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
Jonathan E. Elliott, Brittany R. Ligman, Mohini Bryant‐Ekstrand, Allison Keil, Katherine Powers, Cosette Olivo, Lee E. Neilson, Ronald B. Postuma, Amélie Pelletier, Jean‐François Gagnon, Ziv Gan‐Or, Eric Yu, Lang Liu, Erik K. St. Louis, Leah K. Forsberg, Julie A. Fields, Owen A. Ross, Daniel E. Huddleston, Donald L. Bliwise, Alon Y. Avidan, Michael J. Howell, Carlos H. Schenck, Jennifer McLeland, Susan R. Criswell, Aleksandar Videnović, Emmanuel During, Mitchell G. Miglis, David Shprecher, Joyce Lee‐Iannotti, Bradley F. Boeve, Yo‐El S. Ju, Miranda M. Lim, Yo‐El S. Ju, Bradley F. Boeve, Ronald B. Postuma, Alon Y. Avidan, Donald L. Bliwise, Susan R. Criswell, Kevin Duff, Emmanuel During, Jonathan E. Elliott, Julie A. Fields, Leah K. Forsberg, Jean‐François Gagnon, Ziv Gan‐Or, Michael J. Howell, Daniel E. Huddleston, Joyce Lee‐Iannotti, Miranda M. Lim, Jessica Locke, Mitchell G. Miglis, Lee E. Neilson, Ronald B. Postuma, Owen A. Ross, David Shprecher, Erik K. St. Louis, Aleksandar Videnović, Jennifer McLeland, Sommer Amudson-Huffmaster, Nellie Brushaber, Parichita Choudhury, Jae Woo Chung, Joshua De Kam, Ellen Fischbach, Adrian Ekelmans, Marissa Keane, Allison Keil, Ruth Kraft, Brittany R. Ligman, Lang Liu, Colum D. MacKinnon, Daeva Miner-Rose, Samantha Murphy, Cosette Olivo, Amélie Pelletier, Katherine Powers, Matthew Stauder, Adreanne Rivera, Sarahmay Sanchez, Rebekah L. S. Summers, Luke Tiegan, Leah Taylor, Paul Timm, Kelsey Tucker, Erik Yu, Peter Tran, Douglas Galasko, Emmanuel Mignot, Carlos H. Schenck
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.