Neurodegenerative diseases are becoming more common

Every advance in biomedicine that increases life expectancy has an inevitable consequence - it increases the likelihood that that our bodies are going to outlive our brains. Neurodegenerative diseases are becoming far more common. Alzheimer's or other forms of dementia are diagnosed in 1 in 3 deaths of individuals over 65. Neurodegenerative diseases are debilitating because we don't re-grow neurons, which are the basic information processing unit in your brain. As we age, neurons die. They don't grow back. If we promote their death with things like alcohol, toxins, or repeated head trauma then by adding to the circumstances that kill neurons as we age, we increase the likelihood that this will seriously impact our behavior.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease

CTE was first reported as 'punch-drunk' (Martland, 1928), 'dementia pugilistica' (Millspaugh, 1937) and 'the psychopathic deterioration of pugilists' (Courville, 1962). The symptoms are progressive changes in behavior that follow from progressive death of neurons and astrocytes (a type of cell in the brain that supports neurons). Like all neurodegenerative diseases, the loss manifests itself as small changes in behavior that become more pronounced as the disease progresses. Initially, the symptoms are primarily emotional - a person in the early stages of CTE may appear to be depressed or to have bi-polar disorder. Sometimes there is erratic behavior or mania and hallucinations or delusions. As the degeneration progresses, the individuals behavior becomes more erratic and is accompanied by social instability, loss of attention, concentration, and memory; dizziness, headaches, confusion and disorientation. At the end, a full-blown profile of Parkinson's disease emerges as the degeneration reaches brain structures that are important for initiating movement. Abnormalities in movement, gait, and speech are observed and Parkinson's disease may be the clinical diagnosis.

This diagnosis particularly hits home for Charger fans. Junior Seau was one of my favorite Chargers as a kid, but his struggles with depression and his arrest and automobile accident from 2010 seem, in retrospect, like a precursor to his suicide in 2012. I have no doubt there were milder symptoms leading up to the arrest, accident and eventual suicide. That's one of the most annoying things about mental health issues in this country, the social stigma associated with the labels (depressed or addicted or bi-polar) means that the person and their support network tend to ignore the little signs and symptoms until something happens that forces us to acknowledge it. At that point, it may be too late to do anything meaningful in terms of treatment.

The Pathology of CTE

The pathology of CTE is pretty easy to observe. Degeneration results in moderate reductions in brain weight and enlargement of the ventricles, which are the empty places that show up as dark spots in an MRI. As neurons die, ventricles enlarge because there is less tissue constraining the volume of those openings. The atrophy is most prominent in the frontal lobe which regulates emotion and attention, which explains why early symptoms emerge as emotional problems like depression and mania and lack of attention.

After trauma, the neurons themselves become kind of like a tangled-up mass of wires, a feature that also occurs in some Alzheimer's cases. The axon, which is the part of the neuron that sends an electrical signal, becomes twisted and bundles of axons together (what we think of as 'nerves' outside the brain and spinal cord) become entangled - neuropathologists refer to these as 'neurofibrillary tangles'. To avoid dealing with copyright, here is my MS paint protrayal of neurofibrillary tangles. This image is not intended to be humorous, although my artistic abilities definitely leave somthing to be desired:

The parts of your neurons that are sending information become tangled up and damaged, and eventually cause the cells to die. Not pretty.

What's a Concussion

Concussion is the most common form of acute traumatic brain injury. The medical literature usually refers to concussion as MTBI (mild traumatic brain injury). It's hard to define and several definitions are used, but probably the most common is "a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces" (Cantu, 2006). The long and short of it is this - you hit your head hard, may or may not lose consciousness, may or may not have brief losses of memory, and definitely cause some short-term impairment of brain functioning. We used to think of it as mild and reversible disruption, but new evidence is showing that concussion causes diffuse damage to axons (Grahame, 2000), which is probably the result of damage and inflammation or swelling around the membrane of the axon. This is thought to be the pre-cursor to CTE because it could start a biochemical cascade that leads to tangles. I should point out that hitting your head is not physically tangling up your neurons - it's causing the inflammation around the cell membrane and that starts a biochemical process, maybe, that causes the neurofibrillary tangles which are characteristic of CTE. The jury is still out on the specific process that leads to the development of tangles.

Brain Injury and Impact Sports

It's tough to prove a causal relationship between impact sports and CTE because the neuropathology of CTE is also observed in Alzheimer's disease and aging. Also, CTE, like Alzheimer's disease, cannot be diagnosed until after the patient is dead and a pathologist can take a look at the brain. Because of these complications, we only have correlations between impact sports and CTE. I see this debate as similar to the early debate on tobacco use and cardio-pulmonary disease. On the one side you have the people who remind us that associations are just associations, they don't show cause (Big Tobacco). On the other, you have the people asking how much association data do we need before we can infer a causal role (everyone else)? The association findings are mounting. Impact sports are associated with more concussions and more concussions in your lifetime increases the likelihood that you will be diagnosed with CTE post-mortem.

In 2009 there were 51 neuropathologically confirmed cases of CTE, 46 of them were athletes. There were 39 amateur or professional boxers (4-25 years competing), 5 football players (14-23 years competing), a pro wrestler, and a soccer player (McKee, 2009). Half were symptomatic within 4 years of stopping play. Last year, a study showed that NFL players were about 4 times as likely as the general population to be diagnosed with Alzheimer's disease (Lehman, 2012). The two are not unrelated, hopefully I have made that clear. Have no fear, more association data are coming - a google scholar search on "sports and CTE" produced 500 results, since 2012. Not all of them were peer reviewed science, but it's enough interest to be clear that the issue is not going away.

The NFL

For their part, the NFL is taking a much more responsible approach to brain disease than big tobacco took with cardio-pulmonary diseases. Roger Goodell has acknowledged that brain injury and player safety issues are a priority. Goodell announced a $60 million dollar contribution and a partnership with General Electric to promote brain imaging technologies that would aid in the diagnosis of brain injury. The NFL also donated $30 million to the NIH foundation for sports injury research in 2012. This year's rule change penalizing offensive players for leading with the crown of the head is further evidence of the league acknowledging that something does need to be done about impact, even if they aren't saying anything directly about the effect of playing on TBI.

What should change?

Tackling is fun to watch. Fighting is fun to watch (see Hockey and UFC). Speed, is fun to watch. Every sport has horrific moments which make us question the safety of the game and the need for better medical supervision, rule changes, and better protection for the participants. As a brain scientist I am horrified by what I see as a clear causal relationship between repeated impact and brain disease. As a fan, I am passionate about a sport that is so natural and primal - I am almost ashamed to say I love the violence of the game. So how do I resolve this conflict? What, as a fan, do I want to see change to better the game and prevent the athletes from suffering from long-term brain damage?

Remove the conflict of interest from medical staff. The medical staff for each team should be hired and managed by the NFLPA. The folks making medical decisions about player health and safety should be paid by the people who have the interests of the players, not the team, at heart. Anything less is a conflict of interest. $90 million dollars in donations in 2012 is a drop in the proverbial bucket for a sport that had $9.5 billion in revenue in 2012. The NFL should do more than sneeze at the issue, financially speaking. More research on impact reducing equipment, especially helmets and more research on TBI to independent investigators. A brain injury or sports injury foundation seems like a fantastic idea. No more leaving the feet unnecessarily to make tackles. The problem is impact. How do we reduce the effect of impact on the brain? The NHL instituted a rule on checking - no leaving the feet - to try to reduce injuries resulting from our favorite part of hockey - hitting. Now one of Hockey's biggest hitters, Brendan Shanahan, as Director of Player Safety, is tasked with enforcing what is a clean hit and what is not. I think he kind of uses the same approach that the Supreme Court uses to identify what is porn and what is not - "We know it when we see it."

How can we make tackling safer? How can we get players to stop pretending that throwing themselves at a ball carrier has no long term impact on both of their brains? These are just a few ideas. If you made it this far, I am interested to hear yours. There definitely need to be rules limiting impact, because being on Top Plays is nice, but living to a ripe old age with all of your emotions and memories intact may be nicer.

CrimeTime31 is a brain scientist who studies substance dependence and is not an expert in CTE or traumatic brain injury.