed in mid-July.

Nevertheless, Daneshvar was surprised to find so many confirmed diagnoses, adding that he had expected to find closer to 10 based on previous studies.

The researchers could not find data on repeated head impacts and traumatic brain injury, both within and beyond football, which was a study limitation. In addition, "given the low number of ALS cases, the study was underpowered to detect smaller differences," they wrote.

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