Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
02
04
2024
accepted:
20
08
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
27
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39333167
doi: 10.1038/s41531-024-00789-w
pii: 10.1038/s41531-024-00789-w
doi:
Types de publication
Journal Article
Langues
eng
Pagination
178Investigateurs
Caroline Tanner
(C)
Douglas Galasko
(D)
Lana Chahine
(L)
Kathleen Poston
(K)
Roseanne Dobkin
(R)
None Dan Weintraub
Ethan Brown
(E)
Roy Alcalay
(R)
Aleksandar Videnovic
(A)
Duygu Tosun-Turgut
(D)
Werner Poewe
(W)
Susan Bressman
(S)
None Jan Hammer
Raymond James
(R)
Ekemini Riley
(E)
Leslie Shaw
(L)
David Standaert
(D)
Sneha Mantri
(S)
Nabila Dahodwala
(N)
Michael Schwarzschild
(M)
Connie Marras
(C)
Hubert Fernandez
(H)
Ira Shoulson
(I)
Helen Rowbotham
(H)
Paola Casalin
(P)
Claudia Trenkwalder
(C)
Jamie Eberling
(J)
Katie Kopil
(K)
Alyssa O'Grady
(A)
Maggie McGuire Kuhl
(MM)
Leslie Kirsch
(L)
Tawny Willson
(T)
Emily Flagg
(E)
Bridget McMahon
(B)
Craig Stanley
(C)
Kim Fabrizio
(K)
Dixie Ecklund
(D)
Trevis Huff
(T)
Laura Heathers
(L)
Christopher Hobbick
(C)
Gena Antonopoulos
(G)
Chelsea Caspell-Garcia
(C)
Michael Brumm
(M)
Arthur Toga
(A)
Karen Crawford
(K)
Jan Hamer
(J)
Doug Galasko
(D)
Thomas Montine
(T)
Carlie Tanner
(C)
Roseann Dobkin
(R)
Monica Korell
(M)
Charles Adler
(C)
Amy Amara
(A)
Paolo Barone
(P)
Bastiaan Bloem
(B)
Susan Bressman
(S)
Kathrin Brockmann
(K)
Norbert Brüggemann
(N)
Kelvin Chou
(K)
Alberto Espay
(A)
Stewart Factor
(S)
Michelle Fullard
(M)
Robert Hauser
(R)
Penelope Hogarth
(P)
Shu-Ching Hu
(SC)
Michele Hu
(M)
Stuart Isaacson
(S)
Christine Klein
(C)
Rejko Krueger
(R)
Mark Lew
(M)
Zoltan Mari
(Z)
Maria Jose Martí
(MJ)
Nikolaus McFarland
(N)
Tiago Mestre
(T)
Emile Moukheiber
(E)
Alastair Noyce
(A)
Wolfgang Oertel
(W)
Njideka Okubadejo
(N)
Sarah O'Shea
(S)
Rajesh Pahwa
(R)
Nicola Pavese
(N)
Ron Postuma
(R)
Giulietta Riboldi
(G)
Lauren Ruffrage
(L)
Javier Ruiz Martinez
(JR)
David Russell
(D)
Marie H Saint-Hilaire
(MH)
Neil Santos
(N)
Wesley Schlett
(W)
Ruth Schneider
(R)
Holly Shill
(H)
David Shprecher
(D)
Leonidas Stefanis
(L)
Yen Tai
(Y)
Arjun Tarakad
(A)
Susan Ainscough
(S)
Courtney Blair
(C)
Erica Botting
(E)
Isabella Chung
(I)
Kelly Clark
(K)
Ioana Croitoru
(I)
Kelly DeLano
(K)
Iris Egner
(I)
Fahrial Esha
(F)
May Eshel
(M)
Frank Ferrari
(F)
Victoria Kate Foster
(VK)
Alicia Garrido
(A)
Madita Grümmer
(M)
Bethzaida Herrera
(B)
Ella Hilt
(E)
Chloe Huntzinger
(C)
Farah Kausar
(F)
Christos Koros
(C)
Yara Krasowski
(Y)
Dustin Le
(D)
Ying Liu
(Y)
Taina M Marques
(TM)
Helen Mejia Santana
(HM)
Sherri Mosovsky
(S)
Jennifer Mule
(J)
Philip Ng
(P)
Lauren O'Brien
(L)
Abiola Ogunleye
(A)
Oluwadamilola Ojo
(O)
Obi Onyinanya
(O)
Lisbeth Pennente
(L)
Romina Perrotti
(R)
Michael Pileggi
(M)
Ashwini Ramachandran
(A)
Deborah Raymond
(D)
Jamil Razzaque
(J)
Shawna Reddie
(S)
Kori Ribb
(K)
Kyle Rizer
(K)
Janelle Rodriguez
(J)
Stephanie Roman
(S)
Clarissa Sanchez
(C)
Cristina Simonet
(C)
Anisha Singh
(A)
Elisabeth Sittig
(E)
Barbara Sommerfeld
(B)
Angela Stovall
(A)
Bobbie Stubbeman
(B)
Alejandra Valenzuela
(A)
Catherine Wandell
(C)
Diana Willeke
(D)
Karen Williams
(K)
Dilinuer Wubuli
(D)
Informations de copyright
© 2024. The Author(s).
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