NFL LONG Study Research

Why are we conducting this research?

The mission of this five-year study is to improve the long-term neurological health of former NFL players, while enhancing the health and safety of current and future athletes at all competitive levels. In partnership with our NFL player participants, we stand committed to conducting research of the highest standard that directly improves the lives of current, former, and future NFL players.

Research updates

Thus far, our work1,2 suggests that:

  • Former NFL players can improve their health related quality of life by:
  • The beneficial effect of improving these factors is larger than the potential negative effect of concussions on depression, anxiety, and behavioral dyscontrol.
  • The beneficial effect of improving these factors is comparable to, but slightly smaller than, the potential negative effects of concussions on cognitive symptoms.
  • While history of sport-related concussions is associated with some long term outcomes, years of playing football is not.

In summary, there are steps that former NFL players can take to improve their health related quality of life. The effect of these steps may help mitigate the potential negative effects of concussions they have sustained.

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 wellbeing.
  • 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, Michael McCrea, PhD, ABPP-CN, and Ruben Echemendia, MD.

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 CTE. At the end of this study, we plan to translate the results of these tests into interventions to be tested in clinical trials.

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 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 Alzehimer’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.

1. Walton SR, Kerr ZY, Brett BL, et al.  Health-promoting behaviours and concussion history are associated with cognitive function, mood-related symptoms and emotional-behavioural dyscontrol in former NFL players: an NFL-LONG Study.  British Journal of Sports Medicine.

2. Brett BL, Walton SR, Kerr Z, et al.  Distinct Latent Profiles based on neurobehavioural, physical and psychosocial functioning of former National Football League (NFL) players: an NFL-LONG study.  Journal of Neurology, Neurosurgery, Psychiatry.

The commitment and compassion with which we care for all children and families is matched only by the pioneering spirit of discovery and innovation that drives us to think differently, to find answers, and to build a better tomorrow for children everywhere.

Kevin B. Churchwell, President and CEO

Connect with Boston Children's Hospital