Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker‐Defined Synucleinopathy
Year: 2026
Type: article
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.
DOI: 10.1002/acn3.70399
Authors: 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, The Parkinson's Progression Markers Initiative
Institutions: University of Pennsylvania, Baylor College of Medicine, Rutgers, The State University of New Jersey, University of Iowa, Columbia University Irving Medical Center, Tel Aviv Sourasky Medical Center, University of California, San Francisco, University of Pittsburgh, Indiana University Indianapolis, Indiana University School of Medicine, University of California San Diego, University of Rochester Medicine, University of Rochester, Institute for Neurodegenerative Disorders, Northwestern University, Universitätsmedizin Göttingen, Stanford Medicine, Stanford University, Queen Mary University of London, Massachusetts General Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: Michael J. Fox Foundation for Parkinson's Research, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Sanofi, Biogen, Teva Pharmaceutical Industries, Celgene, Jazz Pharmaceuticals, Neurocrine Biosciences, Verily Life Sciences, Voyager Therapeutics, Servier, H. Lundbeck A/S, Sun Pharma, Genentech, Allergan, Avid Radiopharmaceuticals
OpenAlex ID: W7155155122