Autopsies of four young veterans found the earliest signs of chronic traumatic encephalopathy, or CTE, in their brain tissue, Boston researchers reported Wednesday.
They compared the brain tissue of some of the youngest athletes ever found with signs of early CTE, in their teens and 20s, and concluded the abnormalities were nearly identical.
"It's very distinctive," said Dr. Lee Goldstein of Boston University, who led the study with Dr. Ann McKee of the VA New England Healthcare System. "You don't see this in normal individuals."
The research suggests that the cause of the injury, whether a blast or repeated blows, doesn't matter — it can trigger the same disease-causing process, said McKee, who has long studied the athlete connection.
Further experiments with mice showed that a single blast, equivalent to a roadside bomb, was enough to start the damage — offering a model to help scientists better understand these wounds and perhaps how to treat them, the team reported in the journal Science Translational Medicine.
CTE is a progressive disease linked to multiple concussions. It has made headlines in recent years with the deaths of some former professional athletes, and lawsuits filed against the National Football League by others worried about the still unclear toll of a sport that can bring repeated blows to the head. Symptoms include memory problems, behaviour changes including aggression, and eventually dementia. For now, only an autopsy confirms a diagnosis.
Traumatic brain injury, or TBI, is a signature injury of the wars in Iraq and Afghanistan, most of them closed-head injuries caused by being near an explosion. While many recover fine, others have some lasting cognitive or psychiatric symptoms — and traditional medical exams can't see the damage, making it incredibly difficult to diagnose what's wrong. Additionally, scientists have long warned that many of those veterans may be at risk of long-term problems such as Alzheimer's-like dementia.
Wednesday's study, while very small, sheds important light on how damaging those TBIs can be even if the person walks away from the blast.
The four young veterans, ages 22 to 45, lived for a year or longer after their military TBIs, but complained of problems with memory, irritability, sleep and other issues before dying of suicide or other causes. Goldstein and McKee found their brains contained broken axons, the nerve fibers that act as the brain's telephone system.
More surprising: Abnormal tangles of a brain protein named tau are a hallmark of early CTE, and researchers found that tau buildup in the brains of the veterans' and the young athletes, three of them who played high school or college football and the fourth a professional wrestler. They didn't see it in the brains of four other young men who hadn't experienced concussions before death.
Three of the veterans had been exposed to blasts, while one had a different kind of concussion while deployed — and all had had at least one pre-military concussion, from football, wrecks or fights.
While that begs the question of whether the blast was to blame, Goldstein said the mouse study shows a single explosion could trigger that kind of damage. Wind from a simulated blast whipped the animals' heads like a bobble-head doll, severely shaking the brain, he explained. They experienced broken axons and blood vessels, inflammation and problems with learning and memory — and two weeks later, were forming abnormal tau.
When the animals' heads were immobilized, they escaped that damage, Goldstein said.
He said helmets may be crucial in protecting the skulls of soldiers and athletes, but they cannot protect the brain from that kind of rattling injury and might even worsen it by increasing the load on the neck.
Specialists not connected to Wednesday's study caution that far more research is needed on the possible link between this brain degeneration and TBIs, especially in veterans.
Still, "they are very important findings," said TBI researcher Dr. Amy Wagner of the University of Pittsburgh School of Medicine.
For abnormalities to begin so soon after injury triggers questions about how resilient different people are, she said: Who's more likely to recover? How many blows are too many? What other factors could make this slow-moving disease eventually worsen?
A key next step will be for brain banks, which store donated brain tissue for research, to look more closely for CTE so scientists can learn how often it occurs and in whom, said neuroscientist Dr. Sam Gandy of New York's Mount Sinai School of Medicine. He predicts that people who carry genes linked to Alzheimer's disease would be more prone to lasting damage from TBI. In an editorial in the same journal on Wednesday, he suggested studying if gene testing of would-be high school athletes or military recruits might one day help persuade the most vulnerable to avoid those occupations.
McKee said her lab so far has found evidence of CTE in more than 65 athletes and veterans, ranging from the early abnormalities to profound degeneration. She now is researching how to diagnose CTE before death, perhaps with brain scans or by measuring tau in spinal fluid.
"This work raises a number of questions for researchers to explore in further studies. In particular, the animal model developed by the researchers will enable a better understanding of the brain pathology involved in blast injuries and ideally lead to new therapies to help service members and veterans with TBIs," Dr. Joel Kupersmith, research chief at the Department of Veterans Affairs, said in a statement.Suggest a correction