Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy

Daniel Weintraub; Michele K. York; Roseanne Dobkin; Anuprita R. Nair; Ryan Kurth; David Erick Lafontant; Chelsea Caspell-Garcia; Roy N. Alcalay; Ethan G. Brown; Lana M. Chahine; Christopher Coffey; Tatiana Foroud; Douglas Galasko; Karl Kieburtz; Kenneth Marek; Kalpana Merchant; Brit Mollenhauer; Kathleen L. Poston; Andrew Siderowf; Cristina Simonet; Tanya Simuni; Caroline M. Tanner; Thomas F. Tropea; Aleksandar Videnovic; Parkinson's Progression Markers Initiative

doi:10.1002/acn3.70399

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Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy

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Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy

Daniel Weintraub, Michele K. York, Roseanne Dobkin, Anuprita R. Nair, Ryan Kurth, David Erick Lafontant, Chelsea Caspell-Garcia, Roy N. Alcalay, Ethan G. Brown, Lana M. Chahine, …

Annals of clinical and translational neurology

04/21/2026

DOI: 10.1002/acn3.70399

PMID: 42015618

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Abstract

Objective Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal state for Lewy body disorders and exhibits biological heterogeneity that may influence clinical expression and progression. We examined clinical features in individuals with iRBD and biomarker-defined synucleinopathy. Methods Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, multi-center observational study. Participants included polysomnogram (PSG)-confirmed iRBD individuals who were cerebrospinal fluid (CSF) α-synuclein seed amplification assay positive with no clinical diagnosis of Parkinson's disease or dementia with Lewy bodies, along with robust healthy controls (HCs). Clinical and biological features of prodromal PD and DLB, including mild cognitive impairment (MCI), subthreshold parkinsonism, and a range of neuropsychiatric, autonomic, and sensory symptoms, were assessed. Results Compared with HCs (N = 136), iRBD participants (N = 197) demonstrated worse cognitive performance, including a lower cognitive summary score (p < 0.0003, effect size = 0.41), and higher odds of subthreshold parkinsonism (OR = 24.5), and neuropsychiatric (OR = 3.5), autonomic (OR = 7.2) and sensory symptoms (OR = 13.2). Common features included hyposmia (75%), pain (54%), urinary problems (52%), constipation (49%), lightheadedness (40%) and anxiety (36%), whereas rates of MCI (32%), subthreshold parkinsonism (27%) and psychosis (7%) were lower. iRBD participants with abnormal dopamine transporter imaging had higher anxiety scores and antidepressant use. Although only 10% met criteria for prodromal DLB due to the requirement for MCI, most exhibited multi-domain impairment. Interpretation iRBD with synucleinopathy is associated with multi-domain clinical impairment before clinical neurodegenerative disease diagnosis, supporting broad clinical assessment in early biomarker-defined synuclein disease.

Dementia

autonomic

mild cognitive impairment

neuropsychiatric

RBD

Details

Title: Subtitle: Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy
Creators: Daniel Weintraub - University of Pennsylvania
Michele K. York - Baylor College of Medicine
Roseanne Dobkin - Rutgers, The State University of New Jersey
Anuprita R. Nair - University of Iowa
Ryan Kurth - University of Iowa
David Erick Lafontant - University of Iowa
Chelsea Caspell-Garcia - University of Iowa
Roy N. Alcalay - Tel Aviv Sourasky Medical Center
Ethan G. Brown - University of California, San Francisco
Lana M. Chahine - University of Pittsburgh
Christopher Coffey - University of Iowa
Tatiana Foroud - Indiana University Indianapolis
Douglas Galasko - University of California San Diego
Karl Kieburtz - University of Rochester
Kenneth Marek - Institute for Neurodegenerative Disorders
Kalpana Merchant - Northwestern University
Brit Mollenhauer - Universitätsmedizin Göttingen
Kathleen L. Poston - Stanford University
Andrew Siderowf - University of Pennsylvania
Cristina Simonet - Queen Mary University of London
Tanya Simuni - Northwestern University
Caroline M. Tanner - University of California, San Francisco
Thomas F. Tropea - Institute for Neurodegenerative Disorders
Aleksandar Videnovic - Massachusetts General Hospital
Parkinson's Progression Markers Initiative
Resource Type: Journal article
Publication Details: Annals of clinical and translational neurology
DOI: 10.1002/acn3.70399
PMID: 42015618
NLM abbreviation: Ann Clin Transl Neurol
ISSN: 2328-9503
eISSN: 2328-9503
Publisher: Wiley
Grant note: Michael J. Fox Foundation for Parkinson's Research: Parkinson's Progression Markers Initiative
This work was supported by the Michael J. Fox Foundation for Parkinson's Research, Parkinson's Progression Markers Initiative.
Language: English
Electronic publication date: 04/21/2026
Academic Unit: Biostatistics
Record Identifier: 9985157515902771

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