Baseline characteristics of the North American prodromal Synucleinopathy cohort

• Type of Material: Article
• Authors: Jonathan E Elliott, VA Portland Health Care System, Research Service; Miranda M Lim, Oregon Health & Science University; Allison T Keil, VA Portland Health Care System, Research Service; Ronald B Postuma, McGill University; Amelie Pelletier, Hop Sacre Coeur Montreal; Jean-François Gagnon, Université du Québec à Montréa; Erik K St Louis, Mayo Clinic; Leah K Forsberg, Mayo Clinic; Julie A Fields, Mayo Clinic; Daniel Huddleston, Emory University; Donald Bliwise, Emory University; Alon Y Avidan, University of California Los Angeles; Michael J Howell, University of Minnesota, Minneapolis; Carlos H Schenck, University of Minnesota, Minneapolis; Jennifer McLeland, Washington University; Susan R Criswell, Washington University; Aleksandar Videnovic, Massachusetts General Hospital; Emmanuel H During, Stanford University; Mitchell G Miglis, Stanford University; David R Shprecher, Banner Sun Health Research Institute; Joyce K Lee-Iannotti, Banner Sun Health Research Institute; Bradley F Boeve, Mayo Clinic; Yo-El S Ju, Washington University
• Language: English
• Date: 2023-02-08
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/acn3.51738
• Title of Journal or Parent Work: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
• Volume: 10
• Issue: 4
• Start Page: 520
• End Page: 535
• Grant/Funding Information: This work was funded by NIH/NIA grants P30 AG62677;, P50 AG016574;, R34 AG056639;, and U19 AG071754; U.S. Department of Veterans Affairs grant 1K2 RX002947.
• Keywords: CONSENSUS STATEMENT; DEMENTIA; Science & Technology; Neurosciences & Neurology; REM-SLEEP; MONTREAL COGNITIVE ASSESSMENT; SLEEP BEHAVIOR DISORDER; Clinical Neurology; Life Sciences & Biomedicine; RISK; Neurosciences; FOLLOW-UP; NEURODEGENERATION; RELIABILITY; PARKINSONS-DISEASE
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment. Methods: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function. Results: Outcomes are primarily reported based on sex (361 total: n = 295 male, n = 66 female), and secondarily based on history of antidepressant use (n = 200 with, n = 154 without; with correction for sex differences) and based on extent of synucleinopathy burden (n = 56 defined as isolated RBD, n = 305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ-9; 39.3% and 31%, respectively). Interpretation: These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials.