The proposed study is a cross-sectional and longitudinal, repeated measure, case-control multi- site study of Veterans with a history of OEF-OIF combat exposure. The purpose of this research is to examine the potential late-life effects of mTBI including possible neurodegenerative disorders such as CTE. The overall goals of this proposed large, longitudinal cohort study of Veterans with and without mTBI after OEF-OIF combat exposure are to (1) disentangle the role of mTBI(s) in their later life outcomes including but not limited to neurodegeneration, and (2) seek converging behavioral and biological evidence for CTE. The facilities engaged in recruiting and enrolling participants are McGuire VAMC in Richmond, James Haley VAMC in Tampa, South Texas Veterans Health Care System in San Antonio, and Michael DeBakey VAMC in Houston. To achieve these aims, all subjects will undergo an initial comprehensive assessment to determine the prevalence, type, and intensity of residual symptoms and impairments potentially attributable to TBI. Individuals with a history of TBI will be compared to controls with combat exposure and no history of TBI. All subjects will then undergo periodic (three years follow up and then every five years), in-person and annual telephonic reassessment to monitor the status of their condition and to assess for evidence of biologic, behavioral, cognitive, neurologic, and functional changes. In this way, the functional and biologic late effects of mTBI and their potential neurodegenerative decline over time will be delineated. In addition to descriptive statistics, the cross-sectional study will assess the association of mTBI and time from injury to current status while adjusting for multiple covariates including age and PTSD. The testing of differences between mTBI and controls will be powered by the primary outcome, cognitive function. Other outcome measures were assembled to measure all potential moderators of mTBI outcome and to track longitudinally the broad range of potential biologic markers, symptoms, impairments, comorbidities and disability known to be associated with TBI outcome and those purportedly linked to neurodegeneration. Physiologic, anatomic, and biologic tests posited to identify preclinical neurodegeneration will be conducted in parallel with cognitive testing; physical and sensory performance measures; and psychological, functional, disability, and global outcome measures. Criteria for participation This study of 1,100 combat-exposed OEF-OIF Veterans is expected to yield approximately 880 participants (80%) with at least one mTBI and 220 participants (20%) without any history of mTBI (referred to as controls). The inclusion criteria are (1) a history of OEF-OIF combat tour, and (2) a Combat Exposure Scale (CES) score > 1 on any item (light or higher). Thus, to ensure that cases and controls have similar environmental history, all participants will have exposure to stressful combat situations during OEF-OIF. All persons regardless of sex, race, or ethnicity will be included. Those with history of moderate or severe TBI, or other major neurologic disorder, will be excluded.

Public Health Relevance

This five year multi-center research program involves experienced brain injury scientists and doctors from Department of Veterans Affairs (VA), military, and university hospitals who will work together to better understand what happens to service members and veterans who get concussive injury to their brain during combat. Program researchers will try to figure out who is more likely to have problems after these injuries, how the injured can be better treated and cared for, and what the injured (and their families) can expect over their lifetime. This information will help service members and veterans who have had a brain injury, and their families, better understand what has happened to them, what they can do to feel better, and what they can expect as they get older. It will also help the professionals who provide care for service members and veterans better understand the problems that can occur and better ways to provide care. It will also help the VA and the military health systems provide the best possible care and the right benefits for service members and veterans who have these injuries. Pai-1

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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VA-DoD Consortium Projects - CENC (SPLF)
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VA Veterans Administration Hospital
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Cherry, Jonathan D; Mez, Jesse; Crary, John F et al. (2018) Variation in TMEM106B in chronic traumatic encephalopathy. Acta Neuropathol Commun 6:115
Cifu, David X; Diaz-Arrastia, Ramon; Williams, Rick L et al. (2015) The VA/DoD Chronic Effects of Neurotrauma Consortium: An Overview at Year 1. Fed Pract 32:44-48