Body-first subtype of Parkinson's disease with REM-sleep behaviour disorder is associated with non-motor dominant phenotype


Pavelka L, Rauschenberger A, Landoulsi Z, Pachchek S, Marques T, Gomes CPC, Glaab E, May P, Krüger R on behalf of the NCER-PD Consortium

Study Objectives: 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 analysed the presence of probable REM-Sleep behaviour disorder (pRBD) and the APOE ε4 carrier status as potential sub-group stratifiers.

Methods: A total of 400 iPD patients were included in the cross-sectional analysis from the baseline visit with a completed REM-Sleep Behaviour Disorder 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 motor and non-motor symptoms adjusted for disease duration and age, (ii) the effects of sex on pRBD and other clinical outcomes and (iii) the association of APOE ε4 and pRBD.

Results: iPD-pRBD was significantly associated with autonomic dysfunction burden (SCOPA-AUT), level of depressive symptoms (BDI-I), scores in MDS-UPDRS I, frequency of hallucinations and constipation. Moreover, iPD-pRBD was significantly negatively associated with quality of life (PDQ-39) and sleep (PDSS). No significant association between sex and pRBD or APOE ε4 and pRBD in iPD was found.

Conclusion: We identified a characteristic phenotype of iPD-pRBD with more severe non-motor symptoms compared to iPD non-pRBD. We did not observe an significant association between APOE ε4 and pRBD, which further supports the body-first hypothesis. The results suggest an RBD-specific PD endophenotype, characterised by predominant autonomic dysfunction, hallucinations and depression, corroborating the concept of a distinctive body-first subtype of PD.

Data


The dataset for this manuscript is not publicly available as it is linked to the Luxembourg Parkinson’s Study and its internal regulations. Any requests for accessing the dataset can be directed to request.ncer-pd@uni.lu.

source code


The source code is available here.