Objective: Parkinson's disease (PD) may be caused by an enteric neurotropic pathogen entering the brain through the vagal nerve, a process that may take over 20 years. We investigated the risk of PD in patients who underwent vagotomy and hypothesized that truncal vagotomy is associated with a protective effect, whereas superselective vagotomy has a minor effect.

Methods: We constructed cohorts of all patients in Denmark who underwent vagotomy during 1977-1995 and a matched general population cohort by linking Danish registries. We used Cox regression to compute hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders.

Results: Risk of PD was decreased in patients who underwent truncal (HR = 0.85; 95% CI = 0.56-1.27; follow-up of >20 years: HR = 0.58; 95% CI: 0.28-1.20) compared to superselective vagotomy. Risk of PD was also decreased after truncal vagotomy when compared to the general population cohort (overall adjusted HR = 0.85; 95% CI: 0.63-1.14; follow-up >20 years, adjusted HR = 0.53; 95% CI: 0.28-0.99). In patients who underwent superselective vagotomy, risk of PD was similar to the general population (HR = 1.09; 95% CI: 0.84-1.43; follow-up of >20 years: HR = 1.16; 95% CI: 0.80-1.70). Statistical precision of risk estimates was limited. Results were consistent after external adjustment for unmeasured confounding by smoking.

Interpretation: Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD.

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