Study Find Brain Damage in Former NFL Players

Until now, we couldn’t see evidence of chronic traumatic encephalopathy until autopsy.

If you happen to be reading this on a Sunday, Monday, or Thursday and live in the United States, there’s a good chance you’re watching NFL football tonight.  20 million people on average tune into these games, myself included. Go Eagles. It was my wife who captured why, I think – football players are simply the best athletes out there in terms of all around ability – strength, speed, power, and so on.

But of course there’s something else that draws us to these games – something a bit more primal – it’s, for lack of a better word, the hits. The tackles, the sacks, the bone-crunching collisions.

But it’s hard to fully enjoy the games if you’ve done a bit of reading into chronic traumatic encephalopathy – CTE – and the effect these collisions have on the individuals who play professional Football.

A recent autopsy study out of Boston University examined the brains of 376 former NFL players. 345 of those brains had evidence of CTE – that’s 92%. 

Of course there is selection bias at play here – NFL players who donate their brains to science after their death are likely to do so for a reason. But it is getting pretty hard to deny there is a clear link between NFL play and what amounts to brain damage, at least qualitatively.

The problem with the diagnosis of CTE is that, at least for now, it can only be determined after death. Detecting CTE on autopsy is less than ideal for identifying potential treatment strategies, so I was excited to see a new study leveraging the power of PET MRI to identify brain injury in NFL players who are still alive.

MRI and Autopsy images of CTE-affected brain. Source: Alosco et al. Alzheimer’s Research and Therapy, 2021.

To introduce you to this study, appearing in JAMA Network open I first need to introduce you to an 18 kilodalton protein called translocator protein or TSPO.

TSPO used to be known as the peripheral benzodiazepine receptor as it was found to bind diazepam – but that does not seem to be central to its purpose.

Rather, it lives on the surface of mitochondria and seems to be a very sensitive marker of inflammation and repair. When tissue is damaged TSPO is upregulated, and you can see that upregulation in a PET scan using a selective tracer chemical.

OK, with that background, we can understand the JAMA Network Open study. Researchers led by Jennifer Coughlin at John’s Hopkins enrolled 27 individuals, all of whom had played in the NFL in at least the past 12 years. The average duration of play had been about 6 years. There were 14 linemen, 9 linebackers, 2 wide receivers and 2 kickers.

To serve as controls: 27 elite swimmers – a non-contact sport unless you’re doing it wrong – all of whom had at least been in NCAA division III or higher programs.

After subjecting both groups to a battery of neuropsychiatric tests, they underwent a PET-MRI scan. And the findings are pretty stark.

Across the board, you see higher TSPO levels in the former NFL players. Again, this is indicative of injury, repair, or both. This was a global phenomenon, basically in every region of the brain examined.

Source: JAMA Network Open

Quantitating the levels of TSPO anatomically, you can see significantly more damage and / or repair in the frontal cortex, cingulate cortex, and hippocampus, which is consistent with autopsy CTE results.

Source: JAMA Network Open

The NFL players did similarly to the swimmers on cognitive tests, with the notable exception of tests of learning and memory. The NFL players also had much more variability in their scores than the swimmers, suggesting, not surprisingly, that NFL play likely affects different players differently.  I was hoping to see some comparison of the kickers to the rest of the team, but we were not provided with that data.

The authors note that the performance on the cognitive tests were NOT correlated with the degree of TSPO activation in the NFL players. So yes, overall NFL players had more TSPO, and yes, overall NFL players had worse memory scores, but it wasn’t the same NFL players who had both issues.  So this new scan is not a slam dunk for all that ails the NFL player’s brains.

In a macabre way, we may not really know the value of these scans until much later – when it becomes clear that these players are or (hopefully) are not suffering from dementia, and, even later, on autopsy.

But I am hopeful that, if not this particular diagnostic test, we will make progress on some diagnostic test to identify the harbingers of CTE in the living. Without that, treatment is just a pipe dream.

A version of this commentary first appeared on Medscape.com.