NFL players participate in study that could predict CTE decline

BALTIMORE. Jonathan Martin thinks he does the right thing most of the time.

A former hitter with the Miami Dolphins and the San Francisco 49ers, he retired at 26 years old before the semi-concussive headbutts that mark his position could do more damage. He lost 50 pounds, took up yoga and meditation, and bounced from job to job, enrolling in an MBA program at the University of Pennsylvania.

But Martin, now 32, believes he potentially had dozens of concussions while playing football and had bouts of anxiety and depression, all symptoms associated with chronic traumatic encephalopathy, a degenerative brain disease that affects footballers.

Martin’s concern prompted him in 2019 to join a study at Johns Hopkins University that could help scientists develop treatments for the symptoms and diseases associated with brain injury and CTE.

“I wanted to be at the forefront of the solution,” said Martin, who was the target bullying by a teammate it made headlines in 2013. “There should be more attention to head injuries. I want to know how I can keep my mind blurry.”

The study, now in its second phase, is looking into why the brains of former football players continue to work overtime to repair themselves years after the athletes have stopped playing. Using a PET scan, the researchers track brain cells known as microglia that remove and repair damaged neurons. These cells are usually active after trauma, including concussions, and become less active as the brain heals.

“Microglia and the molecule they work with are basically the sanitation workers of the brain,” said Jonathan Lifshitz, director of the Translational Neurotrauma Research Program at Phoenix Children’s Hospital, who is not involved in the study at Johns Hopkins University. “They’re like FEMA: they’re on high alert, and when they’re needed, they’ll come and take action.”

Active microglia are generally welcome as they help the brain recover, but remaining active for long after an injury ends could mean other problems.

While the activity of these microglia has been found in other people who have suffered traumatic brain injury – for example, in people involved in a car accident – these groups can be difficult to find and track over the course of an extended study. NFL players, however, are a distinct group that is easy to identify and, like Martin, they may want to get involved.

Dr. Jennifer Coughlin, an associate professor at Johns Hopkins University School of Medicine and the study’s lead investigator, first observed overtime of brain repair cells in a pilot study that began in 2015. Testing four active NFL players and 10 former pros. whose career ended within 12 years, Coughlin’s team found higher levels a biomarker that increases with microglia activity.

This chronic activity, she said, could be a sign that players are at risk of developing other problems associated with brain injury, such as memory impairment, mood disorders or Alzheimer’s disease.

“We want to know whose brain is being healed and why,” Coughlin said. “It could provide information about new treatments.”

To provide more clarity, Coughlin and the researchers focused the second phase of the study on younger former players who were less likely to have vascular disease or other features that could independently confound interpretation.

Martin, who has struggled with depression since the bullying scandal, deepened after he left the NFLI wonder if football plays a role. He approached the Concussion Legacy Foundation to learn more about any potential connections, and the group pointed him to the Johns Hopkins study.

“Based on my behavior, the question came to mind: is there something wrong with me, besides the usual depression?” Martin said. “Anyone who plays football knows that hitting yourself in the head is bad.”

He was first screened in late 2019 and, after a study delay due to the coronavirus pandemic, returned to Baltimore in March for two days of follow-up tests.

On the first day, Martin answered questions about changes in his cognitive abilities and mental health since his first visit. He returned the next morning for a PET scan, an imaging test that will monitor his brain activity by tracking a chemical injected into his arm.

During the 90-minute scan, Martin meditated to overcome his claustrophobia from having his head inside a tight-fitting metal cylinder for so long. Karen Edmonds, a nuclear medicine specialist, provided him with a wet uniform that, once hardened, kept Martin’s head still.

“Once it’s molded, it fits like a glove,” she said.

The anesthetist then inserted a catheter into Martin’s left arm for about 35 blood samples to be taken during the scan.

Once in the PET room, Martin lay on his back on the table with the blanket thrown over him and slid back until his head was inside the scanning tube. Then a screening was introduced into his right arm, and Edmonds watched his action on the monitor.

“The goal is to see how much of the radio signal lights up in the brain,” Edmonds said. “In the beginning, there is only one dose, and then we watch how quickly it deteriorates.”

After the test was over, Edmonds pulled the table with Martin out of the pipe. “I’m claustrophobic, but I just got over it,” Martin said. “You’re definitely bored, but that’s for sure.”

Coughlin arrived to remove the arterial catheter, which took about 15 minutes.

She has tested 22 former NFL players and 25 other athletes so far, and hopes to test just 70 participants to better isolate potential brain triggers. Genetics, other medical conditions, a player’s position on the pitch and the time he started playing football may all play a role, Coughlin said.

“This will allow us to analyze what factors exist for people with permanent brain damage,” she said.

Even with the involvement of Martin and other players, the Johns Hopkins study is still relatively small and is just beginning to understand how an injured brain behaves. But it has the potential to help identify the early onset of diseases and symptoms associated with head trauma, not only in football players, but also in people who have previously been involved in bicycle accidents, car accidents and other collisions.

“Currently, there’s no really good way to diagnose Alzheimer’s or Parkinson’s early,” said Jay Alberts, a neuroscientist at the Cleveland Clinic’s Center for Neurological Rehabilitation. “It’s very important to be able to raise a yellow or red flag.”

The study is blind, which means that Martin and the other participants are not told the results of their individual tests. But Martin said that participation is about helping others as well as helping yourself.

“It’s all part of the research I’m passionate about to make the game better,” he said.