Most traumatic brain injury (TBI) research has focused on acute and moderate-to-severe illness. Now researchers affiliated with Centers for Disease Control and Prevention (CDC), Salt Lake City Veterans Administration, the University of Utah, the University of California San Francisco, and Cohen Veterans Bioscience (CVB) recommend that key stakeholders turn their attention to mild TBI and identifying how differences in population characteristics could influence the long-term consequences of TBI.

Authored by leading experts in the TBI field, this paper is the second in a six-part series resulting from the National TBI Precision Solutions Research Roadmap. The paper lays the framework for a consensus roadmap that points to actionable research priorities, leading to more targeted care based on population differences. The series is being published in the Journal of Neurotrauma.

As a direct outcome of the collaboration through the Brain Trauma Blueprint, CVB and its partners have identified critical population characteristics needing more thorough investigation across studies to predict who is at risk for developing persistent symptoms after a TBI. The work will also enhance understanding of how TBI can increase the risk of developing other neurological conditions, such as Alzheimer’s disease, other dementias and neurodegenerative conditions.

“It is imperative that we understand how different epidemiological factors influence the long-term consequences and reveal who might be at risk for developing neurological and neuropsychiatric disorders after a TBI of any severity,” said Nicole Harmon, PhD, Executive Director of External Affairs at CVB, Program Lead of the Brain Trauma Blueprint and a co-author on the paper.

According to the authors, there is significant heterogeneity in TBI: factors associated with poorer outcomes not only involving the extent and severity of the injury, but also epidemiological factors such as age, race, sex, co-existing conditions, and environment.

This report highlights the need to break down research barriers by encouraging collaborative efforts, including improvements in data collection, such as an expanded concussion surveillance system to assess prevalence in community-based populations, and a national registry that captures richer epidemiologic and other disease data. Furthermore, this report delivers a call to action for funders and collaborators across the broader stakeholder community to engage in longitudinal studies to enhance our understanding of the course and outcomes of TBI.

“Traumatic brain injury of all severities affects children and adults across the lifespan. It is not just an event, but a health condition that is impacted by co-existing conditions, particularly psychiatric and neurologic conditions,” said Juliet Haarbauer-Krupa, PhD, a senior health scientist on the TBI Team in the Division of Injury Prevention at CDC’s Injury Center, and the lead author of the paper. “By identifying factors that contribute to the chronic effects of TBI, we can guide clinicians toward more precise patient diagnosis with tailored management practices as well as inform research on long-term issues.”

The Brain Trauma Blueprint

The Brain Trauma Blueprint is a framework that enables stakeholder groups across government, academia, foundations, and industry to advance precision diagnostics and treatments for brain trauma through a coordinated effort. The framework comprises a 12-step process to jointly identify unmet patient needs, associated research priorities, landscape state of the science, identify research gaps and barriers, and provide recommendations for progress. The framework also provides a call to action for funders and collaborators across the broader stakeholder community to engage in a transparent and coordinated network.

Advancing TBI Care Through a Research Roadmap

Authored by leading experts in the traumatic brain injury field, the six-part series being published in the Journal of Neurotrauma will lay the framework for a roadmap to advance the field, based on a State-of-the-Science consensus conference held in 2019 with >125 leaders in the field.

Toward a Personalized Approach to TBI Care

TBI is a leading cause of disability in the U.S. Although most individuals who experience a TBI recover, a significant subset have persistent symptoms, including mental health conditions, sleep disturbances and memory impairment. Further increasing the personal and economic burden, many individuals, even those experiencing mild injuries, go on to develop neurological disorders including Alzheimer’s disease and other dementias. Despite the personal, economic, and societal costs of TBI, as well as the significant research investments, to date, there are no FDA-approved treatments that address the long-term consequences many individuals who have sustained a TBI will go on to develop. Many researchers believe that identifying critical population characteristics about who might go on to develop long-lasting symptoms or who might be susceptible to neurological disorders could be critical for the development of tailored treatment options.

Additional authors of the paper, titled Epidemiology of Chronic Effects of Traumatic Brain Injury [DOI: https://doi.org/10.1089/neu.2021.0062], include Mary Jo Pugh, PhD, professor in the Department of Medicine, Division of Epidemiology at the University of Utah School of Medicine and Investigator at the Informatics, Decision-Enhancement and Analytic Science Center of Innovation at the VA Salt Lake City; Eric M Prager, PhD; Nicole Harmon, PhD; Jessica Wolfe, PhD, MPH (Cohen Veterans Bioscience); and Kristine C. Yaffe, MD (UCSF).

Other publications in the series will cover additional key domains identified as barriers to progress: basic research, biomarker discovery and validation, clinical trial design, and clinical guideline implementation. Altogether, the TBI Precision Solutions Roadmap will guide the development of actionable research priorities that frame the next phase of the roadmap over the coming months.