Discussing the Link Between Concussion and Neurodegenerative Diseases

This post is by guest blogger Matthew Savage 

With approximately 1.4 million people attending A&E every year in the UK with a recent head injury, and with head injury being the biggest cause of death and disability in the under 40s age category, there is no doubt head injury has a severe impact on the UK population (NICE, 2014). In recent years, the association between concussions and neurodegenerative diseases has been of great interest to the scientific community, especially considering between 33% and 50% of the 1.4 million visitors to A&E are under the age of 15 years old (NICE, 2014). In the USA, contact sports such as American Football have come under fierce pressure to protect young players from the risks of repeat concussions due to the fears they can lead to neurodegeneration. The same pressure has been seen in the UK, with the Football Association introducing rules to ban heading during training for children under the age of 11 years old. So why is there concern over the effects of concussion and how can concussion lead to neurodegeneration?

What is concussion?

Traumatic brain injuries can vary from mild to moderate to severe, of which concussion is often classed as a mild traumatic brain injury (mTBI). Concussion is defined as a sudden jolt or blow to the head which leads to transient disturbance of brain function and this leads to inflammation (Harmon et al, 2012). It is a functional, rather than a structural injury (Romeu-Mejia, 2019), and can lead to symptoms of headaches, dizziness, nausea, memory loss and a loss of consciousness. Falls, sporting collisions and road traffic accidents are the primary causes of concussion and the possibility that head injury may predispose a person to developing Alzheimer’s and other neurodegenerative disease and has significant social and medical implications (Li et al, 2017) because of its prevalence in the world population.

What is a neurodegenerative disease?

Neurodegenerative diseases are characterised by progressive damage to neurons in the brain, leading to a number of varied disabilities. For example, Alzheimer’s disease is a neurodegenerative condition characterised by neuronal cell loss, protein plaques consisting of a peptide called amyloid-beta and neurofibrillary tangles consisting of a protein called Tau. Dr. David Nguyen, a neurologist at Pali Momi Medical Centre notes; “These plaques in turn slow down your brain’s ability to store memory and eliminate toxic chemicals your brain makes, eventually damaging your nerves”.  This accumulation can lead to dementia, a state of confusion whereby individuals struggle with recall issues, impairments to memory functioning, attention, language deficits and this can all lead to dramatic personality changes that can be devastating for the individual and their families (Purves et al, 2018). Other neurodegenerative diseases include Parkinson’s disease, Motor neurone diseases (MND) and Huntington’s Disease (HD).

So what is the association between concussion and neurodegeneration?

The symptoms of concussion usually last no longer than two weeks, but increased levels of stress whist still recovering (such as returning to sporting activity too early) can lead to post-concussion syndrome, a situation whereby brain chemistry has been altered, leading to prolonged symptoms. Animal and human studies support the concept of post-concussive vulnerability, showing that a second blow before the brain has recovered results in worsening metabolic changes within the cell. The risk of long-term effects also increases dramatically with repeat concussions, something which has been heavily linked to a condition called Chronic Traumatic Encephalopathy (CTE), a neurodegenerative disease caused by repeat blows to the head. CTE is strongly characterised by deposits of Tau protein, the hallmark of Alzheimer’s disease, with Beta-Amyloid proteins also found in high levels. Several studies have found that repeated concussions increase one’s risk of developing neurodegenerative diseases. For example, one study published in the Journal of American Medicine (2017) found that 99% of brains obtained from deceased NFL players suffered from CTE. Autopsies performed on the former NFL players found evidence of nerve damage and similar results were seen in other brains of players who only played college football. Another study of 7676 ex-Scottish Football players found that ex-players were 5 times more likely to suffer from dementia compared to the control group (MacKay et al, 2019). This link between repetitive concussions, CTE and the similarities in symptoms with Alzheimer’s suggests that neurotrauma increases the risk of developing dementia and accelerates the progression of disease (Turner et al, 2016).

Dr. Nguyen explained that concussions can lead to changes in the brain’s neuro chemicals and damage to the nerves on a microscopic level, leading to neurodegeneration. Even a single, mild TBI can lead to apoptosis (cell death) but, with time to recover, the brain will return to pre-accident levels. However, multiple hits to the head can lead to something known as the “cascade effect”, whereby changes in brain chemistry occur and the hallmark protein abnormalities of Alzheimer's occurs. These can develop within 2 hours of sustaining a TBI. As Dr Cullum (2020) notes; “Concussion can act like a trigger to degenerative changes that stick with you, much like Alzheimer’s”. According to an interesting study by Crane and colleagues (2016), an association between TBI and increased risk of Lewy body accumulation and deterioration of patients with Parkinson’s Disease was found. An increasing body of evidence suggests that a history of TBI puts people at risk in the future.

So why is it important that this link is considered?

It is important to consider the link between concussion as a mild traumatic brain injury and neurodegenerative diseases for a number of reasons. When comparing the two, there are many promising compounds being discovered that appear to be present in both concussive injuries and neurodegenerative diseases. These give great opportunities for producing treatments for both concussion and AD and future research should focus on the roles of Amyloid and Tau as these seem to offer the best chance for a targeted treatment and correction in both conditions. The more we know about the causes of neurodegenerative diseases is also vital, considering over 850,000 people already suffer with dementia in the UK (Alzheimer's Society, 2019) and this is set to increase due to an aging population. The more we know, the greater chance we have of a targeted treatment.

In addition to this, there are discrepancies between findings on the association between concussion and neurodegeneration because of other factors that contribute to neurodegeneration. These include a person’s age, gene expression and other lifestyle factors. For example, one study found that 60% of people who exhibited the APOE 4 Gene suffered from neurodegenerative diseases after the age of 75 years old, compared to just 20% of people in the cohort of individuals without this particular gene. Those with Gene APOE 4 expression were far more likely to be diagnosed with Alzheimer’s than those without the Gene expression (Jordan, 1997). Clearly, even single concussions appear to pose more risk for those who have this gene expression, and this is very useful to know as it means that certain individuals may be more likely to suffer neurodegeneration following just one concussive event. Those most at risk could be identified earlier and targeted prevention measures could be taken. For example, those with the Gene may require longer rest periods following any concussion sustained to ensure no cascade effect occurs or future prospective treatments through national health services could be given to those most at risk. The more we know about these links the better equipped we are to battle these terrible diseases.

About Matt Savage

Matthew Savage has an MSc in Psychology, is a qualified personal trainer, and has worked within the field of cognitive rehabilitation for 5 years. He is an FA qualified football coach, with a keen interest in moral behaviour and wellbeing within team sports. Matthew is also one of our Mental Health Triage Practitioners. 

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