Pauline Anderson

April 25, 2017

UPDATED April 25, 2017 // BOSTON — Former National Football League (NFL) players who sustained repetitive head injuries on the field are providing researchers with new data on how this exposure is affecting their brain.

Results of one study suggest that plasma total tau could be a potential biomarker for chronic traumatic encephalopathy (CTE).

Preliminary results of another analysis found that these same retired players don't appear to be experiencing serious motor symptoms — at least not yet.

The two studies are presented at the American Academy of Neurology 2017 Annual Meeting (AAN).

The research cohort included 96 symptomatic former NFL players aged 40 to 69 years (mean age, 55.16 years) with exposure to repetitive head injury and 25 age-matched controls who had no history of playing contact sport or exposure to brain trauma, including concussion.

The players had played for a mean of 18.23 years but had been retired for about 26 years. There were significantly more African Americans in the retired players group (44.2%) than in the control group (4.05%).

The aim of the first analysis was to identify a biomarker to diagnose CTE before death, said lead researcher, Michael L. Alosco, PhD, Boston University, Massachusetts. He stressed that CTE can currently be diagnosed only at autopsy.

Study participants underwent neuropsychiatric and neuropsychological testing, and they provided blood samples. Researchers then compared concentrations of plasma total tau (t-tau).

"We are interested in identifying a specific cutoff of concentration," said Dr Alosco. "We don't know who has CTE in the sample" because the condition can't be diagnosed during life, but "we wanted to see is there a certain level of total tau concentration that put players at greatest risk."

Researchers looked at the cumulative head impact (CHI) index, a metric of estimated exposure to repetitive head injury, based on self-reported football history and estimated head impact frequencies that's extrapolated from published helmet accelerometer studies.

The analysis showed a correlation between the repetitive head impact and plasma t-tau (P = .0137) "such that more hits to the head are associated with greater concentrations of total tau in the blood," said Dr Alosco.

While the difference in mean plasma t-tau of former NFL players (2.53 pg/mL) and controls (2.46 pg/mL) was not significant (P = .6719), former NFL players had a greater range in plasma t-tau levels than controls (P = .42).

A t-tau concentration of 3.56 pg/mL was 100% specific among 12 former NFL players whereas only 5 controls went above 3.0 pg/mL.

The lack of between-group differences might be linked to factors other than CTE, said Dr Alosco. "Maybe there's chronic white matter disease associated with head trauma," for example.

He pointed out that a correlation between elevated plasma t-tau and Alzheimer's disease does not seem to appear until there's severe pathology.

"So maybe that's what we're seeing here; maybe it's not severe enough to show up in the blood."

The study provides "initial evidence for us to continue to explore plasma total tau" as a potential biomarker for neurodegenerative disease, in this case CTE, said Dr Alosco.

He reminded the audience that the study should be repeated "once we can clinically diagnose CTE during life."

A study limitation is that t-tau can be increased in a variety of conditions that damage the brain, including stroke.

"We need to look at it in combination with other blood proteins such as P-tau [phosphorylated tau]," said Dr Alosco.


Motor Function

In a separate report, another group of researchers looked at motor function in these same former football players.

"We wanted to see whether these retired NFL players who have had repetitive head injuries are showing any signs of early Parkinson's disease or parkinsonism," lead researcher, Samuel Frank, MD, associate professor of neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, and Parkinson's Disease and Movement Disorders Center, Boston, Massachusetts, told Medscape Medical News.

"We looked closely at their motor status and really, we couldn't find much."

Repeated head impacts are associated with CTE, which presents clinically as cognitive, behavior, and mood symptoms, the researchers note in their abstract. "Motor disturbances have historically been prominent in former boxers with autopsy-confirmed CTE, but this has not been the case in recent-day neuropathological studies among former NFL players with CTE," they write.

To look further at this issue, the researchers examined these 95 former NFL players aged 40 to 69 years, whom Dr Frank described as "active, working, and having family lives," and the 25 age-matched male controls, who had no history of playing contact sports or having a head injury.

To assess motor function, they used the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS), which evaluates motor function, activities of daily living (such as speech, swallowing, dressing, falling, and walking), and behavior and mood. They adjusted for age and body mass index.

MDS-UPDRS scores were low for both groups but were significantly higher in former NFL players (mean, 5.26) than in  controls (mean, 2.40) (P = .020). People with Parkinson's disease may have scores on this scale in the 10- to 60-point range, while young people without a history of head injury would score much lower.

"If you were to do the same test in my 17-year-old daughter, her score is going to be close to zero," said Dr Frank.

Most former players had normal ratings on individual MDS-UPDRS items, but a subset had slightly abnormal ratings.

On another measurement — the Balance Error Scoring System — the former players had worse scores than controls (P = .032). And for the Grooved Pegboard test, which assesses eye-hand coordination and motor speed, they also had worse dominant-hand (P = .007) and nondominant-hand (P = .001) scores.

Researchers used the CHI index which, as Dr Frank explained, goes beyond counting the number of concussions resulting in unconsciousness.

"It's not just how many times were you knocked out, but how many times were you were dazed, confused, had a zinger — so, significant injury to the head region."

They found that the CHI and MDS-UPDRS scores were not associated (P > .05).

The authors concluded that while NFL players had significantly worse motor function than controls, their test performances were still relatively normal and unrelated to repetitive head injury exposure.

Worse MDS-UPDRS scores correlated with worse psychomotor speed/executive function (P = .006).

More detailed cognitive results of the study will be published at a later date, said Dr Frank.

Linear Motion

Asked why football players might be less prone to motor dysfunction than boxers, who also sustain head injuries as a part of their sport, Dr Frank said that one theory is that football players come at each other with their head, neck, and body lined up.

"Two 300-pound linesmen exploding off the line of scrimmage are going at each other full speed, but their bodies are pretty linear in terms of that motion, whereas if you look at boxers, they get hit across the face and it's a twisting motion of the head."

It's also possible that motor problems will surface in football players later on, said Dr Frank.

"It may be that we just haven't waited long enough and that this same group will have a higher incidence of Parkinson's disease when they're in 70- to 85-year-old age range."

Asked to comment on these new motor findings, Anthony Alessi, MD, a neurologist in private practice in Norwich, Connecticut, and a fellow of the AAN, said the study "supports the clinical finding that parkinsonism is not a common finding among former NFL players." 

But he's uncomfortable with the comparison to boxers because they were not part of the study. "And I am unaware of any recent studies showing reliable data correlating PD and boxing." 

The research was supported ty the National Institutes of Health. In the first study, Andreas Jeromin, Nate Estochen, and Linan Song are employed by Quanterix. Andreas Jeromin is an advisor to Quenterix Corporation and holds stock options. For the second study, participant travel was supported, in part, by JetBlue, the NFL, and the NFL Players Association.

American Academy of Neurology 2017 Annual Meeting (AAN). Abstracts S7.004 and S9.004. Presented April 23, 2017.

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