Exposure to repetitive head impacts is associated with corpus callosum microstructure and plasma total tau in former professional american football players
Creators: name: Kochsiek, Janna
name: O'Donnell, Lauren J.
name: Zhang, Fan
name: Bonke, Elena M.
name: Sollmann, Nico
name: Tripodis, Yorghos
name: Wiegand, Tim L. T.
name: Kaufmann, David
name: Umminger, Lisa
name: Di Biase, Maria A.
name: Kaufmann, Elisabeth
name: Schultz, Vivian
name: Alosco, Michael L.
name: Martin, Brett M.
name: Lin, Alexander P.
name: Coleman, Michael J.
name: Rathi, Yogesh
name: Pasternak, Ofer
name: Bouix, Sylvain
name: Stern, Robert A.
name: Shenton, Martha E.
name: Koerte, Inga K.
Publisher: name: Universität Ulm
Year: 2021
Subjects: subject: Sport‐related brain injury
subject: diffusion MR imaging
subject: tractography
subject: neurodegeneration
subject: neuropsychological testing
subject: DDC 610 / Medicine &amp; health
subject: Brain Injuries
subject: Sports medicine
subject: Athletic injuries
subject: Chronic traumatic encephalopathy
subject: Diffusion magnetic resonance imaging
subject: Neuropsychological tests
subject: Schädel-Hirn-Trauma
subject: Sportverletzung
subject: Nervendegeneration
subject: Diffusionsgewichtete Magnetresonanztomografie
subject: Neuropsychologischer Test

description: Background Exposure to repetitive head impacts (RHI) is associated with an increased risk of later‐life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. Purpose To investigate whether RHI exposure is associated with later‐life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. Study Type Retrospective cohort study. Population Seventy‐five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. Field Strength/Sequence Diffusion‐weighted echo‐planar MRI at 3 T. Assessment Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self‐report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free‐water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1‐7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT‐A) and Part B (TMT‐B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF‐A). Statistical Tests Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. Results RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P &lt; 0.05) and with increased plasma total tau (r = 0.34, P &lt; 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P &lt; 0.05; CC2: r = 0.29, P &lt; 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P &lt; 0.05) in TMT‐A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT‐B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P &lt; 0.05) in TMT‐A (FA, r = 0.36; AD, r = 0.28), TMT‐B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29). Data Conclusion These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players. Level of Evidence: 3 Technical Efficacy Stage: 1