Objective: To examine whether individuals with a history of Clostridium difficile (C. diff) infection have an elevated risk of developing Parkinson’s disease (PD).

Background: The gastrointestinal system has been postulated to mediate the pathophysiology of PD. C. diff infection (CDI) is a leading cause of infectious diarrhea and disproportionally affects older people. Nonetheless, whether CDI is associated with PD risk is unknown.

Method: Adult participants (age >= 35) in the Swedish Population and Housing Census 1990 (FoB90) were followed up from 1997 to 2013 for diagnosis of CDI and incident PD, using the Swedish National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing CDI-exposed and non-exposed individuals were estimated with Cox proportional hazards model, adjusting for attained age, time since infection, gender, birth country, education attainment and comorbidities. Stratified analyses were performed to assess whether the association differed by the source of infection diagnosis (inpatient vs outpatient), presence of recurrent infection(s), and history of pre-infection use of antibiotics.

Results: The study cohort consisted of N=4,873,154 Swedish residents, of whom 0.75% were exposed to C. diff. In total, 165 and 47,035 incident PD cases were identified amongst the CDI and non-CDI groups during a mean follow-up of 5.36 person-years (PYs) and 15.29 PYs, respectively. In the adjusted Cox model, PD risk was higher among exposed than non-exposed individuals within the first two years since exposure to CDI [HR (95% CI): 1.31 (1.08, 1.59)]. This association attenuated over time and became inverse 8-10 years after infection. The short-term increased PD risk was observed in all CDI subgroups; whereas the long-term inverse relationship between CDI and PD risk was only observed among individuals who were hospitalized at CDI diagnosis, those who had no recurrent infections, and those who did not use antibiotics within 6 months prior to a CDI.

Conclusion: Our findings imply a positive association between CDI and PD risk at early stages after infection, which may be due to the surveillance bias. In long-term follow-up, individuals exposed to CDI may be at lower risk of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clostridium-difficile-infection-and-risk-of-parkinsons-disease-a-swedish-population-based-cohort-study/