NFL-LONG Study: Improving life beyond the game

NFL-LONG stands for Neurologic Function across the Lifespan: a Prospective, LONGitudinal, and Translational Study for Former National Football League Players. The NFL-LONG Study is a state-of-the-art research program to develop strategies for preventing and treating the neurological health problems experienced by former NFL players.

By joining our program, former NFL players will have the opportunity to:

• Enter clinical trials of the most promising therapies that emerge from our work
• Undergo cutting-edge diagnostic studies of neurological health
• Receive regular updates regarding our progress and research findings
• Contribute to the development of preventative measures and therapies for maximizing the long-term brain health of former NFL players

Overall goals of the NFL-LONG Study

We are investigating ways to diagnose neurological problems in living retired NFL players. We are also looking at several experimental treatments that have the potential to improve health and quality of life for former players and young athletes at risk of developing neurological problems in the future.

In addition, we are assessing the association between concussions, sub-concussive blows, and clinical outcomes. We hope to provide former players, current athletes, coaches, and parents more clarity on the potential relationship between concussive brain injury and long-term health outcomes.

Through this research, we aim to help former NFL players who are experiencing neurological issues. At the same time, we will be working to develop knowledge that can be used in the future to improve the health and well-being of young athletes who play football and other high-impact sports.

Arm 1: Clinical study

Our clinical research teams are assessing the neurological health status of former NFL players and using the data to determine risk factors associated with long-term health problems. The purpose of this study is to measure the prevalence of neurological health issues among retired NFL players. This study will also help us identify at-risk players who may choose to participate in future interventional studies.

Stages of the study include:

• Health survey: In the first stage of this study, we will survey all participants to gather self-reported health data.
• Neurological health screening: After the survey is complete, we will conduct telephone assessments of participants’ cognitive and psychological health.
• Annual health survey: Each year for the duration of the five-year study, we will conduct follow-up surveys of each participant’s health and well-being.
• In-person research evaluation: We will conduct in-person evaluations of a subset of players. Assessments will include detailed clinical assessments, advanced MRI, PET imaging of tau, amyloid, and inflammation, proteomic biomarkers, and genotyping.
• Follow-up in-person research evaluations: Former players who exhibit progressive impairment will undergo a second in-person research evaluation three years after their initial assessment.

This evaluation and design will create the most richly characterized cohort of former NFL players to date and will allow us to assess health outcomes over a 20-year span. The clinical study is being led by Kevin Guskiewicz, PhD, ATC; Michael McCrea, PhD, ABPP-CN; and Ruben Echemendia, PhD.

Arm 2: Basic science

The basic science teams are assessing four specific treatments for health problems related to repeated concussions. The purpose of this laboratory part of the study is to research the physiology, prevention, and possible treatments for neurological problems seen in former NFL players.

Four treatments have shown promise in reducing the impact of neurological damage in previous laboratory tests:

1. An antibody to cis-tau, the toxic form of tau that leads to hyperphosphorylation. Tau is a protein that regulates nerve cells. In brains affected by neurological problems, including CTE, tau proteins build up and form tangles within the brain, a process called hyperphosphorylation. We will be testing this antibody to see if it can prevent the buildup of tau tangles in the brain.
2. The NMDA receptor antagonist, memantine. This drug has shown promise improving memory in patients with Alzheimer’s disease.
3. Low-dose carbon monoxide, which has shown promise in the treatment of other forms of brain injury.
4. Environmental enrichment with regular physical and cognitive exercise, which has shown promise in laboratory settings.

At the end of the study, we plan to translate the therapies that appear most promising into clinical trials for former NFL players who experience long-term health problems related to concussions and sub-concussive blows.

Basic science research teams include Leo Otterbein, PhD, and Rebekah Mannix, MD, MPH.