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

Author

Holly Jackson, Judith Anzures-Cabrera, Kirsten I. Taylor, 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, 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, and Wagner Zago

Subjects
PASADENA, PPMI (Parkinson’s Progression Markers Initiative), Parkinson’s disease, progression predictors, ridge regression, disease stage, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

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.

Published
2021
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2. A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data

Author

Gennaro Pagano, Frank G. Boess, Kirsten I. Taylor, Benedicte Ricci, Brit Mollenhauer, Werner Poewe, Anne Boulay, Judith Anzures-Cabrera, Annamarie Vogt, Maddalena Marchesi, Anke Post, Tania Nikolcheva, Gene G. Kinney, Wagner M. Zago, Daniel K. Ness, Hanno Svoboda, Markus Britschgi, Susanne Ostrowitzki, Tanya Simuni, Kenneth Marek, Martin Koller, Jeff Sevigny, Rachelle Doody, Paulo Fontoura, Daniel Umbricht, Azad Bonni, 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, Günter Höglinger, 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, Saul Martinez, Wassilios Meissner, Sara Meoni, 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, 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, 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, Edilio Borroni, Jerome Chague, Valerie Cosson, Christian Czech, Dennis Deptula, Cheikh Diack, Juergen Dukart, Giulia D'Urso, Sebastian Dziadek, Hannah Eddleston, Chris Edgar, Laurent Essioux, Morgan Farell, Rebecca Finch, Waltraud Gruenbauer, Andrea Hahn, Stefan Holiga, Michael Honer, Shirin Jadidi, Kelly Johnson-Wood, Markus Keller, Timothy Kilchenmann, Thomas Kremer, Thomas Kustermann, Claire Landsdall, Michael Lindemann, Florian Lipsmeier, Cecile Luzy, Marianne Manchester, Ferenc Martenyi, Meret Martin-Facklam, Katerina Mironova, Annabelle Monnet, Emma Moore, Daniel K Ness, Markus Niggli, Benedicte Passmard, Agnes Poirier, Megana Prasad, Nathalie Pross, Tiffany Quock, Ellen Rose, Christoph Sarry, Christine Schubert, Dennis Selkoe, Kaycee Sink, Hannah Staunton, Tim Steven, Alexander Strasak, Kirsten Taylor, Radhika Tripuraneni, Dylan Trundell, Lynne Verselis, Ekaterina Volkova-Volkmar, Cornelia Weber, Silke Weber, and Wagner Zago

Subjects
Parkinson's disease, alpha-synuclein (α-syn), prasinezumab, monoclonal antibodies, disease progression, MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease.Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD.Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society—Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial Registration: NCT03100149.

Published
2021
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3. Health-Related Quality of Life Is Severely Affected in Primary Orthostatic Tremor

Author

Lucie Maugest, Eavan M. McGovern, Katia Mazalovic, Mohamed Doulazmi, Emmanuelle Apartis, Mathieu Anheim, Frédéric Bourdain, Eve Benchetrit, Virginie Czernecki, Emmanuel Broussolle, Cecilia Bonnet, Bruno Falissard, Marjan Jahanshahi, Marie Vidailhet, and Emmanuel Roze

Subjects
primary orthostatic tremor, movement disorder, progressive, health-related quality of life, mixed-method methodology, Neurology. Diseases of the nervous system, RC346-429
Abstract

BackgroundPrimary orthostatic tremor (POT) is a movement disorder characterized by unsteadiness upon standing still due to a tremor affecting the legs. It is a gradually progressive condition with limited treatment options. Impairments in health-related quality of life (HQoL) seem to far exceed the physical disability associated with the condition.MethodsA multi-center, mixed-methodology study was undertaken to investigate 40 consecutive patients presenting with POT to four movement disorder centers in France. HQoL was investigated using eight quantitative scales and a qualitative study which employed semi-structured interviews. Qualitative data were analyzed with a combination of grounded-theory approach.ResultsOur results confirm that HQoL in POT is severely affected. Fear of falling was identified as the main predictor of HQoL. The qualitative arm of our study explored our initial results in greater depth and uncovered themes not identified by the quantitative approach.ConclusionOur results illustrate the huge potential of mixed methodology in identifying issues influencing HQoL in POT. Our work paves the way for enhanced patient care and improved HQoL in POT and is paradigmatic of this modern approach for investigating HQoL issues in chronic neurological disorders.

Published
2018
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4. Primary progressive aphasias associated with C9orf72 expansions: Another side of the story

Author

idier Hannequin, Eino Solje, Sabrina Sayah, Emmanuel Gerardin, Marie Sarazin, Florence Pasquier, Marion Houot, Assi-Hervé Oya, Martine Vercelletto, Julien Lagarde, Marie Noguès-Lassiaille, Marie Chupin, Vincent Deramecourt, Sophie Auriacombe, Agnès Camuzat, Marc Teichmann, Jérémie Pariente, Sophie Ferrieux, Lucette Lacomblez, Mathieu Chastan, Jacques Monteil, Yaohua Chen, Marie-Paule Boncoeur, Lorenzo Cipriano, Anne Bissery, Simona Bottani, David Wallon, Christine Delmaire, Carole Roué-Jagot, Benjamin Le Toullec, Bernard-François Michel, Grégory Petyt, Olivier Martinaud, Philippe Couratier, Dario Saracino, Adeline Rollin-Sillaire, Daisy Rinaldi, Mira Didic, Serge Belliard, Amandine Géraudie, Géraldine Lautrette, Frédérique Etcharry-Bouyx, Xavier Delbeuck, Richard Levy, Frédéric Blanc, Mathieu Ceccaldi, Christel Thauvin-Robinet, Marie-Odile Habert, Eve Benchetrit, Maïté Formaglio, Alexis Brice, Isabelle Le Ber, Charles Duyckaerts, Véronique Golfier, Raffaella Migliaccio, Marie-Anne Mackowiak, Catherine Thomas-Antérion, Anne Bertrand, Olivier Colliot, François Sellal, Claire Boutoleau-Bretonnière, Anne M. Remes, Hugo Bertin, Aurélie Funkiewiez, and Stéphanie Bombois

Subjects
medicine.medical_specialty, C9orf72 Protein, Apraxias, Cognitive Neuroscience, Inferior frontal gyrus, Experimental and Cognitive Psychology, Frontotemporal lobar degeneration, respiratory system, Audiology, medicine.disease, Magnetic Resonance Imaging, Apraxia, Primary progressive aphasia, Aphasia, Primary Progressive, Neuropsychology and Physiological Psychology, Atrophy, C9orf72, medicine, Humans, Speech, Orbitofrontal cortex, Psychology, Language, Frontotemporal dementia
Abstract

C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them. This study depicts the spectrum of C9orf72–related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant. Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.

Published
2021

5. Personality Assessment with Temperament and Character Inventory in Parkinson's Disease

Author

Mathilde Boussac, Christophe Arbus, Olivier Colin, Chloé Laurencin, Alexandre Eusebio, Elodie Hainque, Jean Christophe Corvol, Nathalie Versace, Olivier Rascol, Vanessa Rousseau, Estelle Harroch, Fabienne Ory-Magne, Margherita Fabbri, Caroline Moreau, Anne-Sophie Rolland, Béchir Jarraya, David Maltête, Sophie Drapier, Ana-Raquel Marques, Nicolas Auzou, Thomas Wirth, Mylène Meyer, Bruno Giordana, Mélissa Tir, Tiphaine Rouaud, David Devos, Christine Brefel-Courbon, Pr Luc Defebvre, Dr Nicolas Carriere, Dr Guillaume Grolez, Dr Guillaume Baille, Dr Kreisler, Pr Jean-Pierre Pruvo, Pr Leclerc, Dr Renaud Lopes, Dr Romain Viard, Dr Gregory Kuchcinski, Mr Julien Dumont, Pr Kathy Dujardin, Mme M. Delliaux, Mrs M. Brion, Dr Gustavo Touzet, Pr Nicolas Reyns, Pr Arnaud Delval, Mrs Valerie Santraine, Mrs Marie Pleuvret, Mrs Nolwen Dautrevaux, Mr Victor Laugeais, Thavarak Ouk, Camille Potey, Celine Leclercq, Elise Gers, Jean-Christophe Corvol, null Marie-Vidailhet, Marie-Laure Welter, Lucette Lacomblez, David Grabli, Emmanuel Roze, Yulia Worbe, Cécile Delorme, Hana You, Jonas Ihle, Raquel Guimeraes-Costa, Florence Cormier-Dequaire, Aurélie Méneret, Andréas Hartmann, Louise-Laure Mariani, Stéphane Lehericy, Virginie Czernecki, Fanny Pineau, Frédérique Bozon, Camille Huiban, Eve Benchetrit, Carine Karachi, Soledad Navarro, Philippe Cornu, Arlette Welaratne, Carole Dongmo-Kenfack, Lise Mantisi, Nathalie Jarry, Sophie Aix, Carine Lefort, Dr Tiphaine Rouaud, Pr Philippe Damier, Pr Pascal Derkinderen, Dr Anne-Gaelle Corbille, Dr Elisabeth Calvier-Auffray, Mrs Laetitia Rocher, Mrs Anne-Laure Deruet, Dr Raoul Sylvie, Dr Roualdes Vincent, Mrs Le Dily Séverine, Dr Ana Marques, Dr Berangere Debilly, Pr Franck Durif, Dr Philippe Derost, Dr Charlotte Beal, Carine Chassain, Laure Delaby, Tiphaine Vidal, Pr Jean Jacques Lemaire, Isabelle Rieu, Elodie Durand, Pr Alexandre Eusebio, Pr Jean-Philippe Azulay, Dr Tatiana Witjas, Dr Frédérique Fluchère, Dr Stephan Grimaldi, Pr Nadine Girard, Marie Delfini, Dr Romain Carron, Pr Jean Regis, Dr Giorgio Spatola, Camille Magnaudet, Dr Ansquer Solène, Dr Benatru Isabelle, Dr Colin Olivier, Pr Houeto Jl, Pr Guillevin Remy, Mrs Fradet Anne, Mrs Anziza Manssouri, Mrs Blondeau Sophie, Dr Richard Philippe, Dr Cam Philippe, Dr Page Philippe, Pr Bataille Benoit, Mrs Rabois Emilie, Mrs Guillemain Annie, Dr Drapier Sophie, Dr Frédérique Leh, Dr Alexandre Bonnet, Pr Marc Vérin, Dr Jean-Christophe Ferré, Mr Jean François Houvenaghel, Pr Claire Haegelen, Mrs Francoise Kestens, Mrs Solenn Ory, Pr Pierre Burbaud, Dr Nathalie Damon-Perriere, Pr Wassilios Meissner, Pr Francois Tison, Dr Stéphanie Bannier, Dr Elsa Krim, Pr Dominique Guehl, Sandrine Molinier-Blossier, Morgan Ollivier, Marion Lacoste, Marie Bonnet, Pr Emmanuel Cuny, Dr Julien Engelhardt, Olivier Branchard, Clotilde Huet, Julie Blanchard, Pr Rascol Olivier, Dr Christine Brefel Courbon, Dr Fabienne Ory Magne, Dr Marion Simonetta Moreau, Pr Christophe Arbus, Pr Fabrice Bonneville, Dr Jean Albert Lotterie, Marion Sarrail, Charlotte Scotto d’Apollonia, Pr Patrick Chaynes, Pr François Caire, Pr David Maltete, Dr Romain Lefaucheur, Dr Damien Fetter, Dr Nicolas Magne, Mrs Sandrine Bioux, Mrs Maud Loubeyre, Mrs Evangéline Bliaux, Mrs Dorothée Pouliquen, Pr Stéphane Derrey, Mrs Linda Vernon, Dr Frédéric Ziegler, Mathieu Anheim, Ouhaid Lagha-Boukbiza, Christine Tranchant, Odile Gebus, Solveig Montaut, S. Kremer, Nadine Longato, Clélie Phillips, Jimmy Voirin, Marie des Neiges Santin, Dominique Chaussemy, Dr Amaury Mengin, Dr Caroline Giordana, Dr Claire Marsé, Lydiane Mondot, Robin Kardous, Bernadette Bailet, Héloise Joly, Denys Fontaine, Dr Aurélie Leplus, Amélie Faustini, Vanessa Ferrier, Pr Pierre Krystkowiak, Dr Mélissa Tir, Pr Jean-Marc Constans, Sandrine Wannepain, Audrey Seling, Dr Michel Lefranc, Stéphanie Blin, Béatrice Schuler, Pr Stephane Thobois, Dr Teodor Danaila, Dr Chloe Laurencin, Pr Yves Berthezene, Dr Roxana Ameli, Helene Klinger, Dr Gustavo Polo, Patrick Mertens, A. Nunes, Elise Metereau, Dr Lucie Hopes, Dr Solène Frismand, Dr Emmanuelle Schmitt, Mrs Mylène Meyer, Mrs Céline Dillier, Pr Sophie Colnat, Mrs Anne Chatelain, Dr Jean- Philippe Brandel, Dr Cécile Hubsch, Dr Patte Karsenti, Dr Marie Lebouteux, Dr Marc Ziegler, Dr Christine Delmaire, Dr Julien Savatowky, Mrs Juliette Vrillac, Mrs Claire Nakache, Dr Vincent D'Hardemare, Mr Lhaouas Belamri, Dr Valérie Mesnage, Dr Cécilia Bonnet, Dr Jarbas Correa Lino, Dr Camille Decrocq, Dr Anne Boulin, Mrs Inès Barre, Mrs Jordane Manouvrier, Dr Bérénice Gardel, Pr Béchir Jarraya, Mrs Catherine Ziz, Mrs Lydie Prette, Mr Hassen Douzane, David Gay, Robin Bonicel, Fouzia El Mountassir, Clara Fischer, Jean-François Mangin, Marie Chupin, Yann Cointepas, Bertrand Accart, Patrick Gelé, Florine Fievet, Matthieu Chabel, Virginie Derenaucourt, Loïc Facon, Yanick Tchantchou Njosse, Dominique Deplanque, Alain Duhamel, Lynda Djemmane, Florence Duflot, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier de Brive-la-Gaillarde (CH Brive), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Marseille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CIC - Biotherapie - Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Foch [Suresnes], Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Bordeaux [Bordeaux], Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by the France Parkinson charity and French Ministry of Health (PHRC national 2012). This is an ancillary study to Protocol ID: 2013-A00193-42, ClinicalTrials.gov: NCT02360683., Centre Hospitalier Brive-la-Gaillarde, and Hôpital P.P.-Riquet

Subjects
Personality Inventory, Temperament and character inventory, Parkinson's disease, Parkinson Disease, Personality Assessment, Antidepressive Agents, Neurology, Anti-Anxiety Agents, Fluctuating PD patients, Quality of Life, Humans, Neurology (clinical), Geriatrics and Gerontology, Temperament, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Personality
Abstract

International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.

Published
2022

6. Social Cognitive Impairment in Early Parkinson's Disease: a novel 'Mild Impairment'?

Author

Marie Vidailhet, Marion Houot, Virginie Czernecki, Jean-Christophe Corvol, Eve Benchetrit, Graziella Mangone, Richard Levy, Fanny Pineau, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Université de Montpellier (UM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Gestionnaire, HAL Sorbonne Université 5

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Parkinson's disease, Emotions, Theory of Mind, Audiology, Neuropsychological Tests, 03 medical and health sciences, Mild Social Cognition Impairment in PD Parkinson's disease, 0302 clinical medicine, Social cognition, Medicine, Humans, Apathy, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, business.industry, Cognitive disorder, Neuropsychology, Cognition, Parkinson Disease, Middle Aged, medicine.disease, MCI, 030104 developmental biology, Mood, Neurology, Social Perception, Anxiety, Female, emotional processes, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Introduction Social cognition (SC) deficit has recently been described in the early stages of Parkinson's disease (PD), but findings remain unclear. Our objective was to determine the frequency of SC impairment in newly-diagnosed PD patients and whether it is independent of Mild Cognitive Impairment (MCI). Methods We enrolled 109 patients with idiopathic PD diagnosed within the previous four years (ICEBERG cohort) and 39 healthy participants. SC was evaluated using the Mini-Social Cognition and Emotional Assessment (Mini-SEA) that allows a multi-domain assessment of SC. Relationships between SC and clinical characteristics, global cognitive efficiency, mood, anxiety, apathy and impulse control disorders, were also evaluated. Results 30% of patients had significant socio-emotional impairment. Moreover, SC deficit in isolation was 3.5 times more frequent than MCI in isolation (20.2% vs 5.5% respectively). Both emotion identification and Theory of Mind were impaired compared to healthy participants. No effect of age, level of education, disease severity, dopamine replacement therapy, or global cognitive efficiency were found. Only scores on the Frontal Assessment Battery were correlated with SC abilities. Conclusion SC impairment is frequent in early PD and should be given more consideration. It often occurs in the absence of any other cognitive disorder and may represent the most common neuropsychological deficit in early-stage PD. In line with the definition of PD-MCI criteria, we consider the addition of a sixth MCI sub-type termed “Mild Social Cognition Impairment (MSCI)”. Further studies are required to validate the addition of this new MCI domain.

Published
2021

7. Parkinson's disease polygenic risk score is not associated with impulse control disorders: A longitudinal study

Author

Vanessa Brochard, Fanny Artaud, Frédéric Bourdain, S. Sambin, Valérie Mesnage, O. Rascol, Clemens R. Scherzer, Fabienne Ory-Magne, Isabelle Rieu, Jean-Christophe Corvol, Fanny Pineau, Merry Mazmanian, Louise-Laure Mariani, Monica Roy, Hélène Bertrand, Marie Vidailhet, Graziella Mangone, Tiphaine Vidal, Benjamin Le Toullec, Bérangère Debilly, Sara Leder, Emmanuel Roze, Bertrand Degos, Samir Bekadar, Cecilia Bonnet, Genetic core: Alexis Brice, Jean-Philippe Brandel, Antoine Faurie-Grepon, Hana You, Monique Galitsky, Stephan Klebe, Julia Kraemmer, J. Ihle, Mostafa Hajji, Virginie Bayet, David Grabli, Richard Levy, P. Derkinderen, Hakima Manseur, Ll Mariani, Julie Socha, Suzanne Lesage, Florence Cormier-Dequaire, Statistical analyses, A. Marques, Fernando Pico, Khadija Tahiri, Andreas Hartmann, Stéphane Bernard, Olivier Rascol, Eve Benchetrit, Alexis Brice, Julia Muellner, F. Durif, Violaine Plante-Bordeneuve, Sponsor activities, J-C Corvol, Alain Mallet, Co-investigators, Coralie Villeret, Pascal Derkinderen, Franck Durif, Anne-Marie Bonnet, Neuropsychologists, Christine Brefel-Courbon, Mélissa Tir, A. Elbaz, Lucette Lacomblez, Alexis Elbaz, Elsa Pomies, F. Artaud, Principal investigators for sites, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), NS-Park/FCRIN Network, UMS 015, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Foch [Suresnes], Fondation A. Rothschild, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Henri Mondor, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANR-10-IAIHU-06 Ministère des Affaires Sociales et de la Santé: AOR0810 Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM: ANSM-2013, This project was funded by grants from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, AOR0810 ) and from the French Drug Agency (Agence Nationale de Sécurité et des Médicaments, ANSM-2013 ). The research leading to these results has received funding from the program ' Investissements d’Avenir ' ANR-10-IAIHU-06 . We want to express our gratitude to all the participants who made this study possible., ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Longitudinal study, Multifactorial Inheritance, Parkinson's disease, Movement disorders, Genome-wide association study, Disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Genetic predisposition, Humans, Longitudinal Studies, Age of Onset, Adverse effect, Generalized estimating equation, Aged, business.industry, Parkinson Disease, Middle Aged, medicine.disease, 3. Good health, Disruptive, Impulse Control, and Conduct Disorders, 030104 developmental biology, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), France, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

International audience; Objective: To examine the relationship between a Parkinson's disease (PD) polygenic risk score (PRS) and impulse control disorders (ICDs) in PD. Background: Genome wide association studies (GWAS) have brought forth a PRS associated with increased risk of PD and younger disease onset. ICDs are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. It is unknown whether ICDs and PD share genetic susceptibility. Methods: We used data from a multicenter longitudinal cohort of PD patients with annual visits up to 6 years (DIG-PD). At each visit ICDs, defined as compulsive gambling, buying, eating, or sexual behavior were evaluated by movement disorders specialists. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted PRS based on 90 SNPs associated with PD. We estimated the association between PRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for dopaminergic treatment and other known risk factors for ICDs. Results: Of 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p < 0.001) as well as higher PRS values (p = 0.06). At baseline, there was no association between the PRS and ICDs (overall, p = 0.84). The prevalence of ICDs increased over time similarly across the quartiles of the PRS (overall, p = 0.88; DA users, p = 0.99). Conclusion: Despite younger disease onset being associated with both higher PRS and ICD prevalence, our findings are not in favor of common susceptibility genes for PD and ICDs.

Published
2020

8. French validation of the questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale (QUIP-RS)

Author

Bruno Pereira, Hana You, Julie Socha, Jean-Christophe Corvol, Eve Benchetrit, Franck Durif, Alexis Elbaz, Ana Marques, Fanny Pineau, Elsa Pomies, Pascal Derkinderen, Tiphaine Vidal, Graziella Mangone, Florence Cormier, Monique Galitstky, Olivier Rascol, Daniel Weintraub, Fanny Artaud, Groupe de sociologie politique et morale (GSPM), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Délégation à la Recherche Clinique et à l'Innovation (DRCI), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurology, University of Pennsylvania [Philadelphia], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Pennsylvania, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, Parkinson's disease, Impulse control disorder, Psychometrics, Concordance, media_common.quotation_subject, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Rating scale, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, media_common, Aged, Language, Psychiatric Status Rating Scales, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Addiction, [SCCO.NEUR]Cognitive science/Neuroscience, Reproducibility of Results, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, Translating, medicine.disease, 3. Good health, Disruptive, Impulse Control, and Conduct Disorders, 030104 developmental biology, Cross-Sectional Studies, Neurology, Cohort, Observational study, Female, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

The management of impulse control disorders (ICDs) in Parkinson's disease (PD) relies on their early identification, allowing adjustment of antiparkinsonian treatment before these manifestations lead to major social, financial or legal consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) is an English-developed and -validated PD-specific rating scale constructed to support the rating of ICDs and related disorders and the assessment of changes in symptom severity over time, but it has not to date been validated in French.We conducted an observational, multicenter, cross-sectional study among a subset of patients (n = 280) from the Drug Interacting with Genes in PD (DIG-PD) cohort, aiming to assess psychometric properties of the French version of QUIP-RS: acceptability, internal consistency, factor analysis, reproductibility and hypotheses testing. In addition to this scale, the following measures were applied: MDS-Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination, Frontal Assessment Behavior, and Ardouin Scale of Behavior in Parkinson's Disease (ASBPD).Cronbach's alpha coefficient was 0.72 and ranged from 0.25 to 0.55. Regarding test-retest reliability and inter-rater reliability, the Lin concordance coefficient for items was higher than 0.58. The correlations between QUIP-RS and ASBPD were moderate to high except for dopaminergic addiction and hobbyism (r = 0.41 and 0.40 respectively, p 0.001). No clinically significant correlation was found between QUIP-RS total score (and items) and other scales.The French version of the QUIP-RS appears to be a valid, reliable, and precise instrument for the assessment of ICDs and related disorders in PD. REGISTRATION NUMBER: clinicaltrials.gov number NCT01564992.

Published
2019

9. Sleep and REM sleep behaviour disorder in Parkinson’s disease with impulse control disorder

Author

Franck Durif, Alessandro Cicolin, Michela Figorilli, Leonardo Lopiano, Maria Livia Fantini, Jean-Christophe Corvol, Eve Benchetrit, Monica Puligheddu, P. Beudin, Bruno Pereira, Maurizio Zibetti, Florence Cormier-Dequaire, Ana Marques, Isabelle Arnulf, Lucette Lacomblez, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Délégation à la Recherche Clinique et à l’Innovation, CHU Clermont-Ferrand, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Levodopa, Parkinson's disease, Movement disorders, Impulse control disorder, Polysomnography, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Video Recording, REM Sleep Behavior Disorder, REM sleep behavior disorder, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, medicine.diagnostic_test, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, Case-control study, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, medicine.disease, Antidepressive Agents, 3. Good health, Disruptive, Impulse Control, and Conduct Disorders, Psychiatry and Mental health, 030104 developmental biology, Case-Control Studies, Dopamine Agonists, Physical therapy, Female, Surgery, Neurology (clinical), Age of onset, medicine.symptom, Sleep, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract

IntroductionBecause the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson’s disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs.MethodsEighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case–control study. Forty patients (22 men; mean age: 62.6±9.7 years, Hoehn & Yahr: 2.1±0.6) with one or more current ICDs were age-matched and sex-matched with 40 patients with no history of ICDs (22 men, mean age: 64.9±7.8 years, Hoehn & Yahr: 2.2±0.6). They underwent a detailed sleep interview followed by a full-night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis included a clinical complaint of enacted dreams and/or documented behaviour during rapid eye movement (REM) sleep, with the presence of quantified REM sleep without atonia (RSWA).ResultsPatients with ICDs had a higher arousal index and higher RSWA than those without ICDs (51.9%±28.2%vs 32.2±27.1%, p=0.004). In addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was still associated with ICDs in a multivariate regression analysis including age of onset, PD duration and severity, treatment duration, levodopa-equivalent and dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI 1.3 to 18.5), p=0.02).ConclusionsThis large, controlled series of patients with PD with ICDs assessed by v-PSG confirms the association between ICDs and RBD. Increased surveillance of symptoms of ICDs should be recommended in patients with PD with RBD.

Published
2018

10. Differences in MDS-UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration

Author

Barbara C. Tilley, Eva Reiter, Klaus Seppi, Thomas Foltynie, Carlos Singer, Iciar Aviles-Olmos, Carmen Rodriguez-Blazquez, Michal Minár, Milan Grofik, Pille Taba, Vladimir Han, Henry Moore, Peter Valkovič, Alberto Bergareche-Yarza, Christopher G. Goetz, Eve Benchetrit, Matej Skorvanek, Graziella Mangone, Pablo Martinez-Martin, Anabel Chade, Anette Schrag, Werner Poewe, Norbert Kovács, Veronika Datieva, Amin Cervantes-Arriaga, Zuzana Gdovinova, Mario Alvarez-Sanchez, Nelida Garretto, Bernadette Pinter, Florence Cormier, Mari Muldmaa, Amelia Mendoza-Rodriguez, Juan Carlos Martínez-Castrillo, Oleg Levin, Jean-Christophe Corvol, Charline Benoit, Liis Kadastik-Eerme, David A. Gallagher, Tomoko Arakaki, Glenn T. Stebbins, Mayela Rodríguez-Violante, Monica M. Kurtis, Jing Huang, Karin Rallmann, Oscar S. Gershanik, Zsuzsanna Aschermann, and Christoph Mueller

Subjects
0301 basic medicine, Gerontology, medicine.medical_specialty, Parkinson's disease, Mds updrs, Disease duration, Hoehn and Yahr, Part iii, scale, 03 medical and health sciences, 0302 clinical medicine, Rating scale, Internal medicine, medicine, Stage (cooking), Motor assessment, Research Articles, Mean age, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), medicine.disease, nervous system diseases, 030104 developmental biology, Neurology, Neurology (clinical), disease duration, Psychology, 030217 neurology & neurosurgery
Abstract

BACKGROUND: The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. METHODS: For this cross‐sectional study, demographic data and MDS‐UPDRS scores were collected, including HY stage. Subscores on MDS‐UPDRS Parts I through IV were analyzed using 1‐way analyses of variance for each HY stage and in 5‐year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. RESULTS: The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0–5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS‐UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5‐year increments of disease duration, MDS‐UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. CONCLUSIONS: MDS‐UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5‐year increments of disease duration in the first 15 years of the disease.

Published
2017

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