Project Summary/Abstract – PI: C. Mac Donald – EVOLVE-10 Study The long-term clinical impact of war-time injuries remains incompletely described1,2. Previous studies have been based largely on self-report and screening tools3-6 to define TBI, rather than direct clinical assessments in cohorts identified at the time of injury and prospectively studied. As part of our prior efforts, we have successfully completed prospective, observational, longitudinal studies enrolling active-duty US military directly in the combat theatre in Afghanistan and following medical evacuation to Landstuhl, Germany at 0-7 days (median 4)17,18, 0-30 days (median 7-9)19,20, and 0-90 days (median 14)21-23 post-injury with evaluation at 1- year18-22 and 5-year24,25 outcome to date. We remain the only study to date that has prospectively followed active-duty US military from concussive brain injury directly in combat to long-term outcome with advanced MR imaging and clinical evaluation. We will leverage this well characterized cohort in the current proposal to investigate the long-term effects of mild-concussive traumatic brain injury (TBI) sustained during deployment in US military personnel using advanced MR imaging and clinical outcome measures. We will relate these findings to the prospectively acquired longitudinal imaging and clinical data from the acute, sub-acute, and early chronic stages following combat concussion collected on these subjects as part of our prior efforts. We hypothesize that combat concussion will differentially impact service members and that we will be able to identify those at high risk of continued decline verses those with a trajectory of recovery by leveraging the extensive early clinical and imaging data already collected in these very same patients linking it to the planned 10-year evaluation. Specific Aim #1: Assess 10-year neurological, neuropsychological, and psychiatric clinical outcomes of combat concussion in US military personnel leveraging previously acquired longitudinal data to identify predictors of long-term clinical outcome. Specific Aim #2: Examine 10-year advanced neuroimaging data in service members following combat concussion in US military personnel leveraging previously acquired longitudinal data to identify predictors of long-term imaging outcome. Specific Aim #3: Explore functional trajectories over this first decade post-injury using latent growth models to understand evolution or resolution of mental health symptoms, cognitive function, neurobehavioral symptoms and neuroimaging measures following combat concussion.

Project Narrative – PI: C. Mac Donald – EVOLVE-10 Study The overall goal is to investigate long-term advanced MR imaging measures and clinical outcome of concussive traumatic brain injury (TBI) sustained during deployment in US military personnel. We will relate these findings to prospectively acquired longitudinal imaging and clinical data from the acute/sub-acute, and early chronic stages following combat concussion collected on these patients as part of previous collaborative efforts. We hypothesize that early clinical and imaging measures can be used to predict high risk vs. low risk for poor 10-year outcome which will offer important insight into the long-term impact of war-time mild TBI thereby guiding new recommendations for clinical management and therapeutic intervention.