Baseline characteristics of the North American prodromal Synucleinopathy cohort.

Alon Y Avidan, Yo-El S Ju, Bradley F Boeve, Joyce K Lee-Iannotti, David R Shprecher, Mitchell G Miglis, Emmanuel H During, Aleksandar Videnovic, Susan R Criswell, Jennifer McLeland, Carlos H Schenck, Michael J Howell, Jonathan E Elliott, Donald L Bliwise, Daniel E Huddleston, Julie A Fields, Leah K Forsberg, Erik K St Louis, Jean-François Gagnon, Amelie Pelletier, Ronald B Postuma, Allison T Keil, Miranda M Lim

Journal: Annals of clinical and translational neurology 2023;10(4):520-535

PMID: 36751940

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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.

Address: VA Portland Health Care System, Research Service, Portland, Oregon, USA.; Oregon Health & Science University, Neurology, Portland, Oregon, USA.; Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.; Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA.; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, USA.; Neurology, VA Portland Health Care System, Portland, Oregon, USA.; Mental Illness Research Education and Clinical Center, VA Portland Health Care System, Portland, Oregon, USA.; National Center for Rehabilitative Auditory Research, VA Portland Health Care System, Portland, Oregon, USA.; Montreal Neurological Institute, McGill University, Montreal, Québec, Canada.; Psychology, Université du Québec à Montréal, Montreal, Québec, Canada.; Hôpital du Sacré-Coeur de Montréal, Center for Advanced Research in Sleep Medicine, Montreal, Québec, Canada.; Mayo Clinic, Neurology and Medicine, Rochester, Minnesota, USA.; Neurology, Emory University, Atlanta, Georgia, USA.; Neurology, Sleep Disorders Center, University of California Los Angeles, Los Angeles, California, USA.; Neurology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA.; Hennepin County Medical Center, Minnesota Regional Sleep Disorders Center, Minneapolis, Minnesota, USA.; Washington University School of Medicine, St. Louis, Missouri, USA.; Movement Disorders Unit, Division of Sleep Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Neurological Clinical Research Institute, Boston, Massachusetts, USA.; Psychiatry and Behavioral Sciences, Stanford University, Redwood City, California, USA.; Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.; Neurology, Banner Sun Health Research Institute, Phoenix, Arizona, USA.

DOI: 10.1002/acn3.51738

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MeSH Terms: Female, Humans, Male, Lewy Body Disease, Longitudinal Studies, Multiple System Atrophy, Parkinson Disease, REM Sleep Behavior Disorder, Synucleinopathies