Abstract

Abstract Objective Exposure to repetitive head impacts (RHI) has been linked to Chronic Traumatic Encephalopathy (CTE) and neuropathological alterations such as white matter shear injuries. In this study, we use diffusion-tensor imaging (DTI) to investigate in vivo white matter alterations among former American football players. We also investigate how age and factors associated with RHI exposure influence white matter integrity. Methods We analyzed data from the DIAGNOSE CTE Research Project, focusing on former American football players (n = 166). The measures included whole-brain Fractional Anisotropy (FA), reflecting water diffusion directionality in white matter, and FreeWater-corrected FA (FAt) accounting for extracellular free water, using FSL Tract-Based Spatial Statistics (TBSS). We performed linear regressions on FA and FAt with age, age of first exposure to football, and estimates of cumulative head impact index (CHII) scores of frequency, linear acceleration, and rotational force controlling for age, body mass index, race, education, and APOE e4 allele presence as covariates. Results Both FA (p < 0.00001) and FAt (p < 0.00001) decreased as age increased. Moreover, FA (p < 0.01) and FAt (p < 0.01) were significantly lower with an earlier age of first exposure to football. Finally, FAt decreased as CHII linear acceleration (p < 0.04) and rotational forces (p < 0.02) increased. Conclusion Our study reveals age-related declines in both FA and FAt and highlights that the duration and intensity of exposure to RHI have an impact on white matter microstructure later in life. Overall, these results underscore the impact of prolonged exposure to RHI on white matter microstructure.

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