Killing Themselves for Our Entertainment: The NFL and CTE
- Thread starter mascho
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Great job, Dave. It's short but sweet and shines the light on a point that doesn't get enough attention: that these "scandals" are likely interconnected. It also makes me wonder how much of "football culture"—in particular the violence off field—in some respects may be due to head trauma. There's a chicken or the egg factor at work here.
Van Everyman said:
Thanks, VE.
I also want to credit Rev, mabrowndog, ScubaSteve, Mark, Chuck and the entire FC staff for making this piece much more than it was at first draft. Teamwork is a wonderful thing and something I'm very thankful for today.
As for the article...it is something I am wondering about a lot. While I also believe domestic abuse to be a huge problem and something in desperate need of attention, the thought that the NFL is happy to have the domestic abuse scandal plagues me. At least there, something can and supposedly, is being done to address some of the fundamental issues.
Whereas football fans, at least myself, have let the much more troublesome issue of brain injuries slip our attention. Because it is difficult - and because it may put an end to the sport I love.
I'm going to apologize in advance for this post. I apologize for offending any author in the study, or anyone who knows the authors. For anyone who knows me in my professional work, I tend to be a bit critical when it comes to experimental design and hypothesis testing.
I'm also going to apologize if I get a bit sciency here. Feel free to ask me any questions if you need a clarification. I only had about an hour or so to read and write this critique.
Took me awhile to find the article. As with many neuroimaging studies, the article itself is quick and dirty and doesn't really have any strong conclusions at all.
As well summarized by the centralSOSH piece, the authors of the article are using a novel Positron Emission Tomography (PET) scan to see whether it can identify brain abnormalities in aging NFL players that are consistent with chronic traumatic encephalography (CTE).
For those who do not know, PET is an imaging technique that allows us to measure brain structure and activity. PET works by measuring the decay of radioactive substances. For example, if someone wanted to measure changes in brain activity due to some task; one way to infer changes in brain activity is to examine changes in the concentration of glucose in the brain; if glucose increases within a brain region, neurons within the region must have increased their firing rates. One can measure this change in a person or animal by having the person or animal ingest glucose that has a radioactive component attached (e.g. a radioactive ion of fluoride) to it. Since most glucose is present in the brain, the radioactively-bound glucose will be taken into the brain. By measuring the decay in the radioactive fluoride, we can see where this glucose becomes concentrated in the brain (and thereby infer changes in brain activity).
CTE is an odd neurological disorder. It can only be diagnosed in people with a history of concussions or physical trauma to the head, however, the behavioral symptoms are similar to post-concussive syndrome. Unlike PCS, CTE ultimately results in neural degeneration in subcortical regions (such as the hippocampus and amygdala) and cortical regions (frontal and temporal lobes, in particular the mesial temporal lobe), this degeneration is similar to what is seen in other dementias FTD, or AD.
In this case, the authors used a novel drug for PET imaging called FDDNP to examine differences in binding between NFL retired players and healthy controls. DDNP is essentially a protein that binds to amyloid beta and tau. In many forms of dementia (e.g. Alzheimer's disease), amyloid beta deposits into plaques, while tau phosphorylation is related to the formation of neurofibrillary tangles (NFT). Unfortunately, the presence of plaques and tangles is not particularly specific to a single type of dementia. Several types (fronto-temporal dementia, CTE, AD) of dementia have NFT and SPs as hallmarks of the disorder. Furthermore, plaques and tangles can occur in people who are at risk for dementia, despite a complete absence of other psychological or physiological symptoms. As you can imagine, this makes using FDDNP as a diagnostic extremely tricky.
The authors compared 5 retired NFL players with mood/cognitive problems with 5 healthy controls. They found increased expression of FDDNP in subcortical regions and not in cortical regions, which demonstrates elevated levels of neuropathology in the NFL players. To me, this is really interesting and probably the most thought-provoking part of the article. It is possible that the progression of plaques and tangles may be able to dissociate CTE from other forms of dementia; most other dementias may start in the basal ganglia, the mesial temporal lobe, or the posterior cingulate cortex. The authors then claim that the level of FDDNP may be related to the number of concussions each player has had, which is garbage (see below).
However, the article remains flawed for multiple reasons. The first (and largest) is that the sample size here is miniscule. In the neuroimaging field, this is the almost-literal equivalent of determining Xander Bogaerts true talent from his first four PAs in MLB. While promising, one cannot draw any conclusions about whether FDDNP can dissociate between CTE and healthy aging.
Worse, some of these subjects are at an age where they are at risk for other dementias; it is unclear whether the differences in the PET images resulted from the concussions, from putative CTE, were present before any trauma, or resulted from other dementias. While concussions may be necessary for a CTE diagnosis, they are not sufficient; plenty of people have concussions with no early-onset neurodegenerative disorder. To date, I have not a seen a study demonstrating that FDDNP differentiates between healthy people with a history of concussions and people with dementia and a history of concussions. Given that the study here did not control for the number of concussions in their healthy controls, count me as skeptical.
Speaking of concussions, the supposed relationship found between concussions and FDDNP binding is tenuous at best, and disingenuous at worst. One of the subjects is an outlier with 20 concussions, who is 73 years old and has been in a coma. If one were to remove that person from the five, no relationship is observed for amygdala, thalamus, caudate, or putamen. Again, due to the small sample size, we should not make any inferences regarding the relationship between trauma severity and FDDNP binding.
The differences in binding between controls and NFL players are interesting, but also difficult to make conclusions on. It is possible that the FDDNP binding represents a risk-factor for CTE. It has been shown repeatedly and in larger samples that people who are at risk for dementia show increased FDDNP binding in cortical and subcortical regions (depending on the nature of the risk factor). Of course, such information would be extremely valuable to a person deciding whether to play contact sports or join the military.
To conclude, this study provides a promising potential method for examining putative CTE or at-risk factors for CTE. However, future longitudinal studies are required in order to test whether this method works. To infer from this study that concussions cause CTE, or that NFL players are at greater risk for CTE is improper, given the limited sample size, the lack of specificity for behavioral/physiological symptoms, and the limited knowledge we have of FDDNP itself.
It's a shame really. A simple longtidunal study could theoretically evaluate the risk factors present in NFL players for CTE, the progression of putative CTE, and biomarkers specific to CTE. All one would have to do is recruit 30 NFL players and 30 healthy controls, and perform one-year assessments which includes a full cognitive/psych battery, an FDDNP-PET scan, and a 3-hour MRI session. This would cost pessimistically 30,000 per person per year, or 1.8 million per year in direct costs; probably about 6 million when you include the indirect costs. I'm pretty sure the NFL has the money to bankroll such a study.
EDIT: I just want to emphasize again, that there are some things the NFL can do to address issues underlying neurological disorders in NFL players. Funding research into diagnosing and treating said disorders is one of them, and isn't expensive relative to what the NFL spends on everything else.
I'm also going to apologize if I get a bit sciency here. Feel free to ask me any questions if you need a clarification. I only had about an hour or so to read and write this critique.
Took me awhile to find the article. As with many neuroimaging studies, the article itself is quick and dirty and doesn't really have any strong conclusions at all.
As well summarized by the centralSOSH piece, the authors of the article are using a novel Positron Emission Tomography (PET) scan to see whether it can identify brain abnormalities in aging NFL players that are consistent with chronic traumatic encephalography (CTE).
For those who do not know, PET is an imaging technique that allows us to measure brain structure and activity. PET works by measuring the decay of radioactive substances. For example, if someone wanted to measure changes in brain activity due to some task; one way to infer changes in brain activity is to examine changes in the concentration of glucose in the brain; if glucose increases within a brain region, neurons within the region must have increased their firing rates. One can measure this change in a person or animal by having the person or animal ingest glucose that has a radioactive component attached (e.g. a radioactive ion of fluoride) to it. Since most glucose is present in the brain, the radioactively-bound glucose will be taken into the brain. By measuring the decay in the radioactive fluoride, we can see where this glucose becomes concentrated in the brain (and thereby infer changes in brain activity).
CTE is an odd neurological disorder. It can only be diagnosed in people with a history of concussions or physical trauma to the head, however, the behavioral symptoms are similar to post-concussive syndrome. Unlike PCS, CTE ultimately results in neural degeneration in subcortical regions (such as the hippocampus and amygdala) and cortical regions (frontal and temporal lobes, in particular the mesial temporal lobe), this degeneration is similar to what is seen in other dementias FTD, or AD.
In this case, the authors used a novel drug for PET imaging called FDDNP to examine differences in binding between NFL retired players and healthy controls. DDNP is essentially a protein that binds to amyloid beta and tau. In many forms of dementia (e.g. Alzheimer's disease), amyloid beta deposits into plaques, while tau phosphorylation is related to the formation of neurofibrillary tangles (NFT). Unfortunately, the presence of plaques and tangles is not particularly specific to a single type of dementia. Several types (fronto-temporal dementia, CTE, AD) of dementia have NFT and SPs as hallmarks of the disorder. Furthermore, plaques and tangles can occur in people who are at risk for dementia, despite a complete absence of other psychological or physiological symptoms. As you can imagine, this makes using FDDNP as a diagnostic extremely tricky.
The authors compared 5 retired NFL players with mood/cognitive problems with 5 healthy controls. They found increased expression of FDDNP in subcortical regions and not in cortical regions, which demonstrates elevated levels of neuropathology in the NFL players. To me, this is really interesting and probably the most thought-provoking part of the article. It is possible that the progression of plaques and tangles may be able to dissociate CTE from other forms of dementia; most other dementias may start in the basal ganglia, the mesial temporal lobe, or the posterior cingulate cortex. The authors then claim that the level of FDDNP may be related to the number of concussions each player has had, which is garbage (see below).
However, the article remains flawed for multiple reasons. The first (and largest) is that the sample size here is miniscule. In the neuroimaging field, this is the almost-literal equivalent of determining Xander Bogaerts true talent from his first four PAs in MLB. While promising, one cannot draw any conclusions about whether FDDNP can dissociate between CTE and healthy aging.
Worse, some of these subjects are at an age where they are at risk for other dementias; it is unclear whether the differences in the PET images resulted from the concussions, from putative CTE, were present before any trauma, or resulted from other dementias. While concussions may be necessary for a CTE diagnosis, they are not sufficient; plenty of people have concussions with no early-onset neurodegenerative disorder. To date, I have not a seen a study demonstrating that FDDNP differentiates between healthy people with a history of concussions and people with dementia and a history of concussions. Given that the study here did not control for the number of concussions in their healthy controls, count me as skeptical.
Speaking of concussions, the supposed relationship found between concussions and FDDNP binding is tenuous at best, and disingenuous at worst. One of the subjects is an outlier with 20 concussions, who is 73 years old and has been in a coma. If one were to remove that person from the five, no relationship is observed for amygdala, thalamus, caudate, or putamen. Again, due to the small sample size, we should not make any inferences regarding the relationship between trauma severity and FDDNP binding.
The differences in binding between controls and NFL players are interesting, but also difficult to make conclusions on. It is possible that the FDDNP binding represents a risk-factor for CTE. It has been shown repeatedly and in larger samples that people who are at risk for dementia show increased FDDNP binding in cortical and subcortical regions (depending on the nature of the risk factor). Of course, such information would be extremely valuable to a person deciding whether to play contact sports or join the military.
To conclude, this study provides a promising potential method for examining putative CTE or at-risk factors for CTE. However, future longitudinal studies are required in order to test whether this method works. To infer from this study that concussions cause CTE, or that NFL players are at greater risk for CTE is improper, given the limited sample size, the lack of specificity for behavioral/physiological symptoms, and the limited knowledge we have of FDDNP itself.
It's a shame really. A simple longtidunal study could theoretically evaluate the risk factors present in NFL players for CTE, the progression of putative CTE, and biomarkers specific to CTE. All one would have to do is recruit 30 NFL players and 30 healthy controls, and perform one-year assessments which includes a full cognitive/psych battery, an FDDNP-PET scan, and a 3-hour MRI session. This would cost pessimistically 30,000 per person per year, or 1.8 million per year in direct costs; probably about 6 million when you include the indirect costs. I'm pretty sure the NFL has the money to bankroll such a study.
EDIT: I just want to emphasize again, that there are some things the NFL can do to address issues underlying neurological disorders in NFL players. Funding research into diagnosing and treating said disorders is one of them, and isn't expensive relative to what the NFL spends on everything else.
One additional point on the science side: while tau tangles co-occur with CTE and other brain diseases, it is not clear that they cause disease. They may be harmful, or they may be a sign of a normal or neuroprotective cellular process that is trying to fight off the badness.
I also suspect that when we have a good test for Alzheimer's we will extend that to develop a good test for CTE - there is so much more money going into Alzheimers I think that will be successful before the small PET CTE studies.
Nice article. It'll be interesting to see what happens to football in ten years.
I also suspect that when we have a good test for Alzheimer's we will extend that to develop a good test for CTE - there is so much more money going into Alzheimers I think that will be successful before the small PET CTE studies.
Nice article. It'll be interesting to see what happens to football in ten years.