Clinical progression in Parkinson's disease with features of REM sleep behavior disorder: A population-based longitudinal study

Abstract

Introduction: Rapid Eye Movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and is associated with incidence of neurodegenerative disorders, especially Parkinson's disease (PD). Whether PD with RBD constitutes a distinct subtype with unique progression is unknown. Here, we investigated motor and cognitive symptom progression in patients with self-reported RBD features in adult life.

Methods: We screened for RBD in a cohort of 776 PD patients whom we ascertained using a population-based strategy. Among participants with at least one follow-up (60%), we compared those with and without probable RBD (pRBD) estimating hazard rate ratios for progression events UPDRS-III≥ 35 and MMSE≤ 24.

Results: Prevalence of pRBD at baseline was 21%. In adjusted Cox regression models among patients with a Postural Instability and Gait Dysfunction (PIGD) phenotype, those with pRBD progressed faster to a UPDRS-III≥ 35 (HR = 1.92, 95% CI = 1.12; 3.27). Also, all patients with pRBD progressed twice as fast to a MMSE score≤ 24 (HR = 2.04, 95% CI = 1.13; 3.69). In sensitivity analyses, using alternative definition of pRBD and accounting for bias due to loss to follow-up results remained similar.

Discussion: Employing data from one of the largest population-based studies of PD, in which movement disorder specialists assessed patients, we confirm evidence that pRBD features are a clinical marker for faster cognitive decline and possibly also motor progression in PD patients, the latter for patients with a PIGD subtype early in disease.

Keywords: Cognitive decline; Motor progression; Parkinson's disease; REM sleep behavior disorder; Sleep.

Figure 1.

Flowchart of Parkinson’s Environment and Genes (PEG) Study, first and second cohorts: baseline and follow-ups

Figure 2.

Hazard rate ratios (HR) estimated for PD clinical progression events and pRBD. ¹Total corresponds to those without the events (UPDRS-III ≥ 35 and MMSE ≤ 24) at baseline. ²Percentages refer to the total participants in each group (with and without pRBD). ³Adjusted for age at diagnosis, sex, PD duration at baseline, race (minority yes/no), pack-years of smoking, baseline cohort, and years of education for MMSE.