Summary: Researchers are launching a long-term study to track U.S. service members and veterans with mild traumatic brain injury (mTBI) for up to 20 years to document neurological outcomes and related deployment health issues.
Source: Veterans Affairs Research Communications.
Study will be one of the most comprehensive to date on TBI
The U.S. government has funded an ambitious long-term study enrolling at least 1,100 service members and veterans who served in Iraq or Afghanistan to improve understanding of mild traumatic brain injury (mTBI). The study aims to determine how best to evaluate, prevent, and treat mTBI and to identify potential long-term neurological consequences.
Although continued funding is not guaranteed, investigators plan to follow participants for 20 years or more. This extended follow-up is intended to capture late-life neurodegenerative conditions and other chronic effects that may emerge long after the initial injury.
The research team recently published the initial study design and early participant characteristics in the journal Brain Injury. More than 700 volunteers are already enrolled. Roughly 80 percent of participants report at least one prior mild TBI, while the remainder have no history of TBI. By comparing these groups, researchers hope to clarify how mTBI exposure relates to later outcomes. Individuals with moderate or severe TBI are excluded so the study concentrates exclusively on mild injuries.
This effort is coordinated by the Chronic Effects of Neurotrauma Consortium (CENC), one of two consortia established under the National Research Action Plan in 2013. The two consortia together received significant federal support and bring together investigators from the Departments of Veterans Affairs and Defense, other federal agencies, and academic institutions to study deployment-related brain injury and post-traumatic stress.
Dr. William Walker, a TBI specialist at the Richmond VA Medical Center and Virginia Commonwealth University, leads the CENC observational cohort. He describes the study as one of the largest and most rigorously designed efforts to examine the chronic effects of mild TBI to date.
At enrollment, each participant completes an intensive, standardized life-history interview focused on head injuries. The interview documents every possible concussive event across the participant’s lifetime—not only injuries that occurred during deployment, but also prior childhood incidents, civilian automobile accidents, sports-related blows, or incidents after military service.
“The cornerstone of this study is a detailed, standardized interview that maps lifetime head-impact exposures,” says Dr. Walker. “Many participants have experienced multiple concussions at various stages of life. We catalog each event and apply diagnostic criteria to determine whether it qualifies as a TBI.”
In addition to the interview, participants undergo a comprehensive battery of tests: neuroimaging, eye-movement tracking, computerized balance and vestibular assessments, neuropsychological testing, blood biomarker analysis, and other neurologic and sensory evaluations. The initial clinic visit typically lasts about eight hours. Follow-up plans include in-person comprehensive testing at least every five years combined with annual 45-minute telephone assessments to track cognition, memory, attention, and other symptoms between visits. Regular contact supports participant retention and provides richer longitudinal data.
Enrollment currently involves four VA sites—Richmond, Tampa, San Antonio, and Houston—and one Defense site, the National Center for the Intrepid at Fort Belvoir. Additional VA sites planned to begin enrollment include Boston, Minneapolis, and Portland.
Data from prior conflicts indicate that nearly 20 percent of the roughly 2.5 million service members and veterans who deployed to Iraq and Afghanistan since 2003 sustained at least one TBI, the majority being mild. Clinicians and researchers are finding additional undocumented mild TBIs as they screen veterans more thoroughly. Most mTBI cases resolve within weeks or months without lasting effects, but some individuals experience persistent cognitive, mood, sensory, or functional symptoms. Concerns include long-term deficits in thinking, memory, mood regulation, headaches, vision and hearing problems, and the possibility that mTBI increases risk for earlier onset neurodegenerative disease such as Alzheimer’s or chronic traumatic encephalopathy (CTE).
One primary research aim is to assess how the injury circumstances influence outcomes. For example: Are blast-related TBIs more harmful than blunt-force injuries? Do multiple TBIs produce different long-term effects than single events? The study will “fine slice” mTBI by classifying injuries as higher or lower grade based on initial symptoms, and the large, diverse sample should enable analyses across these subgroups.
Investigators will also examine biological risk and resilience factors. For instance, does carrying the APOE ε4 (APO E4) genetic variant—known to increase Alzheimer’s disease risk—heighten the long-term consequences of mTBI? Will measurable changes in cortical thickness, white-matter integrity, electrophysiology, or blood biomarkers predict cognitive decline or other adverse outcomes?
Dr. Walker emphasizes the need for extended follow-up to capture neurodegenerative conditions that typically appear later in life. “To estimate the incidence of conditions such as CTE, we believe a minimum of 20 years of follow-up is necessary,” he says. “If resources and participant survival allow, we plan to continue monitoring members of the cohort well beyond that timeframe.”
Funding: Supported by the U.S. Department of Veterans Affairs and the U.S. Department of Defense.
Source: Stephen Herring — Veterans Affairs Research Communications. Image credited to the U.S. Department of Defense.
Original research: Walker WC et al., “The Chronic Effects of Neurotrauma Consortium (CENC) multi-centre observational study: Description of study and characteristics of early participants,” Brain Injury. Published online November 11, 2016. DOI: 10.1080/02699052.2016.1219061
Abstract
The Chronic Effects of Neurotrauma Consortium (CENC) multi-centre observational study: Description of study and characteristics of early participants
Primary objectives: Establish and comprehensively assess a large cohort of U.S. veterans who served in recent conflicts to better understand chronic and late-life effects of mild traumatic brain injury (mTBI), including risks related to neurodegeneration.
Research design: Cross-sectional and prospective longitudinal study with planned long-term follow-up.
Methods and procedures: Eligibility requires prior combat deployment in Operation Enduring Freedom, Operation Iraqi Freedom, or related conflicts. The cohort spans the full spectrum of mTBI exposure, from no documented mTBIs to many. Longitudinal assessments include in-person comprehensive testing at least every five years with annual telephone evaluations. Primary outcomes focus on neuropsychological composite scores (NIH Toolbox), supported by structured interviews, standardized questionnaires, traditional neuropsychological batteries, motor and sensory testing, vestibular assessments, neuroimaging, electrophysiology, genotype analysis, and blood biomarkers.
Main outcomes and results: The study methods and measures are described in detail, and initial demographic and exposure characteristics of the early participant cohort are reported. The CENC observational study is underway and is expected to generate valuable longitudinal data for investigating the chronic effects of mTBI.