Objective:

The primary objective is to analyze and compare the prevalence of RBD in LRRK2-positive individuals across different stages, including healthy controls (HC), prodromal Parkinson’s (PPD), and established PD patients.

Background: Rapid Eye Movement (REM) sleep behavior disorder (RBD) has evolved from being considered idiopathic to a recognized early clinical sign of various neurodegenerative disorders, including Parkinson’s disease (PD). This study focuses on individuals with mutations in the leucine-rich repeat kinase 2 (LRRK2) gene associated with late-onset PD.

Method:

Data from the Parkinson Progression Marker’s Initiative (PPMI) website, downloaded on December 11, 2023, were analyzed. The study included 175 HCs, 276 PPDs, and 516 PD patients, all possessing the LRRK2 mutation. Exclusion criteria were set for subjects under 30 years old. The cohorts were compared using the Chi-square test. Specific questions highlighting differences between PD stages were identified. Additionally, the study investigated the association between RBD and cognitive decline in PD. Prevalence rates of comorbidities such as stroke, restless legs syndrome (RLS), narcolepsy, and depression were examined.

Results:

RBD prevalence was 18%, 30%, and 33.33% in HCs, PPDs, and PD patients, respectively. The study highlighted specific questions differentiating between various stages of Parkinson’s. Only 0.6%, 2.2%, and 2.5% of HC, PPD, and PD subjects reported a history of stroke. Higher rates of RLS, narcolepsy, and depression were observed in PPD and PD cohorts compared to HCs. Notably, “speaking in sleep” emerged as a parameter differentiating between PPD and PD patients. Although a statistically significant difference in RBD prevalence was observed between HCs and PPD and PD cohorts, no distinction was found between PPD and PD.

Conclusion:

This research underscores the importance of identifying RBD as a prodromal marker for PD in LRRK2-positive individuals. While significant differences were noted between healthy controls and both PPD and PD cohorts regarding RBD prevalence, further exploration is needed to discern specific nuances in the progression from prodromal to manifest parkinsonism. Comprehensive assessment of motor and non-motor symptoms, including cognitive decline, becomes crucial for identifying individuals at risk for developing PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rbd-unmasked-lrrk2-and-the-prodromal-path-to-parkinsons-disease/