NAPS2 Clinical Core

ABSTRACT: NAPS2 CLINICAL CORE The North American Prodromal Synculeinopathy Consortium for RBD, Stage 2 (NAPS2) protocol represents an expanded and integrated international research consortium focused on RBD involving eight cores and one project. NAPS2 is designed to substantially and comprehensively increase the longitudinal clinical and biomarker (blood, CSF, PSG, MRI, DaTscan) data that will be available for research of RBD by internal and external investigators, with the goal of ultimately fostering the development of disease-modifying therapies targeting those with RBD to delay or prevent the development of overt DLB, PD or MSA. The current NAPS protocol (R34 AG056639, hereafter NAPS1) is a 2-year clinical trial planning grant that has successfully enrolled >200 participants with PSG-proven RBD across 10 sites. A comprehensive standardized set of clinical and neurocognitive measures is obtained for each participant, and includes the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set Version 3, the Lewy Body Dementia Module and other specific measures more relevant to PD and MSA. Biofluid samples that include DNA and plasma on all, and CSF on a subset, have been collected, transferred and processed at National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD). These data contribute to key genetic and biofluid markers that have been associated with RBD and that warrant further investigation. The PSG data from NAPS1 have been analyzed centrally, with REM sleep without atonia quantitative measures now developed; PSGs will be performed in NAPS2 and key data will be uploaded to the National Sleep Research Resource (NSRR). There was insufficient funding to perform neuroimaging studies across all of the sites in NAPS1, but MRI and DaTscan imaging data collected at a few of the centers resulted in promising preliminary findings and establish the basis for the inclusion of imaging in NAPS2; these scans will be uploaded to the Laboratory of Neuroimaging (LONI). The NAPS2 Clinical Core will build on the obvious success of the NAPS1 program by recruiting a large cohort of RBD participants (N>300) and evaluating them annually in a comprehensive and standardized manner. A smaller cohort of age- and sex-matched healthy controls will also be evaluated for comparative analyses in specific Cores and for the Project. The Prodromal Synucleinopathy Rating Scale for use in RBD-related research and clinical trials will also be developed. In anticipation for more widespread population screening and assessment, some novel virtual and digital measures in select RBD patients and controls will be piloted. Advanced directive for autopsy will also be sought for all RBD participants. The Clinical Core will therefore acquire high quality clinical data, biofluid samples, PSG data, and MRI and DaTscan imaging data to be integrated for use in all Cores and the Project and shared with the scientific community, as well as explore additional analyses in anticipation of future disease-modifying clinical trials.