Research & Clinical Trials

Concussion Research Priorities

1. Understanding the Effects of Multiple Concussions.

Athletes, parents, coaches, athletic trainers, physicians, scientists, and society as a whole are concerned about the possible effects of multiple concussions on adolescents and young adults. We will rapidly pursue the largest research program to date on the effects of multiple concussions in adolescent student athletes. In collaboration with Colby College and the Maine Concussion Management Initiative, we now have a database of approximately 45,000 adolescent athletes who underwent baseline preseason cognitive testing. Thousands of these athletes have a history of prior concussions. We also have a database of approximately 6,000 student athletes who have sustained a concussion and have completed cognitive testing immediately following their injuries. With this research program, we will systematically address the questions listed below. Importantly, all of these research questions can be addressed with data that has already been collected in Maine.

a. Are athletes who have had prior concussions at increased risk for future concussions?

b. Do athletes with multiple past concussions have worse effects of a future concussion than athletes who have no prior injuries?

c. Are athletes with developmental problems, such as attention-deficit hyperactivity disorder (ADHD) or a learning disability, at increased risk for (a) sustaining a concussion, or (b) having worse outcome or slower recovery from this injury?

d. Are multiple past concussions associated with current cognitive difficulties or symptoms (e.g., headaches) in adolescent student athletes?


2. Improving the Methodology for Assessing Cognitive Impairment Following Concussion.

Concussions can have an immediate and large adverse effect on cognitive functioning. This can interfere with an adolescent’s ability to function in daily life and school. We will conduct a series of studies, using a database of over 45,000 student athletes, that will examine the reliability, accuracy, and clinical usefulness of computerized cognitive testing as a component of a sport concussion management program. We will collaborate with our colleagues from Vancouver (Canada), Calgary, Philadelphia, Helsinki, Tampere (Finland), Waterville (ME), and Newcastle (Australia) on this research program.

3. Developing a Cognition Endpoint for TBI Clinical Trials.

Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We are engaged in a multi-year programmatic research effort to develop and validate a cognition endpoint for TBI research and clinical trials (see PubMed).

4. Improving Exertional Testing and Return to Play Protocols.

Injured athletes are expected to undergo a progressive series of exercises and exertional tests, spanning several days, prior to be cleared to return to contact sports. It is important to understand and document the effects of exertional testing on athletes who are not injured so we have normative reference values to compare to athletes who are injured. We will examine the effects of exertional testing on cardiac physiology, balance, cognition, and subjective symptoms in both uninjured and injured athletes. We will pursue this research with our collaborators from Canada.

5. Active Rehabilitation for Children and Adolescents Who are Slow to Recover from Concussion.

There are no evidence-based guidelines for providing treatment and rehabilitation services to student athletes who are slow to recover from concussion. An active rehabilitation treatment program for children and adolescents who are slow to recover following concussion has been offered at the Montreal Children’s Hospital Trauma Center since 2007. This group of clinicians and researchers is part of our research network. In addition, we are collaborating clinicians from GF Strong Rehabilitation Hospital in Vancouver, Canada to do a small clinical trial on active rehabilitation with adolescents who are slow to recover. Through a series of studies with our Canadian collaborators, we will advance knowledge and refine treatment strategies for children and adolescents who have persistent symptoms and problems following their injuries.

6. Are Former Athletes at Risk for Future Brain Disease and Neurodegeneration?

There have been thousands of media reports relating to former athletes being at increased risk for future brain disease and neurodegeneration. The most commonly used term for this disease is “chronic traumatic encephalopathy,” but it has also been claimed that other diseases, such as Alzheimer’s disease and amyotrophic lateral sclerosis (“Lou Gehrig’s disease”), could be linked to repetitive concussions. The scientific evidence, however, linking athletics and repetitive injury to brain disease is limited. We will pursue national and international research on this topic. For example, we will collaborate with our colleagues in Australia to complete a study on the neurobiological and cognitive health of former professional rugby players. For this study, the retired players will complete comprehensive cognitive assessment and undergo advanced brain imaging (including diffusion tensor imaging to examine the microstructural integrity of white matter and magnetic resonance spectroscopy to examine neurometabolic functioning).

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