Background: Isolated REM sleep behavior disorder (iRBD) is the most specific prodromal marker of Parkinson′s disease (PD), often accompanied by various non-motor symptoms. In PD, non-motor symptoms are strongly associated with reduced health-related quality of life (hrQoL). Objectives: To identify factors linked to poorer hrQoL in patients with iRBD and to compare their hrQoL to healthy control participants (HC) and patients with PD. Methods: Sixty-two patients with iRBD (M = 66.44±6.14), 29 patients with PD (M = 67.21±7.23), and 19 HC (M = 67.57±8.16) were included. We administered the 36-Item Short Form Health Survey (SF-36) to assess hrQoL. Additionally, participants underwent a comprehensive clinical evaluation of non-motor symptoms. Results: The SF-36 total score was significantly lower in patients with iRBD (83.33±16.96) compared to HC (92.29±5.49, U = 390.00, Z = -2.218, p = .027, r = 0.246). Poorer hrQoL in patients with iRBD was linked to self-reported neuropsychiatric symptoms, sleep-wake disturbances, and a higher burden of autonomic symptoms (all r = -.25 to -.76, all p < .05). Multiple regression analysis revealed fatigue and depressive symptoms as significant predictors of poorer hrQoL in patients with iRBD (F (5.56) = 51.59, p < .001, adjusted R2 = 0.81). Conclusions: This study highlights the importance of non-motor symptoms for hrQoL in prodromal PD, irrespective of motor symptoms. Fatigue and depressive symptoms arise as the most relevant therapeutic targets in the prodromal stage of PD to optimize the patient′s quality of life.

S.R., M.-S.L., A.S., J.K., and K.-L.W. report no disclosures. C.E.J.D. is supported by the Clinician Scientist Program (CCSP), funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, FI 773/15-1). G.R.F. receives royalties from the publication of the books Funktionelle MRT in Psychiatrie und Neurologie, Neurologische Differentialdiagnose, and SOP Neurologie and received honoraria for speaking engagements from Forum fuer medizinische Fortbildung FomF GmbH as well as grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project-ID 431549029, SFB 1451. A.O. received a grant from the Koeln Fortune Program (grant-no. 329/2021), Faculty of Medicine, University of Cologne, and the ″Novartis-Stiftung fuer therapeutische Forschung″, both outside the submitted work. M.S. received grants from the Else Kroener-Fresenius-Stiftung (grant number 2019_EKES.02), and the Koeln Fortune Program, Faculty of Medicine, University of Cologne. M.S. receives additional funding from the program ″Netzwerke 2021″, an initiative of the Ministry of Culture and Science of the State of Northrhine Westphalia. The sole responsibility for the content of this publication lies with the authors.

S.R., M.-S.L., A.S., J.K. and K.-L.W. report no disclosures. C.E.J.D. received grants from the Clinician Scientist Program (CCSP), funded by the German Research Foundation (DFG, FI 773/15-1). G.R.F. receives royalties from the publication of the books Funktionelle MRT in Psychiatrie und Neurologie, Neurologische Differentialdiagnose, and SOP Neurologie and received honoraria for speaking engagements from Forum fuer medizinische Fortbildung FomF GmbH as well as grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project-ID 431549029, SFB 1451. A.O. received a grant from the Koeln Fortune Program (grant-no. 329/2021), Faculty of Medicine, University of Cologne, and the ″Novartis-Stiftung fuer therapeutische Forschung″, both outside the submitted work. M.S. received grants from the Else Kroener-Fresenius-Stiftung (grant number 2019_EKES.02), and the Koeln Fortune Program, Faculty of Medicine, University of Cologne. M.S. receives funding from the program ″Netzwerke 2021″, an initiative of the Ministry of Culture and Science of the State of Northrhine Westphalia. The sole responsibility for the content of this publication lies with the authors.

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