Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

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.

Authors

Institutions

Publication Details

Journal
npj Parkinson s Disease
Published
2024-09-27
DOI
https://doi.org/10.1038/s41531-024-00789-w
Citations
27
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
9.97

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

Michael C. Brumm, Catherine Kopil, Billy Dunn, Lana M. Chahine et al.
27 citations
npj Parkinson s Disease
Parkinson's Disease Mechanisms and Treatments
9.97
article

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

Michael C. Brumm, Catherine Kopil, Billy Dunn, Lana M. Chahine, John Seibyl, Daniel A. Weintraub, Luis Concha‐Marambio, Danna Jennings, Tatiana Foroud, Caroline M. Tanner, Gennaro Pagano, Kathleen L. Poston, Kalpana Merchant, Thomas J. Montine, Matthew Stern, Kelly Nudelman, Tanya Simuni, Diane T. Stephenson, Andrew D. Siderowf, Eduardo Tolosa, Sohini Chowdhury, Brit Mollenhauer, Claudio Soto, Mark Frasier, Todd Sherer, Tien Dam, Peter DiBiaso, Caroline Gochanour, Andrew B. Singleton, Christopher S. Coffey, Yuge Xiao, Karl Kieburtz, Kenneth Marek
article en
27 citations

Abstract

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.

npj Parkinson s DiseaseVol. 10(1)
Rutgers, The State University of New Jersey (US), Northwestern University (US), University of Southern California (US), Roche (Switzerland) (CH), University of Iowa (US), Mount Sinai Beth Israel (US), Montreal Neurological Institute and Hospital (CA), Biogen (United States) (US), National Institutes of Health (US), Milken Institute (US), Cleveland Clinic (US), University of Salerno (IT), Barrow Neurological Institute (US), Innsbruck Medical University (AT), Johns Hopkins University (US), Radboud University Nijmegen (NL), Emory University (US), Philipps University of Marburg (DE), Oregon Health & Science University (US), Queen Mary University of London (GB), University of Pittsburgh (US), Duke University (US), University of California, San Francisco (US), Baylor College of Medicine (US), University of Luxembourg (LU), University of Lagos (NG), National and Kapodistrian University of Athens (GR), University of Washington (US), University of South Florida (US), University of Michigan (US), Toronto Western Hospital (CA), Columbia University Irving Medical Center (US), Tel Aviv Sourasky Medical Center (IL), Lou Ruvo Brain Institute (US), Ottawa Hospital (CA), Critical Path Institute (US), Johnson University (US), Banner Health (US), Michael J. Fox Foundation (US), John Radcliffe Hospital (GB), University of Rochester Medical Center (US), University of Alabama at Birmingham (US), University of Florida (US), University of California San Diego (US), NYU Langone Health (US), Massachusetts General Hospital (US), Denali Therapeutics (United States) (US), Biogipuzkoa Health Research Institute (ES), Institute for Neurodegenerative Disorders (US), Amprion (United States) (US), Hospital Clínic de Barcelona (ES), Universitätsmedizin Göttingen (DE), Mental Illness Research, Education and Clinical Centers (US), Paracelsus Elena Klinik Kassel (DE), Mayo Clinic in Arizona (US), Parkinson's Research and Education Foundation (US), University of Kansas Medical Center (US), Clinical Solutions (US), National Institute on Aging (US), Banner Sun Health Research Institute (US), Newcastle Hospitals - Campus for Ageing and Vitality (GB), Biogen (Italy) (IT), The University of Texas Health Science Center (US), International Neuromodulation Society (US), Imperial College London (GB), University of Colorado Anschutz Medical Campus (US), Indiana University – Purdue University Indianapolis (US), University of Cincinnati (US), University of Pennsylvania (US), University of Tübingen (DE), University of Colorado Denver (US), University of Lübeck (DE), Stanford University (US)
Michael J. Fox Foundation for Parkinson's Research, Eli Lilly and Company, Sanofi, Massachusetts General Hospital, Biogen, Alexion Pharmaceuticals, International Parkinson and Movement Disorder Society, Parkinson's Foundation, Acorda Therapeutics, Prothena, Scheme for Promotion of Academic and Research Collaboration, National Institutes of Health, School of Medicine, Stanford University, Weill Cornell Medical College, National Institute of Neurological Disorders and Stroke
Openalex Percentile: Top 1%
Parkinson's Disease Mechanisms and Treatments
9.97
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.