In American football, using your head may mean different things to different players. A top-class quarterback like Peyton Manning uses it for millisecond analysis of the state of play, but for a running back or a lineman it often doubles as a battering ram. Not surprisingly, football players suffer their fair share of concussions, despite the helmets. Do these mild traumas have long-term effects? Some recent autopsy data may re-energize the debate over the link between repetitive brain injuries and subsequent neurological decline, including depression and the development of Alzheimer-like pathologies, such as amyloid plaques and neurofibrillary tangles.
In last month’s Neurosurgery, Bennet Omalu and colleagues from the University of Pittsburgh, Pennsylvania, report autopsy data on retired National Football League (NFL) offensive guard Terry Long, who committed suicide in November 2005 at age 45 following a long battle with depression. They write that Long had chronic traumatic encephalopathy (CTE) accompanied by widespread neurofibrillary tangles and neuropil threads in the brain. The findings are reminiscent of an earlier autopsy on another ex-Pittsburgh Steeler, “Iron” Mike Webster. Omalu and colleagues, including University of Pittsburgh’s Steve DeKosky, had reported in July of 2005 that the 50-year-old Webster also had had CTE along with many diffuse amyloid plaques in his brain and sparse neurofibrillary tangles (Omalu et al., 2005). That earlier paper found itself hotly challenged by members of the NFL’s Mild Traumatic Brain Injury Committee, who asked for its retraction. The Committee’s rationale was not that the data was incorrect, but that Omalu and colleagues misinterpreted the definition of chronic traumatic encephalopathy. As far as this reporter has determined, the committee has not yet commented on Omalu’s new paper. Nor has it issued an official response to a story in the 18 January New York Times reporting that Omalu found similar neuropathology in the brain of a third former NFL player, Philadelphia Eagles defensive back Andre Waters, who committed suicide in November of 2006 at the age of 44.
In a telephone interview with Alzforum, Omalu said that though Waters’s complete brain had not been saved after autopsy, sufficient material was saved for histochemical analysis on more than 120 sections. “We found frequent density of neurofibrillary tangles and neuritic threads in the hippocampus, the neocortex, and the brainstem,” said Omalu. If the findings stand up to peer review, this will represent the third young ex-NFL player to exhibit pathologies normally associated with 70- and 80-year-old AD patients.
Three retrospective cases are hardly proof that football-related injuries precipitate AD-like pathologies in the prime of life. For this reason, Omalu and colleagues have called for a prospective, longitudinal study on a specified cohort of former professional contact-sport players, such as the NFL Hall of Famers. A preponderance of evidence from other studies suggests that the effects of repetitive mild traumatic brain injuries are cumulative. Kevin Guskiewicz and colleagues at the University of North Carolina, Chapel Hill, reported that NFL players who have received three or more concussions during their careers are five times more likely to suffer from mild cognitive impairment (Guskiewicz et al., 2005). The issue is a sensitive one for other professional sports, as well, such as boxing (Jordan, 2000).
Within the NFL, part of the debate surrounds the question of how quickly a player should play again after sustaining a concussion, and what medical attention is appropriate to prevent long-term consequences. But many neurodegeneration researchers may question whether any medical intervention is available to stem a long-term process of pathology buildup triggered by repetitive mild head trauma. These researchers are less surprised by a link between such trauma and neurofibrillary/amyloid pathologies than by the fact that this is news to society at large. Animal studies have documented this connection repeatedly (e.g., Yoshiyama et al., 2005; Uryu et al., 2002), and human data exist, as well (e.g., Jellinger, 2004).
“Recently there has been a major shift in scientific thought about the long-term sequelae of playing football. What we are finding out is that these repetitive concussions are cumulative over time and additive, and when players retire many years later they may have dementia-like disease,” said Omalu. Where do AD researchers stand on this issue? Are you letting your kids play high school football?—Tom Fagan