Players who spent at least five seasons battling it out in the National Football League (NFL) are three times more likely to die of a neurodegenerative disease than is the general population. Their risk for dying with dementia or amyotrophic lateral sclerosis hits fourfold. These sobering statistics appeared in the September 5 Neurology online. “Those are very high numbers,” said lead author Everett Lehman, National Institute for Occupational Safety and Health (NIOSH), Cincinnati, Ohio. “We conduct a lot of mortality studies, and we do not see such high risks very often,” he told Alzforum. (Uranium miners are one group that comes close.)
“The data support a notion that many of us have had: that playing a contact sport for a good chunk of your life at a high level is a risk for a variety of neurodegenerative disorders,” said Jeffrey Kutcher, University of Michigan, Ann Arbor. Kutcher did not participate in this study.
Growing evidence links sports-related head injuries, mostly concussions, to neurological problems and neurodegeneration later on in life (see ARF related news story). The medical field now recognizes chronic traumatic encephalopathy (CTE) as a major problem among football players, boxers, and other participants in contact sports. Against that backdrop, these new figures do not necessarily come as a huge surprise, said Lehman. Robert Cantu, Co-Director of the Center for the Study of Traumatic Encephalopathy at Boston University, agreed. “The BU center stores more than 100 donated brains, of which 30 are from deceased NFL players, and all had CTE,” Cantu told Alzforum. He was quick to point out that his may not be a representative sample, as the donations came predominantly from players who took their own lives or had severe problems later in life. “But we know CTE is out there, we just don’t know the prevalence and incidence,” he said.
Lehman and colleagues tried to address that issue in what Cantu considered pioneering work. The NIOSH researchers focused on more than 3,400 football professionals who played in the NFL between 1959 and 1988. Lehman followed them through 2007, documenting mortality. By then, 334 of them had died at an average age of 54. The good news is that, overall, the NFL retirees were half as likely to die during this period as were members of the general population. “As you can imagine, these are very fit individuals who received excellent medical attention,” said Lehman. Alas, how they died told another story. On standard death certificates, neurodegenerative disease, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS), turned up three times as often as underlying and contributing causes of death as it did for non-players. Narrowing that down, deaths related to dementia/AD and ALS were 3.86- and 4.31-fold higher, respectively. Both these diseases share pathologies found in CTE, including deposits of hyperphosphorylated tau and the RNA-binding protein TDP-43 (see ARF related news story). "Most of the existing data aimed at estimating the prevalence of major neurodegenerative diseases (AD, CTE, ALS) are postmortem and unavoidably biased. This study is unusual and important in the inclusion of ‘all-cause’ mortality data,” noted Sam Gandy, Mount Sinai Medical Center, New York, in an e-mail to Alzforum.
Other researchers contacted by Alzforum said that while these numbers are high, they are probably underestimates. Doctors often don’t record dementia as a contributing cause of death, especially in 50-year-olds, agreed Lehman (ARF related news story). Cantu noted that people with CTE can be asymptomatic for as long as 20 years, and without biopsy data a diagnosis of neurodegeneration may be missed. CTE was not even a recognized condition when many of these players passed away.
Underestimates or not, there are limitations to the study, as Lehman pointed out. Data on injuries and concussions were unavailable, and cause and effect cannot be established in this retrospective analysis. “We can presume impact led to these [mortality] rates being higher, but there are other variables to consider as well, including genetics and lifestyles that might put NFL players at risk, said Kutcher. A hint of the importance of impact comes from breaking down the data by player position. Defensive and offensive linemen fared best, being 1.6 times as likely as a non-NFL player to die of a neurodegenerative disease. That number jumped to 4.74 for players who tackle or are tackled at speed (including linebackers, running backs, quarterbacks, tight ends, and most other positions). The likelihood a physician noted dementia/AD or ALS on a “speed” position player’s death certificate was sixfold higher than normal.
"An important follow-up to this study would be to hunt for identifiable familial/genetic risk alleles that might enable the prospective prediction of those at highest risk," wrote Gandy. He noted that the increase in risk in the NFL players is roughly equivalent to that associated with a single ApoE4 allele, but that the combination of an ApoE4 allele and a serious traumatic brain injury with loss of consciousness could increase the risk for AD by 10-fold.
What do these data mean for the NFL? League spokesperson Greg Aiello sent Alzforum a prepared statement (see below) that outlined recent steps the league has taken to reduce player injuries. They include new rules that penalize for helmet-to-helmet contact. The league has also invested in research and care. Though the NFL dragged its heels in recognizing the seriousness of head trauma in years past (see ARF related news story), researchers now see signs that it is moving in the right direction. “I think since 2010, no other organization, professional or amateur, has done even a fraction of the amount of good toward protecting its participants with regard to head trauma as the NFL,” said Cantu. Kutcher agreed that the changes implemented by the NFL will help. “The big question is whether we can quantify that,” he said. “Where it will end up, we don’t know,” said Cantu, “but I don’t believe they can ever make [football] completely safe.”—Tom Fagan