People who have had their appendix removed may be at an increased risk for developing Parkinson’s disease, according to findings due to be presented at this year’s Digestive Disease Week.
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For the study, which is the largest yet to look at the association, researchers analysed health records available for more than 62 million patients and identified people who had had their appendix removed (appendectomy) and then developed Parkinson’s disease six months later.
Lead author Mohammed Sheriff (Case Western Reserve University) and colleagues found that undergoing appendectomy increased the risk for Parkinson’s by as much as 300%.
‘Scientists around the world have been looking into the gastrointestinal tract’
The appendix has previously been written off as junk tissue or a vestigial organ, with researchers unable to understand any role it may play in the body.
More recently, however, scientists have started to understand the appendix as an immune tissue that is involved in helping the body defend against microbes and regulate bacteria in the gut. The latest understanding is that the organ serves as a type of reservoir for beneficial bacteria in the intestine, enabling bacteria to replenish when supplies become depleted.
It is this potential link between the intestine and appendix that has led researchers to question its association with Parkinson’s, since new insights have suggested that many illnesses arise due to the presence of certain strains of bacteria. In the case of Parkinson’s, a protein called alpha synuclein is thought to be involved.
Recent research into the cause of Parkinson's has centered around alpha synuclein, a protein found in the gastrointestinal tract early in the onset of Parkinson's. This is why scientists around the world have been looking into the gastrointestinal tract, including the appendix, for evidence about the development of Parkinson's.”
So far, such investigations have been inconsistent and reported contradictory findings. Some studies have shown no association between the appendix and Parkinson’s, while one study conducted in Europe found that patients who retained their appendix were more likely to develop the condition.
Another study led by Viviane Labrie at the Van Andel Research Institute in America found that people who had their appendix removed earlier in life were at a significantly decreased risk for developing Parkinson’s disease.
This study, which was published last year in the journal Science Translational Medicine, the researchers analyzed data available for almost 1.7 million individuals whose health information was monitored for up to 52 years.
‘We were surprised’
In the present study, the team found that individuals who had undergone appendectomy were at a 19.3% decreased risk for developing Parkinson’s. In addition, among people who had undergone the procedure and then developed Parkinson’s later, disease onset was delayed, compared with people who still had their appendix.
Among people who had undergone appendectomy at least 30 years previously, the average delay in disease onset was 3.6 years. The researchers also discovered that a toxic form of alpha synuclein had accumulated in the appendixes of healthy individuals. This finding suggested that the appendix could serve as a reservoir for the toxic protein and may play a role in the onset of Parkinson’s.
We were surprised that pathogenic forms of alpha-synuclein were so pervasive in the appendixes of people both with and without Parkinson’s. It appears that these aggregates—although toxic when in the brain—are quite normal when in the appendix.
This clearly suggests that their presence alone in the gut cannot be the cause of the disease.”
These examples of contradictory findings prompted Sheriff and colleagues to investigate the association using data from an Ohio-based company that obtains health record data from 26 integrated health systems.
They discovered that among 488,190 patients who had undergone appendectomy, 4,470 or 0.92% were later diagnosed with Parkinson’s disease. Among the remaining 61.7 million people who had not undergone the procedure, only 177,230 or 0.29% were later diagnosed with the condition.
According to Sheriff and team, individuals who had their appendix removed were at more than a three-fold increased risk for developing the condition, compared with individuals who had not had their appendix removed.
The positive finding was that such a small fraction of either study group went on to develop Parkinson’s disease and that there was no increased risk associated with age group, race or gender. However, the results do imply that appendix removal can more than triple the risk of Parkinson’s developing.
It is also important to note that the findings only point towards a correlation and cannot be considered as evidence that having the appendix removed actually causes Parkinson’s disease. At this stage, researchers still cannot clarify exactly what the relationship between appendectomy and Parkinson’s is.
This research shows a clear relationship between the appendix, or appendix removal, and Parkinson's disease, but it is only an association. Additional research is needed to confirm this connection and to better understand the mechanisms involved.”
What is Parkinson’s disease?
Parkinson’s disease is a neurogenerative condition that affects parts of the brain involved in controlling movement and balance. Symptoms include tremor and shaking of the hands and limbs, rigidity, slowed movement and difficulty maintaining balance.
Symptoms are observed seen when a person tries to engage in an activity such as getting up and walking, which usually results in them moving too quickly or in an uncoordinated manner. Other early symptoms include difficulty swallowing (dysphagia), sleepiness or drowsiness, constipation and a diminished sense of smell.
According to Parkinson's UK, around 127,000 people are affected across the nation, which translates as around one in every 500 members of the general population. The disease is mainly diagnosed at around the age of 60 but about 1 in 20 people are diagnosed at a younger age.
Sheriff, M. Z., et al. (2019). Parkinson's Disease is More Prevalent in Patients with Appendectomies: A National Population-Based Study. doi.org/10.1016/S0016-5085(19)40573-8.