In the Journals

New link established between football, brain damage

A significant proportion of brains donated by deceased football players for research showed neuropathological evidence of chronic trauma encephalopathy, according to research recently published in JAMA.

The research is the latest to suggest a link between chronic trauma encephalopathy (CTE) and playing football. A previous review of 66 brains at Mayo Clinic brain bank showed that 21 participants had pathology consistent with CTE, and of those, slightly more than half had played football.

In the present study, Jesse Mez, MD, MS, of Boston University’s Alzheimer’s and CTE Center, and colleagues analyzed 202 football players whose brains were donated for research into the effect of athletic behavior on neurodegenerative diseases, including CTE. Researchers assessed informant-reported athletic history and its relation to CTE neuropathological severity (mild [stages I and II] and severe [stages III and IV]), as well as clinical presentation, including behavior, mood, and cognitive symptoms and dementia for players who died in 2014 or later. The mean age of the participants at the time of death was 66 years old, and they had played football for an average of 15 years.

Mez and colleagues found that CTE was neuropathologically diagnosed in 177 of the 202 players, including included three of 14 high school players, 48 of 53 college players, nine of 14 semiprofessional players, seven of eight Canadian Football League players , and 110 of 111 National Football League players..

In addition, neuropathological severity of CTE was distributed across the highest level of play: three former high school players had mild pathology and the majority of former college (56%), semiprofessional (56%) and professional (86%) players having severe pathology. Among 27 participants with mild CTE pathology, 96% had behavioral or mood symptoms or both, 85% had cognitive symptoms, and 33% had signs of dementia. In the 84 participants who had severe CTE pathology, 89% had behavioral or mood symptoms or both, 95% had cognitive symptoms, and 85% had signs of dementia.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe. These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden,” Mez and colleagues wrote. “Several other football-related factors may influence CTE risk and disease severity, including but not limited to age at first exposure to football, duration of play, player position, cumulative hits, and linear and rotational acceleration of hits.”

In a related editorial, Gil D. Rabinovici, MD, of the University of California, San Francisco, noted that although this study represents the largest CTE cohort to date, there are still more questions than answers about the condition that need to be addressed.

“Fundamental questions about the disorder remain unresolved. What is the incidence and prevalence of CTE in population-based samples? What is the magnitude of risk associated with participating (and allowing children to participate) in various contact sports? Are there individual susceptibility and resilience factors that modify the risk or expression of the disease? What are the mechanisms that link acute [traumatic brain injury] to a latent neurodegenerative process, and what is the best way to intervene?” he wrote. “Addressing these questions will require improved disease models, and prospective studies in at-risk populations using an expanding armamentarium of biomarkers. Increased medical and public awareness around the diagnosis and prevention of [traumatic brain injury] remains paramount.”

Last year, the AMA implemented new policies that it hoped would lead to the creation of diagnostic tools and comprehension of preventive measures that can protect against CTE. Other research has suggested that rule or coaching changes to reduce head impact in player-to-player contact should be implemented to prevent greater head impact magnitude in high school football. – by Janel Miller

Disclosure: Mez reports no relevant financial disclosures. Rabinovici reports receiving research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare and Piramal; receiving consulting and/or speaking honoraria from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche and receives an honorarium for his duties as an associate editor of JAMA Neurology. Please see the study for a full list of the other authors’ relevant financial disclosures.

A significant proportion of brains donated by deceased football players for research showed neuropathological evidence of chronic trauma encephalopathy, according to research recently published in JAMA.

The research is the latest to suggest a link between chronic trauma encephalopathy (CTE) and playing football. A previous review of 66 brains at Mayo Clinic brain bank showed that 21 participants had pathology consistent with CTE, and of those, slightly more than half had played football.

In the present study, Jesse Mez, MD, MS, of Boston University’s Alzheimer’s and CTE Center, and colleagues analyzed 202 football players whose brains were donated for research into the effect of athletic behavior on neurodegenerative diseases, including CTE. Researchers assessed informant-reported athletic history and its relation to CTE neuropathological severity (mild [stages I and II] and severe [stages III and IV]), as well as clinical presentation, including behavior, mood, and cognitive symptoms and dementia for players who died in 2014 or later. The mean age of the participants at the time of death was 66 years old, and they had played football for an average of 15 years.

Mez and colleagues found that CTE was neuropathologically diagnosed in 177 of the 202 players, including included three of 14 high school players, 48 of 53 college players, nine of 14 semiprofessional players, seven of eight Canadian Football League players , and 110 of 111 National Football League players..

In addition, neuropathological severity of CTE was distributed across the highest level of play: three former high school players had mild pathology and the majority of former college (56%), semiprofessional (56%) and professional (86%) players having severe pathology. Among 27 participants with mild CTE pathology, 96% had behavioral or mood symptoms or both, 85% had cognitive symptoms, and 33% had signs of dementia. In the 84 participants who had severe CTE pathology, 89% had behavioral or mood symptoms or both, 95% had cognitive symptoms, and 85% had signs of dementia.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe. These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden,” Mez and colleagues wrote. “Several other football-related factors may influence CTE risk and disease severity, including but not limited to age at first exposure to football, duration of play, player position, cumulative hits, and linear and rotational acceleration of hits.”

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In a related editorial, Gil D. Rabinovici, MD, of the University of California, San Francisco, noted that although this study represents the largest CTE cohort to date, there are still more questions than answers about the condition that need to be addressed.

“Fundamental questions about the disorder remain unresolved. What is the incidence and prevalence of CTE in population-based samples? What is the magnitude of risk associated with participating (and allowing children to participate) in various contact sports? Are there individual susceptibility and resilience factors that modify the risk or expression of the disease? What are the mechanisms that link acute [traumatic brain injury] to a latent neurodegenerative process, and what is the best way to intervene?” he wrote. “Addressing these questions will require improved disease models, and prospective studies in at-risk populations using an expanding armamentarium of biomarkers. Increased medical and public awareness around the diagnosis and prevention of [traumatic brain injury] remains paramount.”

Last year, the AMA implemented new policies that it hoped would lead to the creation of diagnostic tools and comprehension of preventive measures that can protect against CTE. Other research has suggested that rule or coaching changes to reduce head impact in player-to-player contact should be implemented to prevent greater head impact magnitude in high school football. – by Janel Miller

Disclosure: Mez reports no relevant financial disclosures. Rabinovici reports receiving research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare and Piramal; receiving consulting and/or speaking honoraria from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche and receives an honorarium for his duties as an associate editor of JAMA Neurology. Please see the study for a full list of the other authors’ relevant financial disclosures.