Patients with inflammatory bowel disease were about 22% more likely to develop Parkinson’s disease than were unaffected peers in a population-based cohort study spanning more than 3 decades.
The finding “strengthens the theory of a ‘gut-brain axis,’ in which the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede Parkinson’s disease,” wrote Marie Villumsen, PhD, of Bispebjerg and Frederiksberg Hospital in Copenhagen, with her associates.
Thus, clinicians should be vigilant for parkinsonism in patients with inflammatory bowel disease (IBD), the researchers wrote on May 21 in Gut. “Although the absolute risk of Parkinson’s disease [among patients with IBD] remains low, our study points to overlapping pathogenic mechanisms which merit further investigation, as they may represent targets for future therapeutic interventions.”
Gastrointestinal dysfunction can be one of the earliest manifestations of Parkinson’s disease, the researchers noted. Both neurodegenerative disorders and IBD involve chronic inflammation, and both Crohn’s disease and Parkinson’s disease have been linked to aberrations of the LRRK2 gene, which helps regulate inflammation and clearance of alpha-sinuclein, a key component of neuronal Lewy bodies in Parkinson’s disease.
To assess whether IBD directly increases the risk of Parkinson’s disease, the investigators studied individuals from the Danish National Patient Register, which covers all hospitalizations and outpatient visits in Denmark. They matched 76,477 patients with IBD with 7.5 million unaffected individuals of the same sex and age during 1977-2014. Patients with IBD had significantly more comorbidities (P less than .001) than individuals without IBD, so the researchers also controlled for Charlson Comorbidity Index.
In the adjusted analyses, IBD significantly increased the risk of developing Parkinson’s disease among both men (hazard ratio, 1.2) and women (HR, 1.23), irrespective of follow-up time and regardless of whether patients were less than 40 years old (HR, 1.22), 40-65 years old (HR, 1.25), or older than 65 years (HR, 1.30). The association between IBD and Parkinson’s disease also held up after accounting for the possibility that early gut symptoms of Parkinson’s disease were sometimes misdiagnosed as IBD, the researchers wrote.
Interestingly, stratifying by IBD subtype showed that the statistically significant risk factor was ulcerative colitis (HR, 1.35; 95% confidence interval, 1.20-1.52), not Crohn’s disease (HR, 1.12; 95% CI, 0.89-1.40). Prior studies have found that cigarette smoking reduces the risk of both Parkinson’s disease and ulcerative colitis, the investigators noted. They called for additional studies of intestinal inflammation in Parkinson’s disease and the role of the brain-gut axis in the etiology of parkinsonism.
Parkinsonforeningen, Landsforeningen Multipel System Atrofi, and Aage og Johanne Louis-Hansens Fond provided support. The investigators declared no competing interests.
SOURCE: Villumsen M et al. Gut. 2018 May 21. doi: 10.1136/gutjnl-2017-315666.