Is Appendectomy Linked to Parkinson’s Disease?

Parkinson’s disease is a neurodegenerative disorder clinically characterized by resting tremor, bradykinesia (slow movements), dyskinesia (impairment of movement), dystonia (stiffness of muscles including facial muscles), a stooped posture, sexual and urinary dysfunction, drooling, and in some cases psychiatric symptoms including psychosis, dementia, and depression.

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Pathologically, dopaminergic neurons in the substantia nigra (striatum) progressively degenerate with time to cause the symptoms and contain protein aggregates of alpha-synuclein that form Lewy bodies. These aggregates are also seen in the gastrointestinal tract earlier on in disease-course and may play a key role in the onset of Parkinson’s disease.

The Appendix, Appendicitis, and Appendectomy

The vermiform appendix (or simply the appendix) is a blind-ended tube that is connected to the caecum or the pouch within the abdomen that signals the start of the large intestine.

The appendix is widely thought to be a vestigial organ or an organ that has lost most of its original function over time. It is thought that the appendix in humans may be enriched with bacterial populations that can quickly repopulate the large intestine after a bout of illness.

The inflammation of the appendix is known as appendicitis that typically clinically manifests as pain in the middle of the abdomen that travels to the lower right side and may become severe.

Other symptoms may include a loss of appetite, nausea, constipation or diarrhea. Appendicitis can lead to life-threatening complications and as such needs to be treated as a medical emergency.

Treatment of appendicitis is usually performed by the removal of the appendix, known as appendectomy. This procedure has excellent success rates and is carried out as a laparoscopy. The cause of appendicitis is still unclear but may be due to blockages of the entrance of the appendix.

The reason why appendectomy is so successful is that the full removal of the appendix is safe for humans with no known long term ill-effects, hence the notion that the appendix is a vestigial organ.

Is There a Link Between Appendix Health and Parkinson’s Disease?

A study published in Science Translational Medicine in 2018 by Killinger et al found that appendectomy was associated with a lower risk of Parkinson’s.

In this study, 1,698,000 people’s health records were investigated, and they found that appendectomy led to a 19.3% reduced cumulative incidence of Parkinson’s disease between controls and those who have had appendectomies.

Furthermore, those that developed Parkinson’s who had appendectomies had greater survival provability (i.e. higher age of diagnosis compared to controls). In this study, biopsy samples of appendices revealed that the healthy human appendix contains truncated forms of pathologically-associated alpha-synuclein fragments, the main pathological hallmark of Parkinson’s that form Lewy bodies. As such, the removal of the appendix may, therefore, delay the onset of Parkinson’s due to the reduction in alpha-synuclein fragments.

This is supported by a study by Mendes et al (2015) who investigated a smaller cohort of 295 patients who found that patients with late-onset Parkinson’s with appendectomy had more years without Parkinson’s than those without. This was not the case for younger-onset patients, however.

Other studies have not found such a strong correlation between appendectomy and delayed onset of Parkinson’s. Yilmaz et al (2017) examined 1625 patients retrospectively and found that appendectomy did not affect the emergency and clinical features of Parkinson’s.

This is supported by another study by Marras et al (2016) who investigated nearly 43,000 individuals undergoing appendectomy and also found that appendectomy did not appear to be associated with a reduced risk of developing Parkinson’s disease.

One study published in 2019 by Sheriff and colleagues found the opposite of the already published literature.

They examined data from around 62 million patients. The overall risk of developing Parkinson’s with appendectomies was 3.19 compared to those without appendectomies. This was irrespective of age, gender, and race. However, this study did not examine the period between appendectomy and the onset of Parkinson’s disease.

As with all of these studies, only correlation can be assumed and not causation. These were all retrospective epidemiological studies based on health records, and whilst they were all age, sex, gender and matched for other parameters, complete control cannot be achieved.

Summary

There is conflicting evidence as to whether appendectomy can increase the risk of developing Parkinson’s disease. In this article, two major contradictory reports were discussed; one by Killinger (2018) showing a reduced risk of Parkinson’s with appendectomy, and the other by Sheriff (2019) showing an increased risk of Parkinson’s with appendectomy.

The relationship between gut health and Parkinson’s is now well established, therefore scientists have turned to look at the role the appendix may play in disease pathogenesis. Despite the contradictory results, it does appear the appendix, healthy or inflamed, may play a role in Parkinson’s onset.

Much more research is needed to elucidate the exact function of the appendix in both health and disease, and especially whether its removal can alter the risk of developing Parkinson’s.

Whilst appendectomies may not alter the total incidence of Parkinson’s, or lead to a higher prevalence (Sheriff, 2019), some studies have shown that appendectomy may increase the time of onset of Parkinson’s disease (Killinger, 2018 & Mendes, 2015).

Further Reading

• All Parkinson's Disease Content
• What is Parkinson’s Disease?
• Parkinson’s Disease Pathophysiology
• Parkinson’s Disease Diagnosis
• Parkinson’s Disease Treatment

Written by

Osman Shabir

Osman is a Neuroscience PhD Research Student at the University of Sheffield studying the impact of cardiovascular disease and Alzheimer's disease on neurovascular coupling using pre-clinical models and neuroimaging techniques.