Body-first subtype of Parkinson’s disease with probable 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
Background: The hypothesis of body-first vs brain-first subtype of PD has been proposed with REM-Sleep behaviour 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 analysed the presence of probable RBD, sex, 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 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 effects of sex on pRBD and (iii) the association of APOE ε4 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 ε4 and pRBD in iPD was found nor did we determine a significant effect of APOE ε4 on the PD phenotype.
Conclusion: We identified an RBD-specific PD endophenotype, characterised 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 ε4 and pRBD suggesting both factors having an independent effect on cognitive decline in iPD.