White Matter Alterations Are Associated With Cognitive Dysfunction Decades After Moderate-to-Severe Traumatic Brain Injury and/or Posttraumatic Stress Disorder

Abstract

Background: Possible white matter (WM) alterations following moderate-to-severe traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) and their relationship to clinical outcome have yet to be investigated decades after trauma. We utilized structural magnetic resonance imaging and diffusion tensor images to investigate brain volume and WM alterations in Vietnam War veterans with moderate-to-severe TBI and/or PTSD examined 5 decades after trauma. Methods: Data from 160 veterans—history of moderate-to-severe TBI (n = 23), history of TBI+PTSD (n = 36), history of PTSD (n = 53), and control veterans (n = 48)—were obtained from the Department of Defense Alzheimer's Disease Neuroimaging Initiative database. Voxel-based morphometry and tract-based spatial statistics were used to investigate ongoing brain morphometry and WM abnormalities. The fractional anisotropy (FA) and mean diffusivity were then correlated with neuropsychological scores and amyloid deposition in the trauma groups. Results: Compared with control subjects, the three trauma groups showed gray matter atrophy, lower FA, and distinctly higher diffusivity in the major WM tracts, including the corpus callosum, external and internal capsules, cingulum, and inferior and superior longitudinal fasciculi. The FA and mean diffusivity correlated with cognitive deficits in the trauma groups. Furthermore, the FA in the cingulum correlated negatively with amyloid deposition in the posterior cingulate cortex of all three trauma groups. Conclusions: Diffusion tensor imaging detected WM abnormalities that correlated with the severity of present cognitive dysfunction and the degree of cortical amyloid deposition decades after moderate-to-severe TBI and/or PTSD. These results may hint that PTSD secondary to TBI may incur late cognitive sequalae and persistence of brain microstructure alterations.