Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium
Authors: Elliott Jonathan E , Ligman Brittany R , Bryant-Ekstrand Mohini D , Keil Allison T , Powers Katherine , Olivo Cosette , Neilson Lee E , Postuma Ronald B , Pelletier Amélie , Gagnon Jean-François , Gan-Or Ziv , Yu Eric , Liu Lang , St. Louis Erik K , Forsberg Leah K , Fields Julie A , Ross Owen A , Huddleston Daniel E , Bliwise Donald L , Avidan Alon Y , Howell Michael J , Schenck Carlos H , McLeland Jennifer , Criswell Susan R , Videnovic Aleksandar , During Emmanuel H , Miglis Mitchell G , Shprecher David R , Lee-Iannotti Joyce K , Boeve Bradley F , Ju Yo-El S , Lim Miranda M ,   North American Prodromal Synucleinopathy (NAPS) Consortium, Ju Yo-El S , Boeve Bradley F , Postuma Ronald B , Avidan Alon Y , Bliwise Donald L , Criswell Susan R , Duff Kevin M , During Emmanuel H , Elliott Jonathan E , Fields Julie A , Forsberg Leah K , Gagnon Jean-François , Gan-Or Ziv , Howell Michael J , Huddleston Daniel E , Lee-Iannotti Joyce K , Lim Miranda M , Locke Jessica , Miglis Mitchell G , Neilson Lee E , Postuma Ronald B , Ross Owen A , Shprecher David R , Louis Erik K St , Videnovic Aleksandar , McLeland Jennifer , Amudson-Huffmaster Sommer , Brushaber Nellie , Choudhury Parichita , Chung Jae Woo , De Kam Joshua , Fischbach Ellen , Ekelmans Adrian , Keane Marissa , Keil Allison T , Kraft Ruth , Ligman Brittany R , Liu Lang , MacKinnon Colum , Miner-Rose Daeva , Murphy Samantha , Olivo Cosette , Pelletier Amelie , Powers Katherine L M , Stauder Matthew , Rivera Adreanne , Sanchez Sarahmay , Summers Rebekah , Tiegan Luke , Taylor Leah , Timm Paul , Tucker Kelsey , Yu Erik , Tran Peter , Galasko Douglas , Mignot Emmanuel , Schenck Carlos 
Published: January 2024

Abstract

Study Objectives
Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson’s disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)—henceforth “neurotrauma” (NT)—increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD.

Methods
Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory, and autonomic function, were completed. This cross-sectional analysis compared cases (n = 24; RBD + NT) to controls (n = 96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years).

Results
RBD + NT reported earlier RBD symptom onset (37.5 ± 11.9 vs. 52.2 ± 15.1 years of age) and a more severe RBD phenotype. Similarly, RBD + NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed.

Conclusions
This cross-sectional, matched case:control study shows individuals with RBD + NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD + NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process.