A magnetic resonance spectroscopy investigation in symptomatic former NFL players
The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = −0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.
KeywordsChronic traumatic encephalopathy Repetitive head impacts Magnetic resonance spectroscopy Magnetic resonance imaging Tackle football
This study was supported by grants from the NIH (P30 AG13846; R01 NS 078337; R56 9500304025; U01 NS093334). This publication was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through BU-CTSI Grant Number 1UL1TR001430. Michael L. Alosco, and research reported in this publication, was supported by the National Institutes of Health under grant number F32NS096803 and K23NS102399 and from a Pilot Grant from the Boston University Alzheimer’s Disease and CTE Center (P30AG13846). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Compliance with ethical standards
Conflict of interest
Robert C. Cantu is a paid consultant to the National Football League (NFL) Head Neck and Spine Committee and National Operating Committee on Standards for Athletic Equipment (NOCSAE), and is a paid member of the Medical Science Committee for the National Collegiate Athletic Association (NCAA) Student-Athlete Concussion Injury Litigation. He receives royalties from book publications, and compensation from expert legal opinion. Ann C. McKee has received funding from the NFL, World Wrestling Entertaintment (WWE), and is a member of the Mackey-White Committee of the NFL Players Association. Robert A. Stern has received research funding from Avid Radiopharmaceuticals, Inc. (Philadelphia, PA, USA). He is a member of the Mackey-White Committee of the NFL Players Association. He is a paid consultant to Biogen (Cambridge, MA) and Eli Lilly (Indianapolis, IN), and is a paid member of the Medical Science Committee for the NCAA Student-Athlete Concussion Injury Litigation. He receives royalties for published neuropsychological tests from Psychological Assessment Resources, Inc. (Lutz, FL). Alexander Lin was responsible for study concept and design, revising the manuscript, and analysis and interpretation of data. He is a paid consultant for Agios pharmaceuticals and Moncton MRI. He is also co-founder of Brainspec Inc. The remaining authors have no conflicts of interest to report. All authors have given final approval of the version to be published and agree to be accountable for the work.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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