Objective: To determine whether newly diagnosed Parkinson’s disease (PD) patients with REM sleep behavior disorder (RBD) are more likely to have symptoms of autonomic dysfunction.

Background: RBD is highly associated with development of a-synucleinopathies but only 51% of PD patients have RBD^1,2. We addressed whether PD with and without RBD have different clinical phenotypes and progression.

Method: Hypothesis driven analysis of 295 early stage PD patients within 2 years from diagnosis on no PD medications from the Parkinson’s Progressive Marker Initiative (PPMI) cohort were obtained. Genetic, SWEED and prodromal subgroups were excluded from analysis. RBDSQ equal or greater than 1 for item 6 (q6) was used to identify patients with RBD as this cutoff has greater sensitivity and specificity for identifying true RBD in PD^3,4

Results: Subjects from baseline visit were divided in RBD+ (RBDSQ q6>1, n=128) and RBD- (RBDSQ q6<1, n=167). We considered SCOPA subscores (gastrointestinal(GI), urinary(UR), thermoregulation(THERM), cardiovascular(CV), pupillomotor(PM), sex(SEX)), sense of smell (UPSIT), anxiety (STAIT_trait), depression (GDS), motor (updrs_part3) and cognitive function (MOCA), UPDRS total score. Shapiro-Wilk and Mann-Whitney test for non-parametric data were used for the analyses. SCOPA sub-scores for the majority of the autonomic symptoms (GI, THERM, CV, PM) but not UR and SEX, were significantly higher in the REM+ cohort (p=<0.005). The other traits did not show statistically significant differences. Statistical significance between the two groups for GI, THERM, CV remained consistent using other thresholds for differentiating REM+ vs REM- groups (RBDSQ total score greater than 5 or combined RBDSQ total score and q6).

Conclusion: Our hypothesis driven analyses show that early stage PD patients with RBD have greater prevalence of autonomic symptoms, without worse UPDRS motor scores. This suggests that brainstem and peripheral autonomic symptoms cluster together, but are not associated with more diffuse involvement of motor systems and cognitive impairment at this early stage of PD. Prior analyses of PPMI data have identified a “diffuse/malignant” subtype associated with higher UPDRS motor score, RBDSQ score, autonomic symptoms (SCOPA-AUT) and worse cognitive impairment^5.6. These differences might be accounted by our more stringent criteria for RBD or our statistical approach using specific hypothesis versus cluster driven analyses.

References: 1. Hogl, B., A. Stefani, and A. Videnovic, Idiopathic REM sleep behaviour disorder and neurodegeneration – an update. Nat Rev Neurol, 2018. 14(1): p. 40-55. 2. Mollenhauer, B., et al., Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology, 2013. 81(14): p. 1226-34. 3. Halsband, C., et al., The REM Sleep Behavior Disorder Screening Questionnaire is not Valid in De Novo Parkinson’s Disease. Mov Disord Clin Pract, 2018. 5(2): p. 171-176. 4. Stiasny-Kolster, K., et al., The REM sleep behavior disorder screening questionnaire–a new diagnostic instrument. Mov Disord, 2007. 22(16): p. 2386-93. 5. Fereshtehnejad, S.M., et al., Clinical criteria for subtyping Parkinson’s disease: biomarkers and longitudinal progression. Brain, 2017. 140(7): p. 1959-1976. 6. Erro, R., et al., Clinical clusters and dopaminergic dysfunction in de-novo Parkinson disease. Parkinsonism Relat Disord, 2016. 28: p. 137-40.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rbd-and-autonomic-dysfunction-in-newly-diagnosed-parkinsons-disease-patients/