Body-First Subtype of Parkinson’s Disease with Probable REM-Sleep Behavior Disorder Is Associated with Non-Motor Dominant Phenotype

Abstract

Background: The hypothesis of body-first vs. brain-first subtype of PD has been proposed with REM-Sleep behavior disorder (RBD) defining the former. The body-first PD presumes an involvement of the brainstem in the pathogenic process with higher burden of autonomic dysfunction. Objective: To identify distinctive clinical subtypes of idiopathic Parkinson’s disease (iPD) in line with the formerly proposed concept of body-first vs. brain-first subtypes in PD, we analyzed the presence of probable RBD, sex, and the APOE ɛ4 carrier status as potential sub-group stratifiers. Methods: A total of 400 iPD patients were included in the cross-sectional analysis from the baseline dataset with a completed RBD Screening Questionnaire (RBDSQ) for classifying as pRBD by using the cut-off RBDSQ≥6. Multiple regression models were applied to explore (i) the effects of pRBD on clinical outcomes adjusted for disease duration and age, (ii) the effect of sex on pRBD, and (iii) the association of APOE ɛ4 and pRBD. Results: iPD-pRBD was significantly associated with autonomic dysfunction (SCOPA-AUT), level of depressive symptoms (BDI-I), MDS-UPDRS I, hallucinations, and constipation, whereas significantly negatively associated with quality of life (PDQ-39) and sleep (PDSS). No significant association between sex and pRBD or APOE ɛ4 and pRBD in iPD was found nor did we determine a significant effect of APOE ɛ4 on the PD phenotype. Conclusion: We identified an RBD-specific PD endophenotype, characterized by predominant autonomic dysfunction, hallucinations, and depression, corroborating the concept of a distinctive body-first subtype of PD. We did not observe a significant association between APOE ɛ4 and pRBD suggesting both factors having an independent effect on cognitive decline in iPD.

Disease progression in proposed brain-first and body-first Parkinson’s disease subtypes

“…Additionally, we also found PD pRBD+ group exhibited higher NMSS score at baseline. This aligns with the notion that body-first patients should theoretically show damage to the autonomic nervous system and the lower brainstem structures earlier in the disease course compared to brain-first patients 4 and is supported by the previous finding that body-first subtype is associated with non-motor dominant phenotype 14 . Therefore, our study adds to the prior body of evidence that the body-first subtype shows more severe non-motor impairments than the brain-first subtype.…”

Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson’s Disease Defined by REM-Sleep Behavior Disorder and Hyposmia

“…Furthermore, given that our P-PD cohort is defined by pRBD and hyposmia, we need to highlight that our observations focus mainly on one specific subtype of P-PD, as we do not control for all potential prodromal markers and that it cannot be generalized on all the P-PD subtypes. Especially because iRBD in PD has been associated with higher burden of non-motor symptoms, such as impaired cognitive functions [36,39]. In order to address the heterogeneity in P-PD, we are currently working on the investigation of a population based on additional prodromal signs, e.g.…”

Luxembourg Parkinson’s study -comprehensive baseline analysis of Parkinson’s disease and atypical parkinsonism

“…Age at disease onset (AAO) was defined as age at diagnosis of the neurodegenerative disorder. Probable Rapid Eye Movement (REM)-Sleep Behaviour Disorder (pRBD) was defined based on the RBD Screening Questionnaire total score (RBDSQ) ≥ 6 for patient groups and RBDSQ ≥ 5 for controls ( 28 ). The information on environmental exposure and medication use was based on the modified PD Risk Factor Questionnaire (PD-RFQ-U) Epi Info™ developed by Caroline Tanner ( 17 ).…”