CENC0001C - Observational Study on Late Neurologic Effects of OEF/OIF/OND Combat

There are many effects of traumatic brain injury (TBI) that occur immediately after the injury, including cognitive and behavioral changes. These changes in function may be related to changes in brain structure that can be seen on MRI scans. There may also be impairments in fine motor skills, coordination and balance, visual perception, and language. All of these acute effects get better over time unless an injury is very severe, in which case the impairments persist indefinitely.

For less severe head injuries, known as mild TBI (mTBI) or concussion, the effects later in life are understudied and less understood. This lack of research needed to understand the long-term outlook, including the potential risk of worsening problems, specifically chronic traumatic encephalopathy (CTE), creates a critical problem for the care of the mTBI patient. Awareness of this problem has increased as more reports and retrospective case series suggest mid- and late-life risks from mTBI, especially multiple concussions. The potential for early dementia after mTBI(s) is a frightening prospect for Service members (SMs) and Veterans who have sustained mTBI(s) during their service to our country.

The purpose of this study is to address this critical research gap by identifying and characterizing the late effects of mTBI and assessing the influence and interaction of the many potential risk factors for early dementia. To achieve these goals, the CENC relies on the expertise and knowledge of multiple civilian and military research groups, including the National Institute for Disability and Rehabilitation Research (NIDRR) TBI Model System (TBIMS) program, which has studied the long-term outcomes of more than 10,000 people with moderate to severe TBI for the past 20 years. The CENC study will extend the work of the TBIMS program to the population of Veterans with mTBI using a mixed-methods approach of combining patient-reported outcomes with assessments of cognitive and neurologic functioning. The study will also look at biological measures including laboratory, neuroimaging, and electrophysiological testing to sort out the role of mTBI in late outcomes including CTE and other illnesses.

This study’s goal is to establish a large cohort (880) of former U.S. OEF/OIF/OND combatants who have had at least one mild Traumatic Brain Injury (mTBI) and follow the members of the cohort long-term to assess specific areas of their physical and mental health. Given the unclear role of mTBI(s) on long term health and the frequent co-occurrence of posttraumatic stress disorder (PTSD) in warfighters, the study will include a group of participants (220) who have experienced combat but have not had an mTBI.

All study participants will first have a detailed assessment to determine whether they have had an mTBI in the past and to assess the type, if any, of mental and physical health problems they are currently experiencing. After the first assessment, participants will have yearly re-assessments either over the phone or in person to follow up on the first set of measures.

The structured mTBI diagnostic interview instruments being used in this study were developed and tested in an earlier study by Walker et al [1] and are available to the public as free downloads below:

[1] Walker WC, Cifu DX, Hudak A, Goldberg G, Kunz RD, Sima A. Structured interview for mild traumatic brain injury after military blast: inter-rater agreement and development of a diagnostic algorithm. J Neurotrauma 2015; 32(7):464-73. PMID 25264909

At a Glance

Study type:

Observational Cohort Study


To identify and asses the long-term effects of mild TBI


Veterans and Service Members over 18 years of age with a history of OEF/OIF/OND deployment and combat exposure

Number of participants:

1,100 (880 mTBI exposed, 220 unexposed)

Data collection:

Data collected will include a variety of clinical measures, cognitive and neurological functioning assessments, patient-reported outcomes, biological measures including biospecimen, and MRI analysis

Participating sites:

Richmond VA, Tampa FL, Houston TX, San Antonio TX, Fort Belvoir VA, Portland OR, Boston MA, Minneapolis, MN

Principal investigator:

David Cifu, M.D., Virginia Commonwealth University

Study Chair:

William C. Walker M.D., Virginia Commonwealth University


Currently enrolling, duration TBD. Currently enrollment to stop 3/31/2018.