Frontiers in Neuroscience (Dec 2021)

Hoehn and Yahr Stage and Striatal Dat-SPECT Uptake Are Predictors of Parkinson’s Disease Motor Progression

  • Holly Jackson,
  • Holly Jackson,
  • Judith Anzures-Cabrera,
  • Kirsten I. Taylor,
  • Kirsten I. Taylor,
  • Gennaro Pagano,
  • Gennaro Pagano,
  • PASADENA Investigators,
  • Prasinezumab Study Group,
  • Claudia Altendorf,
  • Chareyna Anandan,
  • Giulia Andrews,
  • Solène Ansquer,
  • Raphaele Arrouasse,
  • Sana Aslam,
  • Jean-Philippe Azulay,
  • Jeanette Baker,
  • Ernest Balaguer Martinez,
  • Shadi Barbu,
  • Kara Bardram,
  • Danny Bega,
  • Helena Bejr-Kasem Marco,
  • Isabelle Benatru,
  • Eve Benchetrit,
  • Felix Bernhard,
  • Amir Besharat,
  • Sagari Bette,
  • Amelie Bichon,
  • Andrew Billnitzer,
  • Sophie Blondeau,
  • Thomas Boraud,
  • Freiderike Borngräber,
  • James Boyd,
  • Kathrin Brockmann,
  • Matthew Brodsky,
  • Ethan Brown,
  • Christof Bruecke,
  • Fabienne Calvas,
  • Monica Canelo,
  • Federico Carbone,
  • Claire Carroll,
  • Laura Casado Fernandez,
  • Catherine Cassé-Perrot,
  • Anna Castrioto,
  • Helene Catala,
  • Justine Chan,
  • Samia Cheriet,
  • Anthony Ciabarra,
  • Joseph Classen,
  • Juliana Coleman,
  • Robert Coleman,
  • Yaroslau Compta,
  • Anne-Gaëlle Corbillé,
  • Jean-Christophe Corvol,
  • Mariana Cosgaya,
  • Nabila Dahodwala,
  • Philippe Damier,
  • Elodie David,
  • Thomas Davis,
  • Marissa Dean,
  • Berengere Debilly,
  • Janell DeGiorgio,
  • Andres Deik,
  • Laure Delaby,
  • Marie-Helene Delfini,
  • Pascal Derkinderen,
  • Philipp Derost,
  • Maria de Toledo,
  • Lisa Deuel,
  • Ann Marie Diaz-Hernandez,
  • Cameron Dietiker,
  • Karina Dimenshteyn,
  • Julio Dotor,
  • Franck Durif,
  • Jens Ebentheuer,
  • Karla Maria Eggert,
  • Sara Eichau Madueño,
  • Claudia Eickhoff,
  • Aaron Ellenbogen,
  • Philipp Ellmerer,
  • Ines Esparragosa Vazquez,
  • Alexandre Eusebio,
  • Siobhan Ewert,
  • John Fang,
  • Danielle Feigenbaum,
  • Frederique Fluchere,
  • Alexandra Foubert-Samier,
  • Marie Fournier,
  • Anne Fradet,
  • Valerie Fraix,
  • Samuel Frank,
  • Franca Fries,
  • Monique Galitzky,
  • Marisol Gallardó Pérez,
  • Jose Manuel García Moreno,
  • Carmen Gasca,
  • Thomas Gasser,
  • Joyce Gibbons,
  • Caroline Giordana,
  • Alicia Gonzalez Martinez,
  • Ira Goodman,
  • Arantza Gorospe,
  • Marie Goubeaud,
  • David Grabli,
  • Mangone Graziella,
  • Stephan Grimaldi,
  • Jeffrey Gross,
  • Raquel Guimaraes-Costa,
  • Andreas Hartmann,
  • Christian Hartmann,
  • Travis Hassell,
  • Robert Hauser,
  • Antonio Hernandez,
  • Jorge Hernandez-Vara,
  • Guenter Hoeglinger,
  • Christian Homedes,
  • Andrea Horta-Barba,
  • Jean-Luc Houeto,
  • Julius Huebl,
  • Jennifer Hui,
  • Stuart Isaacson,
  • Joseph Jankovic,
  • Annette Janzen,
  • Junior Jauregui,
  • Jocelyne Jiao,
  • Maria Jose Marti Domenech,
  • Xavier Joseph,
  • Srinath Kadimi,
  • Pat Kaminski,
  • Silja Kannenberg,
  • Jan Kassubek,
  • Maya Katz,
  • Kevin Klos,
  • Shannon Klos,
  • Christopher Kobet,
  • Jennifer Koebert,
  • Patricia Krause,
  • Andrea Kuehn,
  • Jaime Kulisevsky Bojarsky,
  • Rajeev Kumar,
  • Martin Kunz,
  • Lille Kurvits,
  • Kimberly Kwei,
  • Simon Laganiere,
  • Brice Laurens,
  • Johannes Levin,
  • Oren Levy,
  • Peter LeWitt,
  • Gurutz Linazasoro Cristóbal,
  • Irene Litvan,
  • Karlo Lizarraga,
  • Katherine Longardner,
  • Rocio Lopez,
  • Lydia Lopez Manzanares,
  • Sara Lucas del Pozo,
  • Maria Rosario Luquin Puido,
  • Nijee Luthra,
  • Kelly Lyons,
  • Sylvia Maass,
  • Gerrit Machetanz,
  • Yolanda Macias,
  • David Maltete,
  • Jorge Uriel Manez Miro,
  • Louise-Laure Mariani,
  • Juan Marin,
  • Kathrin Marini,
  • Ana Marques,
  • Gloria Marti,
  • Maria Jose Marti Domenech,
  • Saul Martinez,
  • Wassilios Meissner,
  • Sara Meoni,
  • Brit Mollenhauer,
  • Dunia Mon Martinez,
  • Johnson Moon,
  • Elena Moro,
  • Peter Morrison,
  • Christoph Muehlberg,
  • Manpreet Multani,
  • Christine Murphy,
  • Anthony Nicholas,
  • Rajesh Pahwa,
  • Antonio Palasi,
  • Heidi Pape,
  • Neepa Patel,
  • Prity Patel,
  • Marina Peball,
  • Elizabeth Peckham,
  • Terry Peery,
  • Rafael Perez,
  • Jesus Perez,
  • Alisa Petit,
  • Elmar Pinkhardt,
  • Werner Poewe,
  • Elsa Pomies,
  • Cecile Preterre,
  • Joseph Quinn,
  • Olivier Rascol,
  • Philippe Remy,
  • Irene Richard,
  • Benjamin Roeben,
  • Emily Ruether,
  • Jost-Julian Rumpf,
  • David Russell,
  • Hayet Salhi,
  • Daniela Samaniego-Toro,
  • Alexandra Samier-Foubert,
  • Antonio Sanchez,
  • Emmanuelle Schmitt,
  • Alfons Schnitzler,
  • Oliver Schorr,
  • Julie Schwartzbard,
  • Kerstin Schweyer,
  • Klaus Seppi,
  • Victoria Sergo,
  • Holly Shill,
  • Andrew Siderowf,
  • Tanya Simuni,
  • Umberto Spampinato,
  • Ashok Sriram,
  • Natividad Stover,
  • Caroline Tanner,
  • Arjun Tarakad,
  • Carolyn Taylor,
  • Claire Thalamus,
  • Thomas Toothaker,
  • Nadege Van Blercom,
  • Nora Vanegas-Arrogave,
  • Lydia Vela,
  • Sylvian Vergnet,
  • Tiphaine Vidal,
  • Jonathan Vöglein,
  • Ryan Walsh,
  • Cheryl Waters,
  • Mirko Wegscheider,
  • Endy Weidinger,
  • Caroline Weill,
  • Gregor Wenzel,
  • Tatiana Witjas,
  • Isabel Wurster,
  • Brenton Wright,
  • Milan Zimmermann,
  • Rafael Zuzuarregui,
  • Markus Abt,
  • Atieh Bamdadian,
  • Teresa Barata,
  • Nicholas Barbet,
  • Sara Belli,
  • Frank Boess,
  • Azad Bonni,
  • Edilio Borroni,
  • Anne Boulay,
  • Markus Britschgi,
  • Jerome Chague,
  • Valerie Cosson,
  • Christian Czech,
  • Dennis Deptula,
  • Cheikh Diack,
  • Rachelle Doody,
  • Juergen Dukart,
  • Giulia D’Urso,
  • Sebastian Dziadek,
  • Hannah Eddleston,
  • Chris Edgar,
  • Laurent Essioux,
  • Morgan Farell,
  • Rebecca Finch,
  • Paulo Fontoura,
  • Waltraud Gruenbauer,
  • Andrea Hahn,
  • Stefan Holiga,
  • Michael Honer,
  • Shirin Jadidi,
  • Kelly Johnson-Wood,
  • Markus Keller,
  • Timothy Kilchenmann,
  • Martin Koller,
  • Thomas Kremer,
  • Thomas Kustermann,
  • Claire Landsdall,
  • Michael Lindemann,
  • Florian Lipsmeier,
  • Cecile Luzy,
  • Marianne Manchester,
  • Maddalena Marchesi,
  • Ferenc Martenyi,
  • Meret Martin-Facklam,
  • Katerina Mironova,
  • Annabelle Monnet,
  • Emma Moore,
  • Daniel K Ness,
  • Markus Niggli,
  • Tania Nikolcheva,
  • Susanne Ostrowitzki GP,
  • Benedicte Passmard,
  • Agnes Poirier,
  • Anke Post,
  • Megana Prasad,
  • Nathalie Pross,
  • Tiffany Quock,
  • Benedicte Ricci,
  • Ellen Rose,
  • Christoph Sarry,
  • Christine Schubert,
  • Dennis Selkoe,
  • Jeff Sevigny,
  • Kaycee Sink,
  • Hannah Staunton,
  • Tim Steven,
  • Alexander Strasak,
  • Hanno Svoboda KT,
  • Radhika Tripuraneni,
  • Dylan Trundell,
  • Daniel Umbricht,
  • Lynne Verselis,
  • Annamarie Vogt,
  • Ekaterina Volkova-Volkmar,
  • Cornelia Weber,
  • Silke Weber,
  • Wagner Zago

DOI
https://doi.org/10.3389/fnins.2021.765765
Journal volume & issue
Vol. 15

Abstract

Read online

Currently, no treatments available for Parkinson’s disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson’s Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.

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