New techniques may detect CTE in brains of living former NFL players

Tempe campus

April 10, 2019

When you search online for “CTE and NFL,” you’ll find a list of 54 professional football players who have died and were diagnosed with the degenerative brain disease chronic traumatic encephalopathy, or CTE — names like Frank Gifford, Ken Stabler, Bubba Smith and Andre Waters. It’s a smart guess that hundreds more are unaccounted for.

Next, you’ll see a list of living ex-NFL players including Brett Favre, Bernie Kosar and Jim McMahon, who have been diagnosed with “likely CTE.” And therein lies the problem: CTE cannot be detected until autopsy, leaving questions about who has it, when they get it, and how it affects their lives. To confirm CTE, scientists must rely on players and families who agree to donate their brains to research.

But now, Arizona researchers are playing a key role in the search for new ways to identify CTE before death. In a study released online in the New England Journal of Medicine, a cross-national team, including local researchers from Arizona State University, Banner Alzheimer’s Institute, Mayo Clinic Alix School of Medicine and Boston University have brought us a step closer to diagnosing CTE in living former NFL players.

The study demonstrates that an experimental positron emission tomography (PET) scan can detect a hallmark of CTE, the accumulation of abnormal tau protein in brain regions of living former NFL players who have cognitive, mood and behavior symptoms. The researchers also found that the more years of tackle football played (across all levels of play), the higher the tau protein levels detected by the PET scan.

Corresponding author Robert Stern, a professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine (BUSM), said that “the results of this study provide initial support for the flortaucipir PET scan to detect abnormal tau from CTE during life. However, we’re not there yet,” he cautioned. “These results do not mean that we can now diagnose CTE during life or that this experimental test is ready for use in the clinic.”

CTE is a neurodegenerative disease associated with repeated blows to the head. Symptoms of CTE can begin in a patient’s late 20s or early 30s. Common behaviors are anger, lack of impulse control, depression, suicidal thinking and paranoia. This is a brain disease for which there is no treatment.

In CTE, a protein called tau forms clumps that slowly spread through the brain, killing brain cells, and patients typically show a relative lack of the amyloid plaques which are associated with Alzheimer’s disease.

Diego Mastroeni, a researcher with the ASU-Banner Neurological Disease Research Center at the Biodesign Institute, first got an “up-close-and-personal” look when a member of Mastroeni’s family shared his concerns about memory issues and how his NFL career may have affected his brain. Mastroeni was recruited to speak at a meeting of Arizona’s NFL Alumni Association.

Diego Mastroeni

“This was 2015. The NFL concussion settlement was in full form, but players needed to be diagnosed with dementia or mild cognitive impairment in order to qualify,” said Mastroeni. “By this time I was having personal communication with well over 50 retired NFL players. They were calling and emailing me daily, pleading for help, asking what to do.”

Methods for diagnosing CTE in living patients were undependable and expensive. A single brain scan cost about $10,000 at the time.

“When I say this is a vulnerable population, I mean it,” said Mastroeni. “It got to the point that I needed to find a way to help these guys at no cost to them.”

From his work with Alzheimer’s, Mastroeni knew that chances were good that CTE was brewing in the brain before symptoms began appearing.

“Unfortunately, efforts to develop a diagnostic tool during life have largely been unsuccessful,” said Mastroeni. But Mastroeni also knew that advances in brain imaging techniques like PET scans were revolutionizing the field, providing a means to reliably detect and track brain changes in living subjects before the onset of memory loss in neurological conditions like Alzheimer’s disease.

Mastroeni reached out to Marwan Sabbagh, a neuroscientist, formerly with Banner Alzheimer’s Institute and now with the Cleveland Clinic, and asked if he’d be willing to meet with Mastroeni’s relative and others who had expressed interest.

Next, Mastroeni connected with Eric Reiman, a leader in neuro-imaging, University Professor of Neurology at Arizona State University and executive director of Banner Alzheimer’s Institute, who knew just the right people with whom to partner.

“A couple weeks later, Bob Stern flew out from Boston and we hashed out a plan to image all the guys we could; some at BUSM, some at Banner and some at Mayo, at no cost to them,” said Mastroeni. Stern leads a CTE Center at BUSM where he is working to develop accurate methods to detect and diagnose CTE while the player is still alive, gaining a better understanding of risk factors for the disease — and understanding why some players get it and some do not.

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In 2014, Mastroeni sent a letter to NFL players who lived in Arizona, offering them the opportunity to be part of a study. After several appearances at the local NFL alumni chapter, some 60 players were eager to participate. Some of the patients were included in the study, and others did not meet the inclusion criteria. The state of Arizona provided enough funding to launch the study in Arizona, while researchers in Boston also recruited participants and secured their own funding.

The Arizona force was strong, involving not only Mastroeni and Reiman’s team in Arizona, but also neurologists David Dodick and Charles Adler at Mayo Clinic Alix School of Medicine in Phoenix. The multidisciplinary group of researchers also included Brigham and Women’s Hospital and Avid Radiopharmaceuticals.

In the study, experimental flortaucipir PET scans (flortaucipir is the chemical used to measure tau in the PET scans) were used to assess tau deposition, and FDA-approved florbetapir PET scans were used to assess amyloid plaque deposition in the brains of 26 living former NFL players with cognitive, mood and behavioral symptoms (ages 40-69). There was also a control group of 31 same-aged men without symptoms or history of traumatic brain injury.

Results showed that the tau PET levels were significantly higher in the former NFL group than in the controls, and tau was seen in the specific areas of the brain that have been shown to be affected in post-mortem cases of neuropathologically diagnosed CTE.

Interestingly, the former player and control groups did not differ in their amyloid PET measurements. Indeed, only one former player had amyloid PET measurements comparable to those seen in Alzheimer’s disease (AD).

“Our findings suggest that mild cognitive, emotional and behavioral symptoms observed in athletes with a history of repetitive impacts are not attributable to AD, and they provide a foundation for additional research studies to advance the scientific understanding, diagnosis, treatment and prevention of CTE in living persons,” said co-author Reiman. “More research is needed to draw firm conclusions, and contact sports athletes, their families and other stakeholders are waiting."

With support from NIH, the authors are working with additional researchers to conduct a longitudinal study called the DIAGNOSE CTE Research Project in former NFL players, former college football players and persons without a history of contact sports play to help address these and other important questions. Initial results of that study are expected in early 2020.

Funding for this study was provided by grants from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company), the National Institutes of Health (grant numbers R01NS078337, U19AG024904, 1UL1TR001430); the state of Arizona; and the U.S. Department of Defense (grant numbers W81XWH-13-2-0063, W81XWH-13-2-0064, W81XWH-14-1-0462). All flortaucipir and florbetapir PET radiotracers were provided by Avid Radiopharmaceuticals.

Top image: CTE is a neurodegenerative disease associated with repeated blows to the head for which there is no treatment. Common behaviors include anger, lack of impulse control, depression, suicidal thinking and paranoia.

ASU workshop showcases the challenges for those newly released from prison

Shawn served three years in prison for burglary, then walked out to face a dizzying array of requirements he had to fulfill with almost no help and no money. He had to pay for drug testing and probation but wouldn’t get his disability check for another week, and his landlord was demanding a $50 deposit right away.“Shawn” was one of the characters in a role-playing scenario held Tuesday by th...

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Arizona Impact

ASU workshop showcases the challenges for those newly released from prison

Downtown Phoenix campus

April 10, 2019

Simulation participants navigate probation, rent, transportation as they reenter society

“Shawn” was one of the characters in a role-playing scenario held Tuesday by the Center for Child Well Being at Arizona State University. About 100 people participated in the “reentry simulation,” each assuming the identity of someone who was recently released from prison. The participants included students, staff, faculty and community members, each of whom received a packet describing their character’s prison record, living and employment situations and everything he or she needed to accomplish every week to avoid being sent back to jail: look for a job, undergo drug testing, pay restitution, pay rent, pay child support, buy food, attend Alcoholics Anonymous.

The simulation was put on by the U.S. attorney’s office and was based on input from real people who have been released from prison. The goal is to demonstrate what it’s like for men and women to make their way through the system.

“We release people back into their communities every day, and with very little instruction,” said Tasha Aikens, a reentry specialist for the U.S. attorney’s office in Arizona, who runs the simulation for any group that requests it.

The simulation was divided into 15-minute segments, each representing one week. The room had 15 stations, representing the obligations of a returning citizen — probation, social services, bank, landlord, etc. Every participant had several tasks to complete each week.

All the participants in the reentry simulation were required to buy bus passes and food, find jobs, get tested for drug use and pay rent. They went from table to table in the room, waiting in long lines, to accomplish each task.

Photo by Charlie Leight/ASU Now

Princess Lucas-Wilson, an instructor in the School of Social Work, volunteered at one of the stations at Tuesday's reentry simulation.

Photo by Charlie Leight/ASU Now

Lawrence Thomas, a social worker who participated in Tuesday's reentry simulation, receives a "check" for $25 after "donating" plasma.

Photo by Charlie Leight/ASU Now

The responsibilities were confusing and overwhelming. Every obligation required a bus pass. Even bus passes could not be purchased without handing over a bus pass.

The first week, Shawn, one of the lucky ones who left prison with $20, was able to purchase the all-important state ID card for $15, then sell his plasma for $25 to pay his $30 probation fee. He went to the “court,” handed over a bus pass and was told he needed to cash his plasma check before paying the fee. So he used another bus pass to go to the bank and cash the check and then another bus pass to finally pay the fee.

The second week was more stressful. Shawn had to wait in the church line to borrow a bus pass, which he used to buy more bus passes, then go back to the church to repay the bus pass before going to collect his disability check.

The simulation included real-life scenarios. Everyone who took a drug test had to pull a card from a deck to tell them whether it was “clean” or not. Every week, the participants received a card with an unplanned situation — like Shawn’s landlord discovering that he had a dog and needed to pay a $50 deposit.

In the third week, Shawn was waiting in line to pay his rent when the sheriff came by, saw that Shawn had not completed his second-week drug testing and sent him back to jail.

In the guided discussion after the simulation, many of the participants described how out of control they felt.

“A lot of it is pretty demeaning,” said Anthony Evans, a senior researcher for the L. William Seidman Research Institute in the W. P. Carey School of Business. The institute is working with Televerde, a call center operator that has been a leader in employing prisoners and people who have left prison. Evans said he decided to experience the simulation to gain insight into what Televerde’s workforce is facing.

“People in positions of authority should be encouraged to attend one of these,” he said.

The process was eye-opening even for practitioners. Molly Hahn-Floyd, a doctoral student at Northern Arizona University who works in adolescent behavioral health, said that during the simulation, she didn’t go to the church or social services or any other place that offered help.

“And I don’t know how many times I’ve preached to people, ‘Ask for help,’” she said.

Jan Wethers, reentry coordinator for the Arizona Department of Corrections, portrayed the mean pawn shop owner, who gave Shawn $10 for a $50 CD player.

“Take the bus sometime,” she told the practitioners. “See what it’s like when it’s hot and you have kids in tow and grocery bags.”

Empathy is critical, but so is responsibility, she said.

“You must hold them accountable. That is very, very important,” she said.

Many participants described how returning to jail felt inevitable — and almost a relief.

“If you’re released to a community and your family wants nothing to do with you and you have no job and no home and you have all these obligations, it makes sense to go back,” Aikens said. “They know your name in jail. You have food in jail. I get it.”

For a person who’s newly released, thinking about returning to prison can be a “comfort zone,” according to Theron Denman Jr., who left prison a year ago. He volunteered at the simulation “treatment” table and addressed the participants during the discussion.

“I was scared to drive, I was scared of the police, I was scared of technology,” he said. “If I hadn’t had the support of my family over this past year, I would’ve wanted to go back.

“But that’s not my comfort zone anymore. Volunteering here today is a beautiful thing.”

In the fourth week, Shawn got out of jail, bought bus passes, got food, completed weekly treatment, paid for a drug test and checked in with his vocational rehabilitation case worker. All the boxes were checked.

But it didn’t matter. While he was in jail during Week 3, he missed paying rent. Shawn was homeless.

The reentry simulation was a kickoff to the National Children of Incarcerated Parents Conference to be held next week by the Center for Child Well Being, part of the School of Social Work. The conference will include some events that are open to the public. On Sunday, the opening reception will feature photographer Isadora Kosofsky, who documents prison visitations between parents and children. Additionally, Denali Tiller, director of “Tre |Maison |Dasan” will screen her film and discuss the three young boys featured. On Tuesday, Rudy Valdez, director of HBO's “The Sentence,” will screen his documentary and discuss the effects of incarceration on his nieces. A panel discussion will follow, featuring people who have been affected by incarceration.

Top image: Tasha Aikens, a reentry specialist with the U.S. attorney's office, led a "reentry simulation" Tuesday at the Westward Ho in downtown Phoenix. About 100 students, staff, faculty and community members participated in the workshop, in which they took on the persona of someone who recently left prison and had to navigate all the tasks necessary to avoid being sent back to jail, such as getting a job, being drug tested and paying rent. Photo by Charlie Leight/ASU Now