NAPS Aims

    1. Aim 1: To conduct research on RBD as a prodromal manifestation of DLB, PD, and MSA to address several of the NAPA ADRD priorities for LBD research as well as similar priorities for PD and MSA.  

    2. Aim 2: To expand our cohort of RBD participants and add matched control participants for longitudinal, standardized collection of clinical, PSG, genetic, biofluid, and neuroimaging data.  

    3. Aim 3: To analyze collected data against longitudinal clinical outcomes to refine scales and develop /analyze biomarkers to optimally design clinical trials.  

    4. Aim 4: To share data, samples, and methods for use by the scientific community.  

    5. Aim 5: To interact with NIH, other scientific groups on RBD and overt synucleinopathies, industry partners, patients, and other groups.  

    6. Aim 6: To prepare for large-scale clinical trials.

    1. Aim 1: Facilitate recruitment and retention of a diverse participant population into NAPS2. 

    2. Aim 2: Develop and implement educational initiatives and training opportunities centered on RBD REM Sleep Behavior Disorder Education Delivery (REMEDY). 

    3. Aim 3: Create and perform outreach activities aimed to 1) inform and raise awareness of lay individuals about RBD and related disorders while nurturing research participation, and 2) form strategic relationship with key stakeholders in the area of RBD and related disorders

    4. Aim 4: Evaluate the effectiveness of REO Core activities and programs. 

    1. Aim 1: To standardize and harmonize polysomnography (PSG) data collection across NAPS2 Sites,

    2. Aim 2: To rigorously and reliably quantify REM sleep without atonia (RSWA)

    3. Aim 3: To serve as a repository for all PSG data collected in NAPS2

    4. Aim 4: To explore the feasibility of alternative, non-laboratory methods for home-based PSG data collection, and to determine the technical adequacy of such methods for signal interpretation and RSWA analyses when compared to gold-standard laboratory-based PSG. 

    1. Aim 1: Establish and maintain harmonized MRI and SPECT acquisition protocols at all Sites.  

      1a: Establish and maintain harmonized acquisition protocols of T1, FLAIR, multi-echo T2* GRE, diffusion, and resting state functional MRI similar to the Alzheimer’s Disease Neuroimaging Initiative 3 protocol. 

      1b: Establish and maintain a neuromelanin-sensitive MRI (NM-MRI) protocol for assessment of SNc and LC. Use a magnetization transfer contrast approach that is sensitive to prodromal synucleinopathy effects and has high scan-rescan reproducibility. 

      1c: Establish and maintain harmonized DaTscan imaging drug delivery and acquisition protocols that are similar to those in the Parkinson’s Disease Progression Marker Initiative. 

    2. Aim 2: Operate a standardized quality control program for MRI and DaTscan, including ongoing image quality monitoring, rating and maintenance. 

      2a: Implement a standardized MRI quality control program.   

      2b: Implement a NM-MRI quality control program with ongoing rapid image processing to allow contrast quality monitoring.  

      2c: Implement a standardized quality control program for DaTscan.  

    3. Aim 3: Supply processed cross-sectional and longitudinal data on serial MRIs and DaTscans for the Project, and share these data with the research community while protecting patient confidentiality. 

      3a: Cross-sectional and longitudinal analysis of basal forebrain and brainstem nuclei volumes and cortical thickness will be performed. 

      3b: Cross-sectional and longitudinal measurement of 1) LC and SNc neuromelanin volumes and 2) iron accumulation in the NM-MRI defined SNc. Reproducible, automated image processing will be used. 

      3c: Cross-sectional and longitudinal analysis of striatal uptake seen on DaTscan will be performed. 

      3d: Sharing of anonymized imaging data with the research community in collaboration with LONI. 

    1. Aim 1: Perform whole genome sequencing (WGS) to determine genomic architecture of those with RBD and assess ethnicity and relatedness between NAPS2 participants.  

    2. Aim 2: Perform GWAS and generate polygenic risk score (PRS) for NAPS2.

    3. Aim 3: Perform targeted gene and pathway analyses.  

    1. Aim 1: Coordinate all NAPS2 Cores, Sites, Project, personnel, and resources.

    2. Aim 2: Facilitate communication within and outside of NAPS.

    3. Aim 3: Safeguard data quality and consistency across the NAPS Consortium.

    4. Aim 4: Promote research in RBD.

    5. Aim 5: Guarantee compliance with required regulatory bodies.

    1. Aim 1: To recruit and evaluate patients with PSG-confirmed RBD in a comprehensive and longitudinal manner. 

    2. Aim 2: To ensure that high quality clinical data, biofluid samples, PSG data, and neuroimaging data are integrated for use in all cores and projects, and shared with the broader scientific community. 

    3. Aim 3: To refine and validate the Prodromal Synucleinopathy Rating Scale for use in RBD-related research and clinical trials. 

    4. Aim 4: To test virtual and digital measures in a Pilot Study. 

    5. Aim 5: To obtain and coordinate advanced directive for autopsy among willing RBD participants. 

    1. Aim 1: Oversee biofluid specimen collection, processing, and storage.

    2. Aim 2: Perform assays for established neurodegenerative biomarkers.

    3. Aim 3: Develop new synucleinopathy biomarkers by supporting collaborations with internal and external investigators.

    1. Aim 1: Clinical data management. To design clinical data forms and integrate the existing NAPS1 and prospective NAPS2 data into a combined database in Medidata RAVE® that shares a standardized database dictionary (with Clinical and Administrative Cores).  

    2. Aim 2: Enrollment tracking and QC. To coordinate with Clinical and Administrative Cores to track enrollment and procedures, oversee enrollment targets, and standardize data quality control (QC) processes at all NAPS2 Sites.  

    3. Aim 3: Integrated program-wide relational database. To integrate clinical, polysomnography (PSG), biofluid, neuroimaging, and genetic data (from Clinical, PSG, Biofluid, Neuroimaging, and Genetics Cores) in a SAS® relational database; perform cross-modalities QC, and conduct semi-annual data freezes (DF).  

    4. Aim 4: Distribution and sharing of data. To produce appropriately de-identified and statistically analyzable datasets for distribution to individual investigators and sharing with public data repositories. 

    5. Aim 5: Machine learning. To provide expertise on machine learning analysis of data across cores. 

    6. Aim 6: Statistical expertise. To provide statistical expertise including data analyses and report preparation for Cores and Project within NAPS2; support internal and external investigators using NAPS data; and provide statistical review of manuscripts and presentations based on NAPS data.  

    7. Aim 7: Clinical trial planning. To produce optimal estimates to key design parameters for future clinical trials in synucleinopathies including efficacy endpoints, sample sizes, power, rate of phenoconversion and length of intervention that are based on NAPS2 data. 

    1. Aim 1: To determine the degree and distribution of abnormalities in clinical measures, PSG and biofluid biomarkers among a large cohort of persons with RBD.  

    2.  Aim 2: To determine the conversion rate from RBD to an overt synucleinopathy, and to define predictive biomarkers of phenoconversion.  

    3.  Aim 3: To track change on clinical measures and biomarkers, in order to develop progression biomarkers of synucleinopathy. 

    4.  Aim 4: To combine data on phenoconversion, predictive biomarkers, and progression biomarkers to estimate sample size according to different patient selection criteria and primary outcomes for neuroprotective clinical trials in RBD.