This study's overall goal is to establish a large, longitudinal cohort of former U.S. OEF/OIF/OND combatants, including those exposed and unexposed to mTBI(s), and measure their chronic sequelae and comorbidities. All subjects will undergo an initial comprehensive assessment to determine their TBI status along with the prevalence, type, and intensity of chronic sequelae from TBI and associated comorbidities. All subjects will undergo periodic in-person and telephone reassessment to monitor the status of the sequelae and comorbidities and to assess for evidence of neurologic (cognitive, behavioral, physical) decline.
Aim 1: Establish a large longitudinal mTBI exposed vs. unexposed cohort of OEF/OIF/OND era Veterans and SMs to comprehensively evaluate for the late effects of combat-related mTBI including evidence of neurodegeneration. 1A: Establish a registry of persons with combat exposure who were deployed in support of OEF/OIF/OND of whom a vast majority (target near 80%) sustained mTBI(s) as willing research participants to follow longitudinally and to offer future randomized clinical intervention trials and pathology studies. See section 5.5.2. ?Post-Consent mTBI diagnostic assessment? for methods used to meet the 80% target distribution of participants with mTBI(s). 1B: Validate the mTBI(s) history (absence versus presence; if present number, severity, date(s) and cause) of each participant and establish an index date for timing their reassessments. 1C: Collect data on all potential non-TBI confounders and moderators of outcome, including premorbid cognition, prior medical and psychological health, intensity of combat experience, social support, PTSD, self-efficacy, resilience, symptom exaggeration, sleep, and pain. Aim 2: Determine whether the mTBI exposed group differs from the non-TBI control group and the effects of single versus multiple mTBIs either on baseline post-acute outcomes or longitudinally across time (adjusting for potential moderators including personal factors, environmental factors, and comorbidities). Outcomes include: 2A: A comprehensive battery of both traditional and emerging state-of-the-art neurocognitive measures. 2B: A comprehensive battery of motor, sensory, neurologic, and psychological outcomes. 2C: Occupational and social functioning measures, including disability and global health outcomes. 2D: Health services utilization and costs and quality adjusted life-years (QALYS) Aim 3: Identify subgroups with different levels or patterns of decline over time inferring neurodegeneration. Subgroups will be potentially defined by moderating factors and a variety of clinical variables (baseline neurocognitive, neurological signs and symptoms). The a priori patterns of main interest are purported behavioral pattern(s) of CTE; that is: Stage 1: poor concentration and headaches Stage 2: memory problems, depression, poor impulse control, and emotional instability Stage 3: executive dysfunction, cognitive impairment Stage 4: language difficulties, aggression, and dementia. Aim 4: Identify biologic variables (for example: APO E4 carrier, other genotype, cortical thickness changes, disrupted white matter integrity, white matter hyperintensities, altered cerebral blood flow, disrupted functional connectivity, neuroendocrine abnormality, presence or absence of pathology) associated with Aim 3 patterns to provide converging evidence for neurodegeneration. Aim 5 (Exploratory, Richmond only): Measure ERPs (specifically multimodal working memory, long-term memory access, & auditory cortical potentials) to: 5A. Seek additional physiologic evidence of neurodegeneration via association to Aim 3 patterns. 5B. Clarify functional significance of changes in neurobiological variables through real-time measure of neural coordination. 5C. Characterize the neurocognitive mechanisms of impairments shown on cognitive performance tests.