A magnetic resonance spectroscopy investigation in symptomatic former NFL players

Abstract

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.

Keywords: Chronic traumatic encephalopathy; Magnetic resonance imaging; Magnetic resonance spectroscopy; Repetitive head impacts; Tackle football.

Fig. 1

Representative Voxel Locations and Spectra. (A) Voxel location (sagittal and axial, respectively) and spectra for the anterior cingulate gyrus, (B) Voxel location (sagittal and axial, respectively) and spectra for the posterior cingulate gyrus, (C) Voxel location (sagittal and axial, respectively) and spectra for the parietal white matter. Former NFL players were required to be symptomatic and “Controls” were individuals who were asymptomatic and did not have a history of head trauma.

Fig 2

Greater Exposure to Repetitive Head Impacts is Associated with Lower Later-life Parietal White Matter Creatine Concentrations. The scatter plot is of the residuals between the cumulative head impact index (CHII) and Creatine (Cr) after controlling for age and body mass index. X-axis represent each participant’s CHII, with higher scores reflecting greater exposure to RHI. Y-axis values are Cr concentrations. Shaded region is the 95% confidence intervals. The results remain unchanged when the individual with very low Cr concentrations was removed from the analysis.

Fig 3.

Association between Anterior Cingulate Gyrus Neurochemistry and Behavioral/Mood Symptoms. The scatter plots are of the residuals between the anterior cingulate gyrus (ACG) glutamate (glu), glutathione (GSH), and myo-inositol (mI) concentrations and the behavioral/mood principal component composite score after controlling for age, body mass index, and education. Higher concentrations of Glu (A), GSH (B), and mI (C) were associated with higher (i.e., worse) behavioral/mood scores. The x-axis is the neurochemical concentrations and the y-axis is the behavioral/mood composite scores. Shaded region represents 95% CI.