BRAIN Health Project 4: Prognostic Screening for Poor BRAIN Health Outcomes following rmTBI and RHI

Traumatic brain injury (TBI) has been referred to as a “signature injury” of modern warfare. Significant advances have been made in the assessment, management, and rehabilitation of TBI in the military population over the last two decades. However, while a vast majority of service members with mild TBI (mTBI) recover within two weeks, the potential long-term impact of repetitive mTBI (rmTBI) remains unknown.

Limited research to guide military and public health efforts

Research in this area is equivocal, with some suggesting rmTBI has long-term behavioral, cognitive, neuromotor, and psychological health consequences and other evidence demonstrating that rmTBI is not associated with worse outcomes if managed appropriately post-injury.

Another concern is the potential long-term consequences of repetitive head impacts (RHI), such as those obtained during military occupational specialty (MOS) training for Tier 1 weapons systems. Research in this area is also limited and equivocal. For example, researchers have shown acute MOS training exposure linked to RHI has negative health outcomes, including tinnitus and persistent post-concussion symptoms. Recently, researchers have also suggested that long-term deficits assumed to be related to RHI were more likely associated with prolonged history of depression, anger, substance abuse, and/or exposure to adverse childhood experiences.

Given the limited research and ambiguous findings related to rmTBI and RHI’s potential long-term effects, it would be useful to military leadership and to public health if rmTBI is distinguishable from RHI regarding long-term health consequences. Objective biomarkers associated with rmTBI and RHI would also provide critical information regarding long-term health for individual service members.

A study to inform the field and guide treatment

In this effort, STRONG STAR is supporting the current project, which is one of a group of separate but related studies led by Anthony Kontos, PhD, of the University of Pittsburgh called “Brain Risk Assessment for Individual Neurological (BRAIN) Health: Understanding/Preventing Consequences From Repetitive mTBI and Head Impact Exposures,” which seeks to inform the field on the unique contribution of different levels of mTBI exposure along with biological risk factors on BRAIN health outcomes.

This particular project aims to evaluate a biologic signature of blood-based biomarkers, multidomain clinical markers, and individual demographic and medical history risk factors for the identification of service members who are at risk for reduced BRAIN health during a 12-month period following rmTBI and MOS-related RHI exposure.  Specifically, investigators will evaluate 100 service members representing two exposure groups: (1) 50 service members who have experience 3 or more rmTBIs and (2) 50 service members who have had 3 or more years of RHI exposure to Tier 1 weapons systems.

Participants will be assessed at enrollment and again 12 months later at military sites including Joint Base Lewis-McChord in Washington and Fort Hood in Texas. Participants will complete demographic and medical histories as well as clinical assessments of cognitive, behavioral, and neuromotor domains. They also will provide blood samples at enrollment and 12 months later.

Researchers will quantify the length and frequency of exposure to RHI from training and combat. They also will control for the number of rmTBI and time since last injury for the rmTBI group. All of this will be evaluated along with participants’ changes in chronic migraine, dizziness, neurocognitive symptoms, posttraumatic headache, psychological health, and sleep, as well as mild cognitive impairment and traumatic encephalopathy syndrome adjudication.

What researchers expect to learn and how it will help

At the project’s conclusion, researchers will have identified service members with rmTBI and RHI exposures who are at-risk for mild cognitive impairment with potentially progressive characteristics a year later. In so doing, the project will make a meaningful contribution to the overarching challenge that BRAIN Health aims to address, which is whether service members with poor prognosis from rmTBI or RHI can be distinguished from those with favorable prognosis using clinically feasible risk factor and clinical information, as well as objective biological markers.

Identifying an accurate set of variables for mild cognitive impairment can provide potential therapeutic targets to mitigate long-term consequences of rmTBI and RHI. If successful, this research effort will result in a timely and feasible prognostic screening approach involving combined demographic, medical history, clinical, and blood-based biomarkers to identify at-risk military service members for mild cognitive impairment following exposure to rmTBI and RHI.

The expected outcome from the exploratory blood-based biomarker evaluation is to provide a brief, objective, point-of-care assessment of key markers of brain health that can be readily applied in a variety of military medical, training, and operational environments. Such an approach may help provide objective evidence to identify at-risk service members and evaluate the pathophysiological effects of rmTBI and RHI exposures in SMs.