Journal article
The Prodromal Synucleinopathy Rating Scale: An Assessment in Patients With REM Sleep Behavior Disorder
Neurology, Vol.107(1), e218176
07/14/2026
DOI: 10.1212/WNL.0000000000218176
PMID: 42302227
Abstract
Background and ObjectivesClinical trials in REM sleep behavior disorder (RBD) to delay or prevent the development of Parkinson disease (PD), dementia with Lewy bodies (DLBs), and multiple system atrophy (MSA) will soon begin. The Prodromal Synucleinopathy Rating Scale (PSRS) was developed to capture the breadth and severity of clinical burden of prodromal disease. We analyzed the clinicometric properties and reliability of the PSRS in the North American Prodromal Synucleinopathy (NAPS) cohort.MethodsPSRS ratings were examined for visits conducted from August 2022-June 2025 on participants who did not have overt PD, DLB, or MSA (n = 348). Clinician raters used clinical judgement to evaluate signs and symptoms within each domain. Scores range from 0 (none) to a maximum of 2-4 points per domain, with a total maximum score of 25. The domains include cognitive (COG), behavioral/psychiatric (PSY), motor-axial (MAX), motor-appendicular (MAP), autonomic (AUT), sleep (SLP), and sensory (SEN). Spearman correlations were generated between ratings for each domain, the total sum score (SUM), and with independent measures of similar constructs. Test-retest reliability for 20 case examples protocols among 20 different raters was quantified using Bayesian generalized linear mixed-effects model.ResultsParticipants were 79% male with a mean age of 65.4 ± 10.4 years. The following correlations were statistically significant at p < 0.0001: COG with Montreal Cognitive Assessment (r = −0.42) and Clinical Dementia Rating-Sum of Boxes (r = 0.77); PSY with Neuropsychiatric Inventory-Questionnaire (r = 0.38); MAX and MAP with the Movement Disorders Society-Unified Parkinson Disease Rating Scale Motor (r = 0.65 and 0.75, respectively); AUT with Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (r = 0.39); SLP with Epworth Sleepiness Scale (r = 0.23); and SEN with Brief Smell Identification Test (r = −0.66). The PSRS SUM was correlated with the Functional Assessment Scale (r = 0.47), Schwab and England Activities of Daily Living (r = −0.58), and Clinician Global Impression of Severity (r = 0.29, p < 0.0001 for each). The inter-rater and intrarater reliability means ranged from 0.76 to 0.98.DiscussionIn this large multicenter RBD cohort, moderate to strong correlations were observed between PSRS domains and multiple independent measures of clinical burden. Reliability data were good to excellent. These findings demonstrate preliminary validity for the PSRS for measuring synucleinopathy clinical burden in those with RBD.Trial Registration InformationNCT05826457 NAPS Consortium Website: naps-rbd.org/
Details
- Title: Subtitle
- The Prodromal Synucleinopathy Rating Scale: An Assessment in Patients With REM Sleep Behavior Disorder
- Creators
- Bradley F. Boeve - Mayo Clinic in ArizonaYuzheng Nie - Washington University in St. LouisRuijin Lu - Washington University in St. LouisHernis De La Cruz - Washington University in St. LouisAlon Y. Avidan - UCLA HealthDonald L. Bliwise - Emory UniversityMeghan C. Campbell - Washington University in St. LouisSusan R. Criswell - Barrow Neurological InstituteAlbert A. Davis - Washington University in St. LouisKevin Duff - Oregon Health & Science UniversityJonathan Elliott - Oregon Health & Science UniversityTanis J. Ferman - Mayo Clinic in ArizonaJulie A. Fields - Mayo Clinic in ArizonaLeah K. Forsberg - Mayo Clinic in ArizonaJean-Francois Gagnon - Université du Québec à MontréalMichael Howell - University of MinnesotaDaniel E. Huddleston - Emory UniversityMiranda M. Lim - Oregon Health & Science UniversityJessica Locke - Oregon Health & Science UniversityStuart J. McCarter - Mayo Clinic in ArizonaJennifer McLeland - Washington University in St. LouisMitchell G. Miglis - Stanford UniversityToji Miyagawa - Mayo Clinic in ArizonaLee E. Neilson - Oregon Health & Science UniversityKendall Nichols - Emory UniversityAmélie Pelletier - Montreal Neurological Institute and HospitalCarlos H. Schenck - University of MinnesotaErik K. St Louis - Mayo Clinic in ArizonaOliver Sum-Ping - Palo Alto UniversityLynn Marie Trotti - Emory UniversityAleksandar Videnovic - Massachusetts General HospitalChengjie Xiong - Washington University in St. LouisRonald Postuma - Montreal Neurological Institute and HospitalYo-El S. Ju - Washington University, St. Louis, MONAPS Consortium
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.107(1), e218176
- DOI
- 10.1212/WNL.0000000000218176
- PMID
- 42302227
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Publisher
- Lippincott Williams & Wilkins
- Grant note
- NIH
This work was supported by the NIH under award numbers R34AG056639, U19AG071754, P30AG062677, and P30AG066518. This manuscript is the result of funding in whole or in part by the NIH. It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given a right to make this manuscript publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH.
- Language
- English
- Date published
- 07/14/2026
- Academic Unit
- Neurology
- Record Identifier
- 9985175464402771
Metrics
9 Record Views