Objective: To elucidate the role of Parkinson’s disease (PD)-related brain metabolic patterns as a biomarker in isolated rapid-eye-movement sleep behavior disorder (iRBD) for clinical correlation and future disease conversion.

Background: Disease-related metabolic patterns derived from Parkinson’s disease (PD-RP) and de-novo PD with probable RBD (dnPDRBD-RP) have been proposed as a biomarker in iRBD. However, the direct comparisons between the metabolic patterns derived from the long-standing and de novo PD patients (PD-RP vs. dnPDRBD-RP) in terms of clinical biomarker correlation and predictability of future phenoconversion have not been investigated.

Method: We prospectively enrolled 30 iRBD patients, 25 de novo PD patients with a premorbid history of RBD, 21 long-standing PD patients on stable treatment and 24 healthy controls. Participants underwent ¹⁸F-Fluorodeoxyglucose (FDG) PET scans and clinical tests for olfaction and cognition, and the Movement disorders society-Unified PD Rating Scale (MDS-UPDRS) evaluation. From FDG-PET scans, we derived two metabolic patterns from the long-standing PD group (PD-RP) and PD de novo group (dnPDRBD-RP). Subsequently, we calculated the PD-RP and dnPDRBD-RP expression scores in iRBD patients. We validated the two metabolic patterns in each PD group and our separate iRBD cohort (n=14).

Results: The two patterns significantly correlated with each other and were spatially overlapping yet distinct. The MDS-UPDRS motor scores significantly correlated with PD-RP (p = 0.013) but insignificant with dnPDRBD-RP scores (p = 0.076). In contrast, dnPDRBD-RP correlated with olfaction in butanol threshold test (p = 0.018) in iRBD subjects, but PD-RP did not (p = 0.21). High dnPDRBD-RP expression in iRBD patients predicted future phenoconversion with all cut-off ranges from 1.5 to 3 standard deviations of the control value, whereas predictability of PD-RP was only significant in a partial range of cut-off.

Conclusion: The present study is the first comparative analysis on two PD-related metabolic patterns of dnPDRBD-RP and PD-RP in a prospective iRBD cohort. dnPDRBD-RP shares the metabolic pattern of PD-RP, yet distinct. Overall, dnPDRBD-RP better reflects prodromal clinical features of PD and better predicts future phenoconversion in iRBD as it was derived from de-novo PD with a history of preceding RBD which may incorporate the compensatory change of the prodromal stage of PD.

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