November 5, 2018

expert reaction to a study looking at the appendix and Parkinson’s disease

Scientists comment on a study, published in Science Translational Medicine, which shows links between the appendix and Parkinson’s disease.

Prof Tom Foltynie, National Hospital for Neurology & Neurosurgery, UCL Institute of Neurology, said:

“This is strong, highly valuable, long term epidemiological evidence providing further links between gut pathology and the subsequent risk of developing Parkinson’s disease.  The consistency of the findings between two separate large datasets is also strengthened by the reports of abnormal forms of alpha synuclein protein (which causes Parkinson’s disease pathology in the brain) commonly occurring in human appendix specimens.

“The question that remains is why Parkinson’s develops in only some people with abnormal alpha synuclein aggregation in the gut, and why others are seemingly resistant.  An answer to this will help us intervene to prevent those processes linking gut pathology to brain disease.”

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

“This is a competent, thorough study in statistical terms, but there are things that it inevitably can’t tell us.  Using data observed on large groups of individuals, who can differ from one another in so many ways, does make it very difficult to establish what causes what.  People who had their appendix removed in early life will, on average, differ from people who didn’t in several ways.  Any of these differences might be the cause of the decreased risk of Parkinson’s disease in those who had their appendix out, rather than the removal of their appendix.  It’s possible to make statistical adjustments to try to allow for these other differences, and indeed these researchers did that, in different ways, in the two groups of people they studied.  But that can be done only for factors on which the researchers have data.  For instance results showed that, in the Swedish group, adjusting for where people lived (urban or rural) made a considerable difference to the detailed findings – but in the American group, the researchers did not or could not make that adjustment.  Other adjustments were made for the American group, that weren’t made for the Swedish group, quite probably because the researchers did not have the data.  So we just can’t be sure that the reduced risk is actually caused by removal of the appendix in early life – maybe it is, but maybe it isn’t.

“The researchers’ investigations of possible detailed reasons for a link between the appendix and Parkinson’s disease, in terms of the presence of certain proteins in the appendix, does go part of the way to establishing a reason why the relationship between appendix removal and Parkinson’s disease might be one of cause and effect.  As a statistician, I’m not qualified to evaluate all the details of that aspect of the research.  However, it’s still not the case that cause and effect has been established beyond doubt, and the researchers themselves say that they haven’t yet established all the details of what is going on and that their future research will look at other factors.

“This research certainly doesn’t mean that people should be encouraged to go and have their appendix out if there’s nothing wrong with it.  The researchers definitely aren’t suggesting that.  Even if we knew that having your appendix out definitely causes a reduction in Parkinson’s Disease risk – and I’ve explained why we don’t know that yet – any surgery, even routine surgery like appendix removal, carries potentially serious risks to health.  Furthermore, several previous studies have looked for relationships between appendix removal and various other diseases, including heart disease as well as various diseases of the gut.  For some of these diseases, having your appendix out was associated with a reduced disease risk, but in others, including heart disease, it was associated with an increased risk.  These studies were also observational, so again there has to be doubt about whether the appendix removals actually caused the changes in risk – but there’s clearly a balance of risks involved.”

* ‘The vermiform appendix impacts the risk of developing Parkinson’s disease’ by Bryan A. Killinger et al. was published in Science Translational Medicine at 18:00 UK time on Wednesday 31 October 2018.

Declared interests

Prof Tom Foltynie: “I have no relevant conflicts of interest.”

Prof Kevin McConway: “I am a member of the Advisory Committee of the SMC.”