Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study

Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD.

We performed a population-based cohort study using Swedish national register data. Adults aged ≥35 years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics.

Amongst the study population (N = 4 670 423), 34 868 (0.75%) had a history of CDI. A total of 165 and 47 035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2 years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups.

Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.