Objective: To assess whether the co-occurrence of neurogenic orthostatic hypotension (nOH) and REM sleep behavior disorder (RBD) is associated with a more severe clinical presentation of motor symptoms (MS) and non-motor symptoms (NMS) in early-stage Parkinson’s disease (PD).

Background: nOH and RBD commonly co-occur and are independently associated with more severe MS and NMS, including accelerated PD progression.^1-4 Their combined impact on PD is unknown.

Method: We used non-parametric analyses to compare baseline MS and NMS in the Parkinson’s Progression Marker Initiative cohort based on the presence or absence of nOH and RBD (PD, PD+nOH, PD+RBD, and PD+Both). We defined nOH as a ratio ≤ 0.5 for 𝚫 systolic blood pressure /𝚫 HR, supine to standing after 3 minutes, and RBD as RBD Screening Questionnaire (RBDSQ) >4 and “yes” to the most specific question, 6.3. MS scales included Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) II and III. NMS scales included MDS-UPDRS I, Geriatric Depression Scale (GDS), State-Trait Anxiety Inventory (STAI), and Montreal Cognitive Assessment (MOCA).

Results: No between-group differences were seen in the time since diagnosis or symptom onset [Table 1]. The PD group was significantly younger than the PD+nOH and PD+Both groups [Table 1]. The PD+Both group had a significantly higher proportion of males than the PD and PD+nOH groups [Table 1]. The PD+Both group did not differ from the PD+nOH group on nOH ratio values nor from the PD+RBD group on RBDSQ score [Table 1]. Neither MS nor NMS statistically differed between PD, PD+nOH, or PD+RBD groups. The PD+Both group had significantly higher MS scores than the PD group on MDS-UPDRS II and MDS-UPDRS III [Figure 1]. The PD+Both group had significantly higher NMS scores than the PD group on MDS-UPDRS I, GDS, STAI, and MOCA visuospatial/executive function [Figure 2, Table 2].

Conclusion: nOH and RBD are associated with a more severe clinical presentation when they present concurrently, but not independently, in early-stage PD. This increased severity may be independent of nOH and RBD, as there were no differences in MS or NMS when only one of these conditions was comorbid with PD. These data suggest that the co-occurrence of nOH and RBD may identify a clinically distinct subgroup within PD. This has important implications for early intervention studies and treatment development but should first be verified longitudinally and against known PD biomarkers.

Figure 1

Figure 2

Table 1

Table 2

References: 1. Elliott JE, Bryant-Ekstrand MD, Keil AT, et al. Frequency of orthostatic hypotension in isolated REM sleep behavior disorder: the North American prodromal synucleinopathy cohort. Neurology. Lippincott Williams & Wilkins Hagerstown, MD; 2023;101:e2545–e2559.
2. Folle AD, Paul KC, Bronstein JM, Keener AM, Ritz B. Clinical progression in Parkinson’s disease with features of REM sleep behavior disorder: a population-based longitudinal study. Parkinsonism Relat Disord. Elsevier; 2019;62:105–111.
3. Li L, Guo P, Ding D, et al. Parkinson’s disease with orthostatic hypotension: analyses of clinical characteristics and influencing factors. Neurol Res. Taylor & Francis; 2019;41:734–741
4. Goldstein DS, Holmes C, Sharabi Y, Wu T. Survival in synucleinopathies: A prospective cohort study. Neurology. 2015;85(18):1554-1561. doi:10.1212/WNL.0000000000002086

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-non-motor-symptoms-in-noh-rbd/