rNews Medical Life Sciences
March 20, 2023
The degenerative brain disease known as CTE, or chronic traumatic encephalopathy, has become a specter haunting football. One-time stars-;like the late NFL defensive backs Irv Cross and Dave Duerson and the Hall of Fame center Mike Webster-;who were all once heralded for their swaggering on-field heroics, later found themselves condemned to far less glamorous retirements, stuck with years of progressively declining brain health, plagued by forgetfulness, disordered thinking, and poorly regulated emotions.
Now, a new study led by the Boston University CTE Center suggests the shots players take on the path to fame and glory may have a wider impact on their brains than previously known. Researchers found repetitive blows to the head may also lead to less white matter in the brain, potentially causing impulsive behavior and other thinking-related problems, whether or not someone has CTE. The research, published in Brain Communications, showed those who start playing tackle football at an early age or play it for more than 11 years are at greater risk.
“Just because you aren’t diagnosed with CTE doesn’t mean there isn’t something structurally damaged in the brain,” says neuropathologist Thor D. Stein, a BU Chobanian & Avedisian School of Medicine associate professor of pathology and laboratory medicine. “Damage to the white matter may help explain why football players appear more likely to develop cognitive and behavioral problems later in life, even in the absence of CTE.”
Damage from Football’s Repeated Hits
White matter is the brain’s cabling, made up of axons, or nerve fibers, that connect its billions of cells. It accounts for about half of the human brain’s volume-;without it, our cells (the gray matter) wouldn’t be able to communicate with each other.
“A lot of neuroscience and degenerative disease study is focused on the neurons or cells themselves, but increasingly people are recognizing that there can be damage to the connections,” says Stein, leader of the BU Alzheimer’s Disease Research Center’s neuropathology core and a staff neurologist at two Boston-area Department of Veterans Affairs’ healthcare systems. “The cell itself might look okay, but its connection is not intact-;and that was what we wanted to look at in this study.”
To dig into the effect of repeated hits to the head on these connections, the researchers analyzed the brains of 205 amateur and professional football players. All had asked that their brains be donated to the BU-hosted UNITE Brain Bank, which holds more than 1,200 brains, after their deaths. A majority of the former players-;75.9 percent-;had reportedly been functionally impaired and, the researchers found, many (but not all) also had CTE.
For the study, Stein and his colleagues split themselves into two groups, blinded-;or working independently-;from each other. One group conducted a pathological examination of the brains, peering at samples through microscopes and dissecting white matter tissue to test protein levels. The second group evaluated medical records and interviewed family members about symptoms.
Stein was part of the pathological team. He concentrated his efforts on investigating myelin, a membrane of lipids and proteins that wraps around and strengthens the brain’s cabling-;like the plastic casing around insulated wire. Using biochemical tests called immunoassays, he measured the levels of two myelin proteins, myelin-associated glycoprotein (MAG) and proteolipid protein 1 (PLP). “How much of these proteins are present is a proxy of the integrity of the white matter,” says Stein. Less myelin, less efficient connections between brain cells.
The researchers targeted the frontal lobe, the part of the brain that controls many executive functions, from memory and attention to planning and self-control. It’s also on the front lines when it comes to football hits and concussion impacts. They found that the more years someone played football, the less PLP they had; those who played for more than 11 years had less PLP and MAG than those with shorter careers. They also discovered that donors who started playing tackle football earlier had lower PLP levels. Stein suspects that young, developing brains are especially susceptible to damage from football’s repeated hits.
“Maybe young folks playing at an early age, their connections might be particularly susceptible to damage,” he says. “We found if you started at a younger age, you were more likely to have less of these white matter–associated proteins decades later in life.”
During their lifetimes, the former players probably struggled to plan their days, control their emotions, and understand the consequences of their actions, says Stein. “In our study, we found that, in those over 50 years of age, lower measures of white matter were associated with an impaired ability to perform normal activities of daily living, such as paying bills, shopping, and cooking, as well as with more impulsive behavior.”
Assess the Risk of Contact Sports
The latest study should allow researchers to give families some closure-;by explaining what caused their loved ones’ sliding brain health. The research could also provide a foundation for helping future patients.
“These results suggest that existing tests that measure white matter injury during life, including imaging and blood tests, may help to clarify potential causes of changes in behavior and cognition in former contact sport athletes,” says Michael L. Alosco, a lead author on the study and a Chobanian & Avedisian School of Medicine associate professor of neurology. “We can also use these tests to better understand how repeated hits to the head from football and other sports lead to long-term injury to the white matter.”
Stein hopes their work will also help people better assess the risks of playing football, along with other contact sports.
“There’s a cumulative risk-;the more you play, the more your risk is increased,” says Stein, who backs the Concussion Legacy Foundation’s Flag Football Under 14 campaign. “One message we try to get across is you don’t need to be playing tackle football at a very young age-;if you can just shrink those cumulative years of play down a little bit, you can make a really big impact on brain health. This study is more evidence of that.”