The exact causes of motor neurone disease (MND) are currently not known. It is thought a number of genetic, environmental and lifestyle risk factors need to combine before most forms of MND develop. Together, these risk factors may ‘tip the balance’ towards someone developing the disease. Identifying the factors and how they combine will help researchers discover why the disease starts and potentially find strategies to lower the risk of developing MND.
What is a risk factor?
A risk factor is something that increases the chance of developing a disease. In the case of MND, this could be genetic, environmental or related to a person’s lifestyle. These factors may combine to ‘trigger’ MND but may not be enough to cause MND on their own.
While researchers have identified over 40 genes linked to the development of MND, identifying the environmental and lifestyle factors linked to MND has been more difficult. Many different potential factors have been studied over the years. However, the evidence gained from these studies has often been conflicting and clear conclusions cannot currently be given.
In this blog, we take a look at the evidence so far for some of the risk factors which have been investigated for MND. The links in this blog will take you to published research papers on the topics discussed.
Genetics
Our genes hold the instructions to all the biological processes that happen within our body, including, for some people, the potential to develop MND. For many people with MND, certain genes play a role in the cause of the disease. However, other environmental and lifestyle factors are also thought to be needed alongside these gene changes. Just because someone has a change in a gene, does not guarantee they will develop MND.
In some families, changes in genes can be passed down through generations and play a larger role in the start of the disease. Around 1 in 10 people with MND have a family history of the disease. In these cases, it is thought that genetics is a major contributor to the development of MND, but again other factors alongside the genetic influence are thought to trigger symptoms.
Age and gender
Most people diagnosed with MND are aged between 50 and 70 years old. Research has shown that normal ageing can affect the structure and function of motor neurons. These age-related effects could also play a vital role in development of MND, again, alongside other lifestyle, environmental and genetic factors.
Men are diagnosed with MND almost twice as often as women, but this evens out with people who are 70 or older. It is not clear why the disease affects men more and further research is needed to understand why this is the case and what factors might be driving this.
Lifestyle
The choices we make when living our lives, such as what we eat and if we exercise, can impact our health and the risk of developing different diseases. Some of these lifestyle factors have been investigated to see if they may affect the risk of developing MND. Many of these studies have only looked at a small group of people and some even contradict each other. Therefore, further research is still needed to fully understand which lifestyle factors may play a role in the development of MND.
Exercise
Several studies have investigated a potential link between strenuous exercise and MND. But what is strenuous exercise? Each of these studies had a different definition, with some classing it as playing professional rugby or football, others classed it as frequent and intense, anaerobic bursts of activity. While each definition differs, there is still no clear answer. Some studies found that really high levels of intense exercise may be linked, while others did not. The studies which did suggest a link had limitations, such as only looking at a small number of people.
Many researchers investigating whether exercise is linked to MND still state that the benefits of exercise, such as reducing the risk of cardiovascular disease, far outweigh any potential risk.
Head Trauma/Injury
One theory behind the potential link between exercise and MND is that people who play contact sports, such as football and rugby, are more prone to head injuries. Research has suggested that traumatic brain injuries are a risk factor for a number of neurodegenerative conditions, including dementia.
Current research investigating head injury and MND is conflicting, with some studies suggesting an increased risk, while others show no links between head injuries and MND.
Smoking
A small number of studies have hinted that smoking may increase the risk of developing MND. In one study, no overall change in risk was associated with smoking, but when participants were grouped by their sex, women who had smoked showed a potential greater risk. Theories around how smoking may influence MND risk, include motor neuron damage from chemicals found in tobacco and that smoking is thought to cause oxidative stress and inflammation.
Military Service
There have been several studies in the United States which suggested people who served in the military have a higher risk of being diagnosed with MND. Another study, in the UK, also identified an increased risk for veterans compared to non-veterans. However, the researchers were keen to highlight that the overall risk was extremely low.
Both studies found the increased risk was seen across different conflicts and deployments, potentially ruling out any specific environmental exposure from a particular deployment. The length of service in the military was also found to not increase the risk. Researchers have also mentioned that other lifestyle factors cannot be ruled out as the potential reason for this increased risk. This includes smoking, as there are higher rates of smoking in military personnel, and trauma.
Environmental Factors
Exposures to substances where we live, or work have been linked to increasing the risk of developing a range of different diseases. Researchers have also looked for a link between environmental exposures and MND. As with lifestyle factors, researchers are still not certain which exposures increase the risk of developing MND and further research is needed.
Exposure to blue-green algae
Blue-green algae is a type of bacteria (called cyanobacteria) which naturally occurs in lakes, rivers and the sea. Some types of blue-green algae can produce toxins which are harmful to humans.
There has been a significant amount of research investigating a link between blue-green algae and neurodegenerative diseases. However, there still isn’t a clear scientific consensus on whether it does increase the risk or not.
Researchers have theorised that a toxin produced by blue-green algae, called beta-methylamino-L-alanine (BMAA), could play a role in the development of MND. One study found that BMAA tricks human cells into thinking it is one of the building blocks of our bodies and this creates faulty proteins. Another study found that BMAA ingestion caused nerve damage like the damage seen in the early stages of MND. This research provides some evidence of how BMAA could behave in the body and potentially trigger MND, but further research is still needed to confirm if BMAA exposure is linked to MND.
Exposure to heavy metals
Heavy metals, such as lead, mercury and arsenic, can be toxic to humans. Exposure can come from working with metals, air or water pollution, some medications and eating lots of food that may contain metals due the environment it comes from (such as fish). Tiny (microscopic) molecules of metals can accumulate in the body after exposure, which can prevent our cells from performing properly. High exposure to heavy metals can lead to heavy metal poisoning and can damage vital organs, such as the brain. This has led researchers to think there may be a link between heavy metal exposure and the development of MND.
Current research into the link between heavy metal exposure and MND is conflicting. To provide more evidence, researchers have investigated how heavy metals may affect the biological processes known to occur in MND. One study found lead contributed to the build-up of a protein called TPD-43, which is found in 97% of all MND cases. However, there is no conclusive evidence, at the moment, to suggest heavy metal exposure increases the risk of developing MND.
Why is it so hard to find the causes of MND?
MND is a very complex disease. It is thought that the disease can be active within the body for a long time before physical symptoms appear. Therefore, what someone may think is a trigger, as it happened close to when symptoms first occurred, might not actually be.
Identifying causes of a disease is also difficult because the only way to know without any doubt that something causes a disease is to expose the person to a specific factor while controlling the other aspects of their life. This is not ethical or possible to do, especially when a disease may take many years to develop after being exposed to the trigger.
Instead, researchers will often use surveys to help identify factors which may increase the risk of developing of the disease. These surveys have the potential to lead to inaccurate results as they rely on people remembering potential factors. People with the disease often want to understand why they developed it, and this may mean that they are more likely to say that they were exposed to a specific factor, even if this is actually not the case. This means that results from survey studies can only provide evidence that a specific factor is linked to the development of the disease, known as correlation, and cannot say that the factor causes the disease.
What does all of this mean for me?
At the moment, only genetics, age and gender have been confirmed as risk factors for MND. However, researchers believe that a combination of factors are needed to ‘trigger’ the development of MND. Unfortunately, researchers are still not sure what all of these factors are, or the combination of factors needed to ‘tip the balance’ towards the disease. More research is currently ongoing to learn more about MND risk factors. In the future this may help provide guidance on how to reduce the risk of developing MND.
You can find out more about genetics and how it can be involved in the development of MND in our next blog.
