AwesomeCapital: CTE in Pro Football Players: Evidence Piles Up

Thursday, April 11, 2019

CTE in Pro Football Players: Evidence Piles Up

Brain scans indicated that living former National Football League (NFL) players with cognitive and neuropsychiatric symptoms had elevated tau levels in brain regions that are affected by chronic traumatic encephalopathy (CTE), a small study found.

Flortaucipir positron-emission tomography (PET) imaging showed higher amounts of tau in the bilateral superior frontal, bilateral medial temporal, and left parietal regions of 26 former NFL players than controls, reported Robert Stern, PhD, of Boston University School of Medicine, and colleagues in the New England Journal of Medicine.

Currently, CTE can be diagnosed only through postmortem neuropathological examination. “We now have research findings that suggest we can detect the tau PET changes associated with CTE in life,” said study author Eric Reiman, MD, of Banner Alzheimer’s Institute in Phoenix.

“We were able to show small but statistically significant increases in tau depositions, particularly in those regions that were suggested to be preferentially affected by CTE,” Reiman told MedPage Today.

“We were able to show the tau depositions were associated with the [number of] years of football playing,” he continued. “We were not yet able to show a relationship with cognitive or behavioral symptom severity, which might be related to the small number of participants. And we found no elevation in amyloid PET measurements; only one of the NFL players had a positive amyloid PET scan, suggesting their cognitive and behavioral symptoms are not attributable to Alzheimer’s disease.”

CTE is a neurodegenerative disease associated with repetitive head impacts, defined pathologically by the deposition of paired helical filament tau aggregates which are seen initially in the frontal, temporal, and parietal cortices.

“The ostensible chain of events leading to CTE is as follows: playing contact sports, sustaining concussion or other trauma, initiation of events that lead to inflammation or protein misfolding, aggregation of tau protein that leads to degeneration of neurons and supporting elements, and emergence of behavioral and cognitive disturbances years after exposure to play,” wrote NEJM deputy editor Allan Ropper, MD, in an accompanying editorial.

“Stern and colleagues have produced data, now published in the Journal, that in football parlance ‘move the chain,'” Ropper said.

In their research, Stern and co-authors used flortaucipir PET to measure tau and florbetapir PET to assess amyloid-beta in 26 former NFL players with cognitive and neuropsychiatric symptoms and 31 asymptomatic men with no history of traumatic brain injury.

The researchers used automated image analysis algorithms to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore links between SUVR and symptom severity and associations with years of playing football.

Mean flortaucipir SUVR was higher among former players than among controls in three brain regions:

Bilateral superior frontal (1.09 vs 0.98; adjusted mean difference 0.13, 95% CI 0.06-0.20; P<0.001)

Bilateral medial temporal (1.23 vs 1.12; adjusted mean difference 0.13, 95% CI 0.05-0.21; P<0.001)

Left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12, 95% CI 0.05-0.20; P=0.002)

Exploratory analyses showed that the correlation coefficients in these three regions between SUVRs and years of play were 0.58 (95% CI 0.25-0.79), 0.45 (95% CI 0.07-0.71), and 0.50 (95% CI 0.14-0.74), respectively.

The researchers found no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition that were comparable to those in persons with Alzheimer’s disease.

“The risk of CTE associated with a long duration of playing football, hinted at in the current study and in another from the same group, does not necessarily correspond to the number, severity, or serial occurrence of concussions,” Ropper noted. “Individual factors such as the player’s size, head-to-neck configuration, style of play, and position, as well as biologic attributes may influence the deposition of tau.”

While the results of this study provide initial support for flortaucipir PET to detect abnormal tau from CTE during life, “we’re not there yet,” Stern said in a statement. “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.”

The authors are working with other researchers on a longitudinal study called DIAGNOSE CTE to follow former NFL players, former college football players, and people with no history of contact sports play, Reiman added. Initial DIAGNOSE CTE results are expected in early 2020.

The study was funded by grants from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company), the National Institutes of Health, the State of Arizona, and the U.S. Department of Defense. All flortaucipir and florbetapir PET radiotracers were provided by Avid Radiopharmaceuticals.