Four gut disorders associated with increased Parkinson’s risk
A new study has found that particular gastrointestinal disorders are associated with an increased risk of developing Parkinson’s disease. The research provides further evidence to support the hypothesis that the neurodegenerative disorder begins in the gut.
One of the hallmarks of Parkinson’s disease (PD) is thought to be the abnormal deposition of Lewy bodies, made up mostly of the toxic misfolded protein alpha-synuclein, not only in the central nervous system but also in the enteric nervous system, which controls the gastrointestinal tract.
That these deposits could be found in both places led German anatomist Heiko Braak and his colleagues to hypothesize that PD begins when a foreign agent enters the body via the nose or gastrointestinal system and travels into the central nervous system via the vagus nerve. While Braak’s hypothesis remains divisive, previous studies have supported it. Now, researchers from the Mayo Clinic in Arizona have undertaken a large-scale study to test the hypothesis, investigating the association between gastrointestinal conditions and the risk of developing PD.
The researchers used data from TriNetX, a nationwide network of US electronic medical records, to compare 24,624 people who’d been diagnosed with PD of unknown cause with those who’d been diagnosed with other neurological conditions such as Alzheimer’s disease (19,046) or cerebrovascular disease (23,942), and a comparison group of 24,624 with none of these conditions.
First, those with PD were matched with people in the other groups for age, sex, race and ethnicity, and length of diagnosis to compare the frequency of gut conditions that appeared in the electronic medical records for an average of six years before their diagnosis with PD.
The researchers then tested Braak’s hypothesis in a different way, by dividing all participants diagnosed with any of 18 gut conditions into separate groups. People in these groups were matched with people with a particular gut condition, and their medical records were monitored for five years to see how many developed PD or another neurological disorder.
Both analyses indicated that four gut conditions were associated with an increased risk of a PD diagnosis compared with other neurological conditions. Specifically, gastroparesis (delayed stomach emptying), dysphagia (difficulty swallowing), and constipation were all associated with a more than doubled risk of PD in the five years preceding diagnosis. Irritable bowel syndrome (IBS) without diarrhea was associated with a 17% increase in risk.
While neither inflammatory bowel disease nor vagotomy, the removal of the vagus nerve to treat peptic ulcer, were associated with a heightened risk of PD, they were found to be more prevalent before the onset of Alzheimer’s disease or cerebrovascular disease.
Interestingly, the removal of the appendix was found to be protective against PD, prompting researchers to question its potential role in the disease process underlying the condition.
As this study was observational, it can’t establish a causative relationship between gut conditions and PD. And the researchers are aware that the study had some limitations, namely that the monitoring period was relatively short and the diagnostic information in the medical records may have been incomplete.
Nonetheless, they conclude that the study’s findings are important in terms of diagnosing PD.
“This study is the first to establish substantial observational evidence that the clinical diagnosis of not only constipation, but also dysphagia, gastroparesis and irritable bowel syndrome without diarrhea might specifically predict the development of Parkinson’s disease,” the researchers said.
The study was published in the journal Gut.