Can infections increase Parkinson’s risk?
We discover the latest research on the role of risk factors in Parkinson’s, and delve into the world of infectious risk factors to find out what they could mean for prevention and treatment.
When it comes to the causes of Parkinson’s, often we hear statements like ‘it’s complex’ or ‘the causes are not fully understood’. It may seem baffling that in the 21st century we still cannot pinpoint the cause of the second most common neurodegenerative disease, which affects up to 10 million people worldwide.
As researchers attempt to address this gap in our understanding, the reason we don’t understand what causes Parkinson's is becoming apparent — it is seldom caused by a single factor, instead many contributing factors influence risk. In most cases, these individual factors have a very subtle effect, but when they are combined together in the right way at the right time the effects become substantial.
What are the risk factors for Parkinson’s
Over the course of a lifetime, different people are exposed to different environment, lifestyle and other risk factors and the effects start to add up. But another challenge in identifying the factors that really make a difference comes from the fact that any effects on the brain cells may only become noticeable many years, if not decades, after exposure.
But not all risk factors are detrimental, any single factor may either positively or negatively affect risk and some may even have different effects in different situations. For instance, consumption of fats in the diet has been associated with a reduced risk of Parkinson’s, but a fatty diet has been reported to increase risk marginally only in those who had never smoked, and swapping polyunsaturated fat for saturated fat has been reported to increase risk of Parkinson’s in men but not women.
Similarly, high cholesterol has been linked with lower Parkinson’s risk, but the use of statins complicates matters. As such, there is still more to learn about the association between fat intake, cholesterol and Parkinson’s risk.
While for most individuals it is unlikely that the exact recipe of effects that contributed to the development of the condition will be determined, considerable advances have been made in our understanding over the last 10 years.
This progress has principally been made through extensive longitudinal population studies and the increased availability of large electronic patient databases.
Today, there ever lengthening list of factors we believe can have either a positive or negative effect in Parkinson’s. Those with the greatest Parkinson’s risk increasing effect include age and the presence of certain genetic variants of genes such as PINK1, parkin and LRRK2. Being male is another commonly known risk factor for Parkinson’s as prevalence of the condition is greater in males than females, although the effect size of this factor is much less and the exact reason why this is the case is still up for debate. But it too likely has multiple contributing factors ranging from genetics and hormones, to lifestyle and profession.
Other examples of factors that influence Parkinson’s risk include:
However, it is important to note that the effect of these factors is still very small. For instance, one of the biggest effects is associated with a family history of Parkinson’s, which could increase your risk by around 4 fold, but most of the of other factors that increase risk do so by less that 2 fold. As life time risk of Parkinson’s is estimated at 2.7%, even with a factor that increases risk by 2–4 fold, the risk of developing the condition is still fairly low.
Infections rarely feature in the list of most important risk factors in Parkinson’s. This is because the evidence of any association is more sparse or inconsistent. However, infectious risk factors that may have an association with the condition include measles, hepatitis, influenza, and Helicobacter pylori.
Can you catch Parkinson’s?
Perhaps the most interesting association between Parkinson’s and infection dates back to a worldwide epidemic of encephalitis lethargica, also known as the sleeping-sickness, between 1916 and 1930. During this time, this catastrophic condition is estimated to affected more than a million people worldwide.
The symptoms of encephalitis lethargica started with a high fever, headache, and sore throat and progressed to tremors, muscle pains, double-vision, psychosis and hallucinations, followed by increasing drowsiness and lethargy. Many became comatose and completely unresponsive, but those who recovered often developed a condition known as Postencephalitic Parkinson’s. This caused life-long Parkinson’s-like symptoms such as slowness, tremors, speech problems, and abnormal muscle movement.
Awakenings — a book and film about those who developed sleeping-sickness
The film Awakenings and its respective book, based on genuine cases reported by Oliver Sacks, is a largely accurate account of the condition and is worth investigating if you would like to know more.
Encephalitis itself isn’t an infection, it is an uncommon but serious condition in which the brain becomes swollen causing unpleasant and progressive symptoms that can result in death. The causes of encephalitis include viral infections that have spread to the brain, problems with the immune system and less commonly bacterial or fungal infections.
While we don’t know the exact cause of the epidemic of encephalitis lethargica that followed World War I, one theory is that it was due to a the immune response to a particular type of bacterial infection although some suggest it could be related to the 1918 Spanish flu pandemic.
Since this endemic, sporadic cases of Postencephalitic Parkinson’s have been reported. But today, the consensus is that there not enough evidence that there is an association between other types of encephalitis and an increased risk of Parkinson’s.
Parkinson’s and other infections
So apart from infections that cause encephalitis, what does the research say?
Over the years, there have been many publications on the topic of infection and Parkinson’s risk. Research from the 1980s suggested that childhood measles infection could provide some protective effects and reduce risk , possibly linked with some complex interaction with the 1918 Spanish flu pandemic. This seems to be backed up by more recent research from a Canadian research team reported a slight reduction in risk with childhood infection of red measles, as well as a non significant reduction in risk for mumps and chicken pox. However, other studies have found no positive or negative association between the two. As such, the link between Parkinson’s mumps and chicken pox is currently inconclusive, and more research is needed to fully understand any link with measles.
Other infections where there is currently inadequate evidence of a link with Parkinson's include croup, rubella (German measles) and polio. But there are a number of infections where recent research is providing evidence of a link.
In a study published in 2017 involving over 500,000 Taiwanese people with and without tuberculosis, researchers have discovered a slight but significant increase in Parkinson’s risk linked with this infection. And last year on the blog, we featured some of the latest research from the University of Oxford into a possible association between hepatitis and Parkinson’s:
Does hepatitis increase Parkinson’s risk?
Research has been published that suggests hepatitis infection could increase the risk of Parkinson’s by up to 76%.
Researchers in China have also published an interesting meta- analysis on the association between H. pylori and Parkinson’s. This type of study aims to combine all the available published data available on a topic and use statistics to better understand the size of effect or resolve uncertainties. The results of this study suggest that H. pylori is associated with around a 59% increase in Parkinson’s risk.
Further research, published in Parkinsonism & Related Disorders, supports this association but showed that eradicating the H. pylori infection did not reduce risk — despite this, researchers are still interested in the underlying biology as there is some evidence from small scale studies that eradicating the infection may improve symptoms in Parkinson’s.
The link between flu and Parkinson’s
In epidemiology studies, influenza has previously been associated with an increased risk of other parkinsonisms — conditions that have similar symptoms to Parkinson’s but are not due to the loss of dopamine producing cells in the substantia nigra. Although some research has suggested a potential link between severe influenza and the condition.
Perhaps the most conclusive evidence so far has come from research in the US, which highlighted that the flu may play an important role in the loss of dopamine brain cells in animal models. The team investigated the effect of a particular strain of flu when combined with neurotoxin called MPTP.
This toxin is frequently used in Parkinson’s research as it that permanently causes Parkinson’s like symptoms by specifically targeting the dopamine producing brain cells in the substantia nigra. While today it is used to mimic the motor symptoms of Parkinson’s in animal models, MPTP was first discovered in California following a spate of hospital admissions where patients had become immobile over night.
It transpired that this outbreak was related to a new “synthetic heroin” containing the chemical MPPP, which had hit the streets in the 1980s. In some batches of the recreational MPPP drug, high levels of an unwanted toxin MPTP were present. In those unfortunate to take the tainted drug, the MPTP quickly caused the loss of the dopamine producing cells producing permanent Parkinson’s like symptoms.
So we know that MPTP is bad news, but what the researchers wanted to find out was if influenza infection could predispose the dopamine producing brain cells to being damaged by the MPTP toxin. What they found was the mice infected with the H1N1 strain of flu showed a 20% greater loss of these cells when treated with MPTP. They also showed that this extra effect caused by the combined effects of flu and toxin could be reduced by vaccinating the mice against flu.
What this research shows is that while flu probably doesn’t cause the loss of dopamine producing brain cells directly, it can cause other factors to play a more significant role — this is known as the ‘multi-hit’ hypothesis.
One of the ways flu may be influencing these cells is through inflammation. There is mounting evidence that inflammation plays a role in the start and spread of Parkinson’s, and researchers have previously shown that certain strains of flu can cause inflammation. As such targeting inflammation could be important for stopping of slowing progression. You may have also noticed earlier in this post that the use of anti-inflammatory medications (such as ibuprofen) was in the list of factors that is believed to slightly reduced risk of Parkinson’s, adding support to this strategy.
But, as yet, there is no conclusive evidence that catching flu can increase the risk of developing Parkinson’s in later life. And we don’t know if the results seen in this experiment will be true for other strains of flu, such as those prevalent in the UK at the moment.
Should you worry about catching Parkinson’s
Ultimately you cannot catch Parkinson’s — it is not caused by a virus or bacteria. But, along with many other factors, infections do appear to play a role in risk, although through largely unknown mechanisms.
While it is unlikely that catching an infection will have a dramatic effect on your risk of developing Parkinson’s — there are simply too many positive and negative factors at play, understanding the associations is giving researchers new insights into factors that damage or protect brain cells. Harnessing the power of protective factors, and understanding how to prevent damaging factors from taking their toll on brain cells, is opening the door to new and better treatments that can slow or stop the condition progressing.
In the meantime, if you want to do anything to reduce your risk of developing the condition, or to slow the progression of symptoms if you have already developed it, research suggests the best things you can do is take part in regular exercise.