Imaging study looks at brain injury in former NFL players

Dr. Jennifer Coughlin is an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins School of Medicine.
Dr. Jennifer Coughlin is an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins School of Medicine. (Lloyd Fox, Baltimore Sun)

A recent study of retired NFL players by Johns Hopkins medical researchers adds to growing evidence linking football with brain damage.

The study published last month in the journal Neurobiology of Disease focused on nine retired NFL players, but the results add to a growing body of research and anecdotal accounts associating brain disease with the blows to the head that are a common part of football and other sports.


Using an improved brain-imaging technique, Hopkins researchers found evidence of brain injury and repair in the former NFL players while it did not appear in a control group of nine healthy men had who never played professional football.

Because of the small number of subjects and lack of consistent results, however, the retired players' cognitive performance tests did not present clear evidence of mental impairment, said the researcher who conducted that part of the study. The sample was also too small to correlate the results of another element of the study, eight cognition tests — including measures of word memory, verbal fluency and attention — with the images showing damage chiefly in three parts of the brain, the report said.


Dr. Jennifer M. Coughlin, the lead project researcher, said the study is a step toward bridging knowledge gaps on the association between playing violent sports such as football with mental decline and mood disorders later in the player's life. She was one of 19 co-authors of the study, 17 of whom are with the Johns Hopkins Medical Institutions.

"Ultimately, I'm really hoping that someday we're able to answer the questions from the players and their family members of whether football really caused brain injury," said Coughlin, an assistant professor of psychiatry and behavioral science at the Johns Hopkins University School of Medicine. "We don't have these answers for family members yet."

The new imaging technology — developed in about the past seven years — promises a way to study how brain injury develops over time in living people, Coughlin said.

The study included 11 former players, nine of whom took part in both the imaging and the cognitive test portion of the study. The former players, 57 to 74 years old, played a variety of positions, though there was no former quarterback in the group. When the research was done, the men had been out of the NFL for 24 to 42 years.

The nine reported a range of experiences with concussion as defined by the American Academy of Neurology. Concussion does not necessarily mean that the victim loses consciousness, but early symptoms can include headache, dizziness, lack of awareness of surroundings, and nausea or vomiting. Later symptoms can include persistent headache, poor attention and memory loss.

Of the nine players who took part in both parts of the study, one reported 11 concussions, one said he'd had none. Most reported two to five.

The Hopkins imaging study was conducted at the molecular level, using a radioactive compound to track a protein in the brain that concentrates in areas that are injured or are recovering from damage. The new compound provides a more reliable picture than earlier chemicals used for the purpose when viewed with positron emission tomography, or PET scan.

Using these injections, researchers found elevated levels of the so-called translocator protein showing up in certain brain regions. The images of the radioactive hot spots in colors introduced by the imaging system — red showing twice as much protein concentration as blue — were overlaid on black-and-white magnetic resonance imaging — MRI — pictures showing brain structures.

Three brain regions showed elevated levels of the telltale protein: the right and left supramarginal gyrus, and the right amygdala. MRI images from players also revealed evidence of significant shrinkage of the right hippocampus, which might be a result of prior damage to that area. Those parts of the brain are engaged in functions that include language perception and processing, empathy, spatial orientation, memory, decision-making, and emotional reactions.

Results of eight cognitive tests on the players did not show diminished function, said Cynthia A. Munro, a Johns Hopkins neuropsychologist who conducted the examinations involving word memory, pronunciation, visual attention and problem-solving.

"No one was impaired on any measure of that," said Munro, an associate professor of psychiatry and behavioral sciences. She said there were low scores on some memory test portions, "but no consistent memory deficits were found."

Christopher Nowinski, who co-founded the Sports Legacy Institute in 2007 to advocate study, treatment and prevention of brain injury in athletes and others at risk, said that while many questions remain, he's confident there is a link between NFL play and brain damage.


Nowinski noted a recently updated study of the brains of deceased former NFL players conducted by the Boston University CTE Center, which focuses on chronic traumatic encephalopathy, a degenerative disease first identified in the 1920s and called dementia pugilistica, commonly referred to as punch drunk syndrome, for its association with boxers. There's no test for the disease in living people; it can only be confirmed in postmortem brain studies.

The study released in the fall found that 76 of 79 former NFL players' brains showed evidence of CTE. The study showed evidence of CTE in 101 of 128 brains — nearly 79 percent — of football players at all levels: professional, semipro, college and high school.

Nowinski said the link between football and CTE — associated with symptoms that include memory loss, impaired judgment, confusion, impulse control problems, depression and aggression — is clear enough.

"There's no other explanation which is reasonable," he said. Asked about the Hopkins study, he said, "It wouldn't surprise me that they're finding other markers of this disease."

Coughlin and Munro have begun work on another study that will involve more players, including some who are still active. The ideal project, they said, would follow players from their youth through their playing days and beyond, allowing researchers to track changes over time and take better account of the role that aging or other disorders might play in brain damage or cognitive decline.

Coughlin, who specializes in using imaging technology to track this particular protein as a marker of brain damage, is encouraged by the emergence of the new radioactive compound and its prospects for further research.

"We're excited to share that this new tool can be used by all researchers interested in studying this important public health question," she said.

NFL Commissioner Roger Goodell has said the league is taking steps to prevent head injuries, including fining players for head-on collisions, establishing procedures for returning players to the field after concussions and having neurosurgeons on the sidelines during games.

He told a meeting of neurosurgeons last year that the league is committed to spending $100 million over the next 10 years for research on brain injuries. A combined effort with General Electric, called the GE NFL Head Health Challenge, supported the Hopkins research, which also was partly funded by the NFL Foundation, an organization headed by NFL executives.


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