Neurometabolic Alterations in Retired NFL Athletes

Abstract

PURPOSE: Repetitive brain trauma (RBT) places athletes at risk for chronic traumatic encephalopathy (CTE), a neurodegenerative disorder characterized by hyperphosphorylated tau protein. Not all those exposed to RBT will ultimately develop the disease, suggesting the importance of other factors such as the number of head impacts sustained throughout the career. American football athletes playing line positions are known to sustain more impacts per season than players in skill positions. We thus hypothesized neurometabolic differences reflective of traumatic brain injury between these groups of players compared to controls. METHODS: Magnetic resonance spectroscopy (MRS) was used to acquire metabolite concentrations in retired National Football League players (n=69) and age-matched controls (n=17) who were retired professional athletes from non-contact sports. Single voxel point-resolved spectroscopy (PRESS; TE=35ms, TR=2s, 2x2x2 cm3) and two-dimensional correlated spectroscopy (2D-COSY) was acquired from the posterior cingulate gyrus. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine (Cr), glutathione (GSH), choline-containing compounds (GPC+PCh), and myo-inositol (mI) were measured using an operatorindependent time domain based fitting of linear combination models (LCModel). Subjects were organized by position according to average number of head impacts sustained per season. Offensive and defensive lineman formed a “high risk” group, while running backs, defensive backs, and linebackers made up a “moderate risk” group. Linear regression analysis was performed for each position and metabolite of interest, and repeated measures one-way ANOVA with Tukey’s test was used to assess for neurometabolite differences between groups. RESULTS: A significantly higher concentration of Glu/Cr+PCr was observed in the high risk group compared to the moderate risk group (p=0.02), and concentrations of Glu/Cr+PCr by position played was positively correlated with average number of impacts sustained per season (p=0.007). There was also a significantly higher concentration of glutamate+glutamine (Glx-3) in the high risk group compared to both moderate risk (p=0.02) and controls (p=0.01). NFL players as a whole exhibited a significantly higher concentration of glutathione (GSH-1) (p=0.03) and a significantly lower concentration of choline containing compounds (GPC+PCh/Cr+PCr) compared to controls (p=0.008). CONCLUSIONS: Our results support a model of glutamatergic excitotoxicity and a possible oxidative stress response with chronic exposure to RBT. The decrease in choline-containing compounds with RBT exposure may reflect oligodendrocyte pathology, though further work is needed to replicate these findings.