Can you predict future brain damage? Hundreds of pro fighters are helping researchers find out

LAS VEGAS — It’s a study that probably couldn’t be conducted anywhere other than this hot spot for professional combatants, where marquee fights are about as common as Celine Dion concerts.

Researchers have enrolled close to 700 mixed martial arts fighters and boxers, both active and retired, in the past six years. The ambitious goal: to learn to identify early signs of trauma-induced brain damage from subtle changes in blood chemistry, brain imaging, and performance tests — changes that may show up decades before visible symptoms such as cognitive impairment, depression, and impulsive behavior.

Among the participants is 29-year-old Gina Mazany. She has a streak of pinkish-purple hair, a tattoo of a pterodactyl with a cheeseburger in its beak, and a reputation as a formidable MMA fighter worthy of her nickname, Gina Danger. Once a year, she undergoes a battery of medical tests here at the Lou Ruvo Center for Brain Health, an outpost of the Cleveland Clinic, to help suss out the toll of a career marked by concussions and blows to the head.

“I’m one of their guinea pigs,” she said.

Last month, researchers at Boston University made a splash when they identified high levels of a protein called CCL11 in the brain and spinal fluid of deceased football players with the degenerative brain disease known as chronic traumatic encephalopathy. Cleveland Clinic researchers are taking a different tack: They’re monitoring professional fighters while they’re still alive — and, most of the time, while they’re still fighting. By repeating a series of tests year after year, they hope to pick up on changes that might predict development of CTE.

Early findings are tantalizing: Over the summer, the Cleveland Clinic researchers reported that active fighters monitored over time had higher levels of two brain proteins, called neurofilament light and tau, compared to retired fighters or non-fighters. It’s still unclear whether those proteins signal a higher risk of CTE. But the discovery gives scientists a focus for future research.

Among the study’s other findings: Fighters with greater exposure to repetitive head trauma have lower brain volumes. Fighters are significantly more likely to have a cavity in their brains compared to non-fighters. And looking at seven specific features on an MRI scan can distinguish which fighters are cognitively impaired.

“I don’t know of any studies that look at both active and former athletes with the type of breadth of assessment that is going on in the fighters study,” said Robert Stern, a clinical neuroscientist who oversees clinical research at Boston University’s CTE Center and who is not involved in the fighters study.

Dr. Christopher Giza, a neurologist who directs a UCLA program for athletes with concussions and other head injuries, also praised the design of the fighters study. But he cautioned against overinterpreting changes in the brain as signs of injury or damage, when they could instead be indicators of healing or adaptive changes.

“We should keep our minds open,” said Giza, who advises several professional athletic associations on traumatic brain injury, “or we may miss out on some of the science.”

A history of ‘punch drunk’ fighters

CTE is now most associated with football players, but it was first described in boxers who were said to be “punch drunk.”

And some of the biggest names in the business are helping to fund the current research, including the UFC, the big MMA promotion company; and Haymon Boxing, which represents many top boxers. The Department of Defense, concerned about head trauma in the armed forces, is contributing, too.

Dr. Charles Bernick, a Cleveland Clinic neurologist who’s leading the study, said his funders haven’t interfered with the science. “Frankly, a study like this would never even happen” without them, he said. “The government isn’t going to pay for this.”

The fighters study is, after all, a massive undertaking — made a bit easier by the fact that it’s based in Las Vegas.

Retention has been tricky: Fewer than half the fighters who sign up for the study return for a follow-up appointment the next year, and it drops off a bit more in subsequent years. But there’s an ample pool of potential new recruits. Many professional fighters, including Mazany, live and train in Las Vegas. Others come here often for fights, or retire here when their careers in the ring are over.

Elite gyms and training centers in the area help recruit fighters to the study.

And the Lou Ruvo Center employs a social worker who helps retired fighters, many of whom are living alone with few resources, apply for disability or get help accessing medical care. As another inducement to participate, active fighters get help covering some of Nevada’s licensing requirements. The state’s athletic commission requires that fighters undergo a brain imaging scan and annual blood tests for viruses like hepatitis B, hepatitis C, and HIV. The study takes care of all that for free.

That helps bring in athletes, like Mazany, who aren’t particularly worried about their brain health and aren’t experiencing cognitive problems.

Not a typical exam room

The study’s main exam room doesn’t look like a run-of-the-mill doctor’s office.

The walls are lined up to the ceiling with signed photos of the study’s several dozen champion boxers and MMA fighters. (There’s also one of Muhammad Ali, who came to the Lou Ruvo Center for an event but never enrolled in the study before he died of sepsis last year.)

The appointment can last for up to four hours, as the researchers put fighters through exercises testing balance, cognition, and memory: Read out tiny letters from 5 feet away. Then bob your head back and forth to a metronome’s beat, and do it again. Stare at an iPad and touch the screen whenever a green circle pops up. Name as many animals as you can in one minute. Remember a long list of words, like mountain, cloud, and window.

Fighters also get three vials of blood drawn, undergo an MRI, and, once every five years, get imaging done of the blood vessels in their brain.

The fighters study is among several big ongoing studies probing the mysteries of head trauma. One, funded by the NCAA and the Defense Department, has enrolled thousands of active college athletes and cadets.

And Bernick and Stern are collaborating on a longitudinal study of former players from the NFL and varsity college football teams. (Stern also sits on a health and safety committee of the NFL Players Association and is a consultant to pharma companies. Bernick in the past has received speaking fees from the pharma companies Lundbeck, which specializes in neurological disorders, and Allergan, which markets drugs for dementia.)

While such longitudinal studies are important, it’s important to remember that the field is still young, with no consensus on the best tools to look for early signs of damage, said Michael Hutchison, a neuroscientist who directs a concussion program at the University of Toronto and consults for the National Hockey League Players’ Association.

“There’s no gold standard yet,” he said.

As for the fighters study, Bernick and his team have enough funding left to continue it for another three years. They’d like to keep it going longer, perhaps at a slightly smaller scale.

“The hope is it could be like Framingham, where you just keep following people,” Bernick said, referencing the famous, decades-long cardiovascular study of residents of a Massachusetts town.

When an exam forces tough conversations

Occasionally, Bernick spots abnormalities — in a brain scan, a blood test, or the tests that the fighter performs in the exam room — that force a tough conversation about the risks of continuing with the sport.

But most of the fighters, like Mazany, are still young and apparently healthy.

Mazany got her first concussion during her first fight, when she was 18 and living in her hometown of Anchorage, Alaska. She said she’s had a handful more in the decade since. But she said she doesn’t worry “at all” about her brain health. She likens the toll of fighting to the risks that other people take all the time, by smoking, eating unhealthily, or texting while driving.

So far, her test results have been encouraging; Mazany said her performance has actually improved over her three annual appointments.

As she trains for her next big fight — in Shanghai on the Saturday after Thanksgiving — Mazany admits she’s not sure what she’d do if her memory, balance, and reaction time take a nosedive. She’s not sure she’d reconsider her career, she said, even if researchers warned her she faced greater risk of brain damage.

She has a fighter’s drive to get out into the octagon. “We’re like that dog that runs into the glass when we see the ice cream man,” she said.