Diagnostic Thresholds for REM Sleep Without Atonia in Idiopathic/Isolated REM Sleep Behavior Disorder in the North American Prodromal Synucleinopathy (NAPS) Cohort (1322)

Objective: We analyzed REM sleep without atonia (RSWA) between idiopathic/isolated REM sleep behavior disorder (iRBD) patients across participating NAPS sleep centers, compared to normative controls, and hypothesized that previous diagnostic RSWA thresholds were overestimates. Background: iRBD is a prodromal alpha-synucleinopathy characterized by dream enactment behavior and RSWA. We sought to define quantitative RSWA diagnostic thresholds in the North American Prodromal Synucleinopathy (NAPS) Consortium cohort. Design/Methods: All digital polysomnography files were converted to European Data Format and scored at a central laboratory (Mayo Clinic) which standardized display scoring montages, channel sensitivities, and filtering, and scripted computational analyses for visual scoring. RSWA was quantitatively analyzed in the submentalis (SM) and anterior tibialis (AT) muscles in iRBD (n=86) patients and controls (n=118) utilizing well validated visual (Mayo) and automated (RAI) methods. Parametric statistics were used to compare RSWA metrics, and RSWA thresholds were developed using receiver operating characteristic curves. Results: RSWA was significantly higher for the RAI and all visual individual and combined muscle activity metrics in iRBD compared to controls (all p Conclusions: RSWA thresholds in the NAPS cohort were substantially lower than previously reported, suggesting previously overestimated diagnostic RSWA thresholds due to smaller, enriched patient samples and overfit statistical modeling. Confirmation of these findings in the complete NAPS cohort (n=300 iRBD patients across all 10 NAPS centers) is planned. Disclosure: Mr. Feemster has nothing to disclose. Paul Timm has nothing to disclose. Luke Teigen has nothing to disclose. Sarah Faber has nothing to disclose. Tyler Steele has nothing to disclose. Sonia Rivera has nothing to disclose. Dr. McCarter has received personal compensation in the range of $0-$499 for serving as a Contributor with Medlink Neurology. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Biogen. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Alector. Dr. Boeve has received publishing royalties from a publication relating to health care. Kristina Hedtkamp has nothing to disclose. The institution of Dr. Ju has received research support from National Institutes of Health. Ms. McLeland has nothing to disclose. Dr. Postuma has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche, Biogen, Takeda, Theranexus, GE, Jazz, Curasen. Dr. Postuma has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen/Partners. The institution of Dr. Postuma has received research support from CIHR, Weston Foundation, Webster Foundation, Roche, MJFF, Parkinson Canada, FRSQ. Ms. Pelletier has nothing to disclose. Dr. Avidan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Avidan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadel. Dr. Avidan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Avidan has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Dr. Avidan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Avidan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Harmony. Dr. Avidan has received publishing royalties from a publication relating to health care. Adreanne Rivera has nothing to disclose. Donald Biwise has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Donald Biwise has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Donald Biwise has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Huxley. Donald Biwise has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ferring. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. St. Louis has received publishing royalties from a publication relating to health care.