Constipation is linked to accelerated cognitive and motor decline in isolated REM sleep behavior disorder

Introduction: Constipation is associated with higher clinical severity and predicts cognitive decline in Parkinson's disease (PD). Whether the non-motor marker is associated with unfavorable motor and cognitive trajectories from the prodromal stage remains unclear. Methods: In a longitudinal prospective cohort of subjects with isolated REM sleep behavior disorders (iRBD), subjects underwent repeated MDS-UPDRS and Mini-Mental Status Examination (MMSE) assessments. Generalized-estimating-equations (GEE) regression model was used to compare the time-dependent trajectories of MDS-UPDRS-III and MMSE scores between subjects with and without constipation at baseline. Results: Twenty-nine subjects with constipation at baseline (iRBD+constipation) and 24 without (iRBD-constipation) were followed over 4.085 +/- 2.645 years. The iRBD+constipation group presented faster decline of both MDS-UPDRS-III and MMSE scores, with additional estimated annual progression of +1.242 and -0.713 points, respectively, compared to the iRBD-constipation group (time*group p < 0.05). Conclusion: Constipation in isolated RBD is associated with accelerated progression of cognitive impairment and motor symptoms.