TY - JOUR
T1 - Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts
AU - Dam, Tien
AU - Pagano, Gennaro
AU - Brumm, Michael C.
AU - Gochanour, Caroline
AU - Poston, Kathleen L.
AU - Weintraub, Daniel
AU - Chahine, Lana M.
AU - Coffey, Christopher
AU - Tanner, Caroline M.
AU - Kopil, Catherine M.
AU - Xiao, Yuge
AU - Chowdhury, Sohini
AU - Concha-Marambio, Luis
AU - DiBiaso, Peter
AU - Foroud, Tatiana
AU - Frasier, Mark
AU - Jennings, Danna
AU - Kieburtz, Karl
AU - Merchant, Kalpana
AU - Mollenhauer, Brit
AU - Montine, Thomas J.
AU - Nudelman, Kelly
AU - Seibyl, John
AU - Sherer, Todd
AU - Singleton, Andrew
AU - Stephenson, Diane
AU - Stern, Matthew
AU - Soto, Claudio
AU - Tolosa, Eduardo
AU - Siderowf, Andrew
AU - Dunn, Billy
AU - Simuni, Tanya
AU - Marek, Kenneth
AU - Wubuli, Dilinuer
AU - Williams, Karen
AU - Willeke, Diana
AU - Wandell, Catherine
AU - Valenzuela, Alejandra
AU - Stubbeman, Bobbie
AU - Stovall, Angela
AU - Sommerfeld, Barbara
AU - Sittig, Elisabeth
AU - Singh, Anisha
AU - Simonet, Cristina
AU - Sanchez, Clarissa
AU - Roman, Stephanie
AU - Rodriguez, Janelle
AU - Rizer, Kyle
AU - Ribb, Kori
AU - Marques, Taina M.
AU - Statistics Core
AU - Imaging Core
AU - Screening Core
AU - Data Management Core
AU - Strategy and Technical Operations
AU - Site Management Core
AU - Study Cores, Committees, and Related Studies
AU - Michael J. Fox Foundation (Sponsor)
AU - Steering Committee
AU - Executive Steering Committee
AU - Project Management Core
AU - the Parkinson’s Progression Markers Initiative
AU - Coordinators
AU - Site Investigators
AU - PPMI Online
AU - Found
AU - Pathology Core
AU - Genetics Core
AU - Biologics Review Committee
AU - Biorepository Core
AU - Bioinformatics Core
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.
AB - The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.
UR - https://www.scopus.com/pages/publications/85205695610
U2 - 10.1038/s41531-024-00789-w
DO - 10.1038/s41531-024-00789-w
M3 - Article
C2 - 39333167
AN - SCOPUS:85205695610
SN - 2373-8057
VL - 10
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
IS - 1
M1 - 178
ER -