Author: "Florence Pasquier" / Topic: neurology (clinical) - Searchworks@Jio Institute Digital Library Search Results

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1. Corrigendum to 'Dissemination in time and space in presymptomatic granulin mutation carriers: A spatial chronnectome study' [Neurobiology of Aging Volume 108, December 2021, Pages 155–167]

Author: Enrico Premi, Marcello Giunta, Armin Iraji, Srinivas Rachakonda, VinceD. Calhoun, Stefano Gazzina, Alberto Benussi, Roberto Gasparotti, Silvana Archetti, Martina Bocchetta, Dave Cash, Emily Todd, Georgia Peakman, Rhian Convery, John C. van Swieten, Lize Jiskoot, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, JamesB. Rowe, Mario Masellis, Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Chris R. Butler, Isabel Santana, Alexander Gerhard, Isabelle Le Ber, Florence Pasquier, Simon Ducharme, Johannes Levin, Adrian Danek, Sandro Sorbi, Markus Otto, Jonathan D. Rohrer, and Barbara Borroni
Subjects: Aging, General Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Abstract: Refers to Enrico Premi, Marcello Giunta, Armin Iraji, Srinivas Rachakonda, Vince D. Calhoun, Stefano Gazzina, Alberto Benussi, Roberto Gasparotti, Silvana Archetti, Martina Bocchetta, Dave Cash, Emily Todd, Georgia Peakman, Rhian Convery, John C. van Swieten, Lize Jiskoot, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, James B. Rowe, Mario Masellis, Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Chris R. Butler, Isabel Santana, Alexander Gerhard, Isabelle Le Ber, Florence Pasquier, Simon Ducharme, Johannes Levin, Adrian Danek, Sandro Sorbi, Markus Otto, Jonathan D. Rohrer, Barbara Borroni Dissemination in time and space in presymptomatic granulin mutation carriers: a GENFI spatial chronnectome study. Neurobiology of Aging, Volume 108, December 2021, Pages 155-167 DOI of original article: 10.1016/j.neurobiolaging.2021.09.001. © 2022 Elsevier Inc. The authors regret that the GENFI authors were listed at the end of the article in the Appendix. The GENFI authors are also part of co-authors. The updated author list is below. The authors would like to apologise for any inconvenience caused.
Published: 2022

2. Projet COG-AUDIO : évaluation des troubles de la compréhension de la parole dans le bruit au centre mémoire ressources recherche (CMRR) du CHU de Lille

Author: Pascaline Cassagnaud, Agnès Deneve, Nathan Zielinski, Christophe Vincent, Christian Renard, Florence Pasquier, Christine Moroni, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 (MBLC - ADDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
Subjects: [SCCO]Cognitive science, Neurology, Neurology (clinical)
Abstract: National audience; IntroductionLa presbyacousie comme les maladies neurodégénératives apparaissent insidieusement avec l’âge. Enjeu majeur de santé publique, elles sont néanmoins sous diagnostiquées car la présence de l’une entrave l’objectivation de l’autre.ObjectifsIntégrer lors du bilan cognitif en hôpital de jour en centre mémoire un dépistage des troubles de la compréhension de la parole dans le bruit.MéthodesCent vingt-deux participants, dont 70 femmes, d’âge moyen 72,9 (60–87 ans) ont réalisé trois épreuves : questionnaire Hearing Handicap Inventory for Elderly-Screening (HHIES) mesure la gêne auditive ; test de compréhension de la parole dans le bruit (dispositif ambulatoire – Vocal Rapide dans le Bruit, VRB Leclercq et al., 2018) et échelle cognitive de Mattis. Des analyses corrélationnelles entre l’âge, le résultat du VRB, le score HHIE-S et à la Mattis ont été menées.RésultatsLes corrélations objectivent une association entre les capacités de compréhension de la parole dans le bruit et l’âge (r = 0,324, p < 0,001), la gêne auditive (r = 0,249, p = 0,006) et les troubles cognitifs globaux (r = −0,502, p < 0,001).DiscussionCes résultats confortent le lien établi entre l’âge et les capacités de compréhension de la parole dans le bruit. Ils objectivent un lien entre la plainte auditive et les capacités de compréhension de la parole dans le bruit et révèlent que ces capacités sont amoindries chez les personnes ayant des troubles cognitifs objectivés à l’échelle de la Mattis.ConclusionLe dépistage précoce d’un déficit auditif lors d’évaluations cognitives est indispensable puisque la surdité est le principal facteur modifiable de la démence.
Published: 2023

3. The Benson Complex Figure Test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: A GENFI study

Author: Lize C. Jiskoot, Lucy L. Russell, Georgia Peakman, Rhian S. Convery, Caroline V. Greaves, Martina Bocchetta, Jackie M. Poos, Harro Seelaar, Lucia A.A. Giannini, John C. van Swieten, Rick van Minkelen, Yolande A.L. Pijnenburg, James B. Rowe, Barbara Borroni, Daniela Galimberti, Mario Masellis, Carmela Tartaglia, Elizabeth Finger, Chris R. Butler, Caroline Graff, Robert Laforce, Raquel Sanchez-Valle, Alexandre de Mendonça, Fermin Moreno, Matthis Synofzik, Rik Vandenberghe, Simon Ducharme, Isabelle le Ber, Johannes Levin, Markus Otto, Florence Pasquier, Isabel Santana, David M. Cash, David Thomas, Jonathan D. Rohrer, Neurology, Amsterdam Neuroscience - Neurodegeneration, Repositório da Universidade de Lisboa, and Clinical Genetics
Subjects: cognition, marker, neuropsychology, Presymptomatic, Marker, frontotemporal dementia, presymptomatic, Cognition, Neurology, Genetic, Neuropsychology, Frontotemporal dementia, Neurology (clinical), genetic
Abstract: © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/), Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates. Method: We included cross-sectional data from 332 presymptomatic and 136 symptomatic mutation carriers (GRN, MAPT or C9orf72 mutations), and 290 controls in the GENFI consortium. We examined gene-specific differences between mutation carriers (stratified by CDR® NACC-FTLD score) and controls using Quade's / Pearson Χ2 tests. We investigated associations with neuropsychological test scores and grey matter volume using partial correlations and multiple regression models respectively. Results: No significant differences were found between groups at CDR® NACC-FTLD 0-0.5. Symptomatic GRN and C9orf72 mutation carriers had lower Copy scores at CDR® NACC-FTLD ≥2. All three groups had lower Recall scores at CDR® NACC-FTLD ≥2, with MAPT mutation carriers starting at CDR® NACC-FTLD ≥1. All three groups had lower Recognition scores at CDR® NACC FTLD ≥2. Performance correlated with tests for visuoconstruction, memory, and executive function. Copy scores correlated with frontal-subcortical grey matter atrophy, while Recall scores correlated with temporal lobe atrophy. Conclusions: In the symptomatic stage, the BCFT identifies differential mechanisms of cognitive impairment depending on the genetic mutation, corroborated by gene-specific cognitive and neuroimaging correlates. Our findings suggest that impaired performance on the BCFT occurs relatively late in the genetic FTD disease process. Therefore its potential as cognitive biomarker for upcoming clinical trials in presymptomatic to early-stage FTD is most likely limited., The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (2019–02248), the Dioraphte Foundation [grant numbers 09–02-00], the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) (grant HCMI 056–13-018), ZonMw Memorabel (Deltaplan Dementie; project numbers 733050103 and 733050813), JPND PreFrontAls Consortium (project number 733051042) and Instituto de Salud Carlos III, Spain, and FEDER funds (grant number 20/00448). JBR is supported by the Wellcome Trust (103838), Medical Research Council (SUAG092 G116768) and the NIHR Cambridge Biomedical Research Centre (BRC-1215 − 20014: the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). JMP is supported by a fellowship award from Alzheimer Nederland (WE.15–2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1).
Published: 2023

4. Dissemination in time and space in presymptomatic granulin mutation carriers: a GENFI spatial chronnectome study

Author: Sandro Sorbi, Vince D. Calhoun, James B. Rowe, Isabelle Le Ber, Matthis Synofzik, Roberto Gasparotti, Martina Bocchetta, Enrico Premi, Dave Cash, Alexandre de Mendonça, Armin Iraji, Johannes Levin, Stefano Gazzina, A. Danek, Lize C. Jiskoot, Marcello Giunta, Alexander Gerhard, Markus Otto, Raquel Sánchez-Valle, Emily Todd, Genetic Frontotemporal dementia Initiative, Isabel Santana, Silvana Archetti, Rhian S Convery, Robert Laforce, Srinivas Rachakonda, Florence Pasquier, Fermin Moreno, John C. van Swieten, Georgia Peakman, Elizabeth Finger, Jonathan D. Rohrer, Christopher C Butler, Daniela Galimberti, Alberto Benussi, Carmela Tartaglia, Rik Vandenberghe, Caroline Graff, Mario Masellis, Fabrizio Tagliavini, Barbara Borroni, Simon Ducharme, Genetic Frontotemporal dementia Initiative (GENFI), Neurology, and Clinical Genetics
Subjects: Adult, Male, resting-state functional MRI, Heterozygote, Aging, Time Factors, Dissemination in time, Spatial Behavior, spatial chronnectome, Granulin, Biology, Research initiative, frontotemporal dementia, Executive Function, dynamic functional network connectivity, Frontotemporal Dementia, GRN mutation, medicine, Humans, Default mode network, Granulins, General Neuroscience, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Asymptomatic Diseases, Mutation, Mutation (genetic algorithm), Female, Neurology (clinical), Geriatrics and Gerontology, Neuroscience, Insula, Language network, Developmental Biology, Frontotemporal dementia
Abstract: The presymptomatic brain changes of granulin (GRN) disease, preceding by years frontotemporal dementia, has not been fully characterized. New approaches focus on the spatial chronnectome can capture both spatial network configurations and their dynamic changes over time. To investigate the spatial dynamics in 141 presymptomatic GRN mutation carriers and 282 noncarriers from the Genetic Frontotemporal dementia research Initiative cohort. We considered time-varying patterns of the default mode network, the language network, and the salience network, each summarized into 4 distinct recurring spatial configurations. Dwell time (DT) (the time each individual spends in each spatial state of each network), fractional occupacy (FO) (the total percentage of time spent by each individual in a state of a specific network) and total transition number (the total number of transitions performed by each individual in a specifict state) were considered. Correlations between DT, FO, and transition number and estimated years from expected symptom onset (EYO) and clinical performances were assessed. Presymptomatic GRN mutation carriers spent significantly more time in those spatial states characterised by greater activation of the insula and the parietal cortices, as compared to noncarriers (p < 0.05, FDR-corrected). A significant correlation between DT and FO of these spatial states and EYO was found, the longer the time spent in the spatial states, the closer the EYO. DT and FO significantly correlated with performances at tests tapping processing speed, with worse scores associated with increased spatial states’ DT. Our results demonstrated that presymptomatic GRN disease presents a complex dynamic reorganization of brain connectivity. Change in both the spatial and temporal aspects of brain network connectivity could provide a unique glimpse into brain function and potentially allowing a more sophisticated evaluation of the earliest disease changes and the understanding of possible mechanisms in GRN disease.
Published: 2021

5. Protective association of HLA‐DRB1 *04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences

Author: Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris E Jansen, Eric Yu, Aude Nicolas, Itziar de Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier‐Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D. Talyansky, Selina Marie Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Álvarez‐Martínez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo García‐Ribas, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Ling, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Shumpei Niida, Børge G. Nordestgaard, Goran Papenberg, Janne M. Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Eng‐King Tan, Thomas Tegos, Charlotte E. Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans R.J. Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Henrik Zetterberg, Kaj Blennow, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole Andreassen, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Ruth Frikke‐Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje M. van der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan‐Or, Jean‐Charles Lambert, Michael D Greicius, and Emmanuel Mignot
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

6. A multimodal, longitudinal study of cognitive heterogeneity in early‐onset Alzheimer's disease

Author: Florence Pasquier, Grégory Kuchcinski, Stéphanie Bombois, Xavier Delbeuck, Cécile Bordier, Renaud Lopes, Adeline Rollin-Sillaire, Emilie Skrobala, and Marianne Pollet
Subjects: Apolipoprotein E, Pediatrics, medicine.medical_specialty, Longitudinal study, medicine.diagnostic_test, business.industry, Neuroimaging, Cognition, Neuropsychological test, Disease, Neuropsychological Tests, medicine.disease, Neurology, Alzheimer Disease, Cohort, medicine, Humans, Early-onset Alzheimer's disease, Longitudinal Studies, Neurology (clinical), business
Abstract: BACKGROUND AND PURPOSE Alzheimer's disease (AD) is a heterogeneous pathology. Young patients with AD are particularly likely to have an atypical presentation. The objectives of the present cluster analysis were to determine whether patients with early-onset AD (EOAD) had several distinct cognitive profiles and to compare the resulting clusters with regard to clinical, neuroimaging, and laboratory characteristics. METHODS We collected cognitive, behavioural, functional, neuroimaging, and laboratory data on 72 patients meeting the criteria for probable mild EOAD. The patients were first classified into clinical phenotype groups by a multidisciplinary board of clinicians. The patients' cognitive and functional decline was monitored for 24 months. A k-means clustering analysis was then used to determine clusters on the basis of the patients' neuropsychological test results. RESULTS Two distinct clusters were identified: the patients in the first cluster (C1, n = 38) had a predominant memory impairment, whereas patients in the second (C2, n = 34) did not. Dyslipidaemia and the presence of ɛ4 apolipoprotein E allele were more frequent in C1, whereas the cognitive and functional decline was faster in the patients in C2. Moreover, posterior brain abnormalities were more severe in patients in C2 than in patients in C1. CONCLUSIONS By applying a k-means clustering analysis, we identified two clusters of patients in an EOAD cohort. The clusters differed with regard to certain clinical, imaging, and laboratory characteristics. This clustering procedure might be of value for managing patients with EOAD in general and for identifying those at risk of more rapid decline in particular.
Published: 2021

7. Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

Author: Frederic Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro de Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Sandrine Harston, Anne Botzung, Timothée Albasser, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Stéphane Kremer, Olivier Bousiges, Marc Verny, Candice Muller, Nathalie Philippi, Geneviève Chene, Benjamin Cretin, Jean-François Mangin, and Carole Dufouil
Subjects: Cohort Studies, Lewy Body Disease, Neurology, Alzheimer Disease, Photophobia, Cognitive Neuroscience, Humans, Prodromal Symptoms, Cognitive Dysfunction, Neurology (clinical)
Abstract: Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov, NCT01926249
Published: 2022

8. Biomarqueurs du liquide cérébrospinal

Author: Melanie Leroy, Florence Pasquier, S. Schraen, Thibaud Lebouvier, L. Vaudran, Yaohua Chen, and Vincent Deramecourt
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030212 general & internal medicine, Neurology (clinical), 030217 neurology & neurosurgery
Abstract: Resume Le dosage des biomarqueurs du liquide cerebrospinal (LCS) a integre depuis maintenant plusieurs annees la demarche diagnostique en cas de suspicion de maladie d’Alzheimer (MA). En France, ou l’imagerie moleculaire n’est pas accessible en soin courant, ils sont le seul outil disponible pour poser un diagnostic biologique de MA selon les criteres de 2018. La combinaison de Aβ1-42 et Aβ1-40 predit avec une excellente sensibilite et specificite la presente d’une pathologie amyloide (A), tandis que P-Tau et T-tau sont des biomarqueurs de la taupathie associee a la MA (T), T-tau ayant une moindre specificite que P-tau. L’association de ces quatre biomarqueurs peut differencier une MA d’une autre maladie neurodegenerative et poser un diagnostic de MA des le stade prodromal ou preclinique. Les biomarqueurs ont toutefois des limites qui tiennent d’abord a la variabilite du dosage, liee a des facteurs pre-analytiques et analytiques. L’harmonisation des procedures, l’automatisation et les efforts encore en cours de standardisation contribuent a reduire les sources de variabilite. Leur interpretation est souvent difficile, liee notamment aux profils ambigus (A+T- ou A-T+) et a la frequence des associations pathologiques, notamment chez le sujet tres âge. Ils conservent neanmoins a tout âge une excellente valeur predictive negative a tout âge. L’arrivee annoncee des biomarqueurs sanguins releguera peut-etre les biomarqueurs du LCS au second plan. Ils resteront neanmoins pour les annees a venir un gold standard biologique.
Published: 2021

9. Étude rétrospective d’une population de patients atteints de maladie d’Alzheimer sans altération du métabolisme cérébral en TEP au 18F-FDG

Author: Diane Villemonte de la Clergerie, Florent Hives, Soufiane Djelad, Florence Pasquier, Thibaud Lebouvier, and Franck Semah
Subjects: Neurology, Neurology (clinical)
Published: 2023

10. Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up

Author: Dario, Saracino, Leila, Sellami, Hugo, Boniface, Marion, Houot, Mélanie, Pélégrini-Issac, Aurélie, Funkiewiez, Daisy, Rinaldi, Maxime, Locatelli, Carole, Azuar, Valérie, Causse-Lemercier, Alice, Jaillard, Florence, Pasquier, Mathieu, Chastan, David, Wallon, Anne, Hitzel, Jeremie, Pariente, Amandine, Pallardy, Claire, Boutoleau-Bretonnière, Eric, Guedj, Mira, Didic, Raffaella, Migliaccio, Aurélie, Kas, Marie-Odile, Habert, Isabelle, Le Ber, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background and ObjectivesGRNvariants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)–PET in identifying metabolic changes in presymptomaticGRNcarriers (PS-GRN+) and to trace their longitudinal progression.MethodsParticipants were longitudinally evaluated over 5 years in a prospective cohort study focused onGRNdisease (Predict-PGRN). They underwent cognitive/behavioral assessment, plasma neurofilament measurement, brain MRI, and FDG-PET. Voxel-wise comparisons of structural and metabolic imaging data between 2 groups were performed for each time point. Longitudinal PET changes were evaluated with voxel-wise comparisons and the metabolic percent annual changes method. The association of regional brain metabolism with plasma neurofilament and cognitive changes was analyzed.ResultsAmong the 80 individuals enrolled in the study, 58 (27 PS-GRN+ and 31 noncarriers) were included in the analyses. Cross-sectional comparisons between PS-GRN+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (p< 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (−1.37%) was higher than that in controls (−0.21%,p= 0.004). Lower glucose uptake was associated with higher neurofilament increase (p= 0.003) and lower frontal cognitive scores (p= 0.014) in PS-GRN+.DiscussionThis study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinicalGRNdisease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.
Published: 2022

11. Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders

Author: Florence Pasquier, Mathieu Vandenbulcke, John R. Hodges, Mario Masellis, Alan J. Lerner, Chiadi U. Onyike, Yolande A.L. Pijnenburg, Wendy Kelso, Dennis Velakoulis, Fiona Kumfor, Carole Azuar, Robert Laforce, Peter Pressman, John C. van Swieten, Ratnavalli Ellajosyula, Jan Van den Stock, Calvin Trieu, Dhamidhu Eratne, Leonardo Cruz de Souza, Daniela Galimberti, Everard G. B. Vijverberg, Bradley F. Boeve, Maria Landqvist Waldö, Howard J. Rosen, Olivier Piguet, Rik Vandenberghe, Alexander Santillo, Annemiek Dols, Flora Gossink, Harro Seelaar, Ramon Landin-Romero, Mario F. Mendez, Elio Scarpini, Caroline Dallaire-Théroux, David C. Perry, Janine Diehl-Schmid, Simon Ducharme, Edward D. Huey, Michael Hornberger, Paulo Caramelli, Emma Devenney, Manabu Ikeda, Sandra Baez, Isabelle Le Ber, Richard Levy, APH - Mental Health, Amsterdam Neuroscience - Neurodegeneration, Neurology, and Psychiatry
Subjects: Male, Delayed Diagnosis, Neuropsychological Tests, Neurodegenerative, frontotemporal dementia, Medical and Health Sciences, Diagnosis, differential diagnosis, Neuropsychological assessment, guidelines, Review Articles, Neurologic Examination, screening and diagnosis, medicine.diagnostic_test, Psychiatric assessment, Mental Disorders, Corrigenda, Magnetic Resonance Imaging, psychiatry, Frontotemporal Dementia (FTD), Detection, Mental Health, Schizophrenia, Frontotemporal Dementia, Neurological, Major depressive disorder, Female, Frontotemporal dementia, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Neuroimaging, Diagnosis, Differential, Fluorodeoxyglucose F18, Clinical Research, Behavioral and Social Science, medicine, Acquired Cognitive Impairment, Dementia, Humans, Medical history, Bipolar disorder, Psychiatry, Neurology & Neurosurgery, business.industry, Prevention, Psychology and Cognitive Sciences, Neurosciences, biomarkers, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Positron-Emission Tomography, Differential, Neurology (clinical), business
Abstract: The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5–6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible/probable bvFTD cases or suspected cases with strong psychiatric features.
Published: 2020

12. What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders?

Author: Anders Wallin, Suvarna Alladi, Sandra E Black, Christopher Chen, Steven M Greenberg, Deborah Gustafson, Jeremy D Isaacs, Hanna Jokinen, Raj Kalaria, Vincent Mok, Leonardo Pantoni, Florence Pasquier, Gustavo C Roman, Gary A. Rosenberg, Reinhold Schmidt, Eric E Smith, and Atticus H Hainsworth
Subjects: Behavioral Neuroscience, Neurology, Cognitive Neuroscience, Neurology (clinical), Biological Psychiatry
Abstract: •Controversial registration of aducanumab for Alzheimer's Disease•Aducanumab is the subject of post-licensing observational studies aiming to follow the effects of the drug•Given the high prevalence of cerebrovascular pathology it is important that these studies do not ignore vascular cognitive disorders•The studies may give detailed phenotyping data that may lead to knowledge of targets for treatments of patients with vascular cognitive disorders.
Published: 2022

13. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE‐ε4

Author: Yann Le Guen, Michael E Belloy, Benjamin Grenier‐Boley, Itziar de Rojas, Atahualpa Castillo, Iris E Jansen, Aude Nicolas, Céline Bellenguez, Carolina Dalmasso, Fahri Küçükali, Sarah J Eger, Victoria Álvarez‐Martínez, Beatrice Arosio, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimón, Delphine Daian, Antonio Daniele, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emrah Duzel, Daniela Galimberti, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Timo Grimmer, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Deckert Jurgen, Teemu Kuulasmaa, Aad van der Lugt, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Inez H.G.B. Ramakers, Katrine Laura Rasmussen, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Hilkka Soininen, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Thomas Tegos, Jesper Qvist Thomassen, Lucio Tremolizzo, Frans R.J. Verhey, Martin Vyhnalek, Jens Wiltfang, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M. van der Flier, Alfredo Ramirez, Ole Andreassen, Ruth Frikke‐Schmidt, Julie Williams, Agustin Ruiz, Jean‐Charles Lambert, and Michael D Greicius
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

14. A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers

Author: Yolande A.L. Pijnenburg, Alessandro Padovani, Lieke H.H. Meeter, Rita Guerreiro, Mathieu Vandenbulcke, Rose Bruffaerts, Sonja Schönecker, Sofia Bergström, Florence Pasquier, Mikel Tainta, Beatriz Santiago, Roberto Gasparotti, Maria Rosário Almeida, Núria Bargalló, Abbe Ullgren, Martina Bocchetta, James B. Rowe, Pietro Tiraboschi, Robart Bartha, Rachelle Shafei, Benjamin Bender, Anna Månberg, Enrico Premi, Sergi Borrego-Écija, Sandro Sorbi, Christopher C Butler, Rick van Minkelen, Alberto Benussi, Marta Cañada, Carlo Wilke, Christin Andersson, Caroline Graff, Isabel Santana, Elisa Semler, Valentina Bessi, Miren Zulaica, Benedetta Nacmias, Tobias Langheinrich, Christen Shoesmith, Philip Van Damme, Camilla Ferrari, Martin Rosser, Pedro Rosa-Neto, Alexandre de Mendonça, Jennifer M. Nicholas, Catharina Prix, Sebastien Ourselin, Michele Veldsman, Jessica L. Panman, Håkan Thonberg, Jennie Olofsson, Paul M. Thompson, Ana Gorostidi, Andrea Arighi, Raquel Sánchez-Valle, Anna Antonell, Vesna Jelic, Ana Verdelho, Sara Mitchell, Janne M. Papma, Alina Díez, Giuliano Binetti, Rhian S Convery, Silvana Archetti, Ekaterina Rogaeva, Michela Pievani, C. Ferreira, Hans-Otto Karnath, Veronica Redaelli, Giuseppe Di Fede, Giovanni B. Frisoni, Carolina Maruta, Giacomina Rossi, Jaume Olives, Simon Ducharme, Roberta Ghidoni, Alexander Gerhard, Ron Keren, Johannes Levin, Sandra V. Loosli, Jose Bras, Isabelle Le Ber, Emily Todd, Robert Laforce, Sónia Afonso, Matthis Synofzik, Alazne Gabilondo, Elizabeth Finger, Thomas E. Cope, Paola Caroppo, Jorge Villanua, Diana Duro, Georgia Peakman, Giorgio G. Fumagalli, Serge Gauthier, Mario Masellis, Markus Otto, Caroline V. Greaves, Carolyn Timberlake, Harro Seelaar, Ione O.C. Woollacott, Sara Prioni, Jason D. Warren, Cristina Polito, Miguel Tábuas-Pereira, David F. Tang-Wai, Carmela Tartaglia, Linn Öijerstedt, Luisa Benussi, Barbara Borroni, Ricardo Taipa, Albert Lladó, Mircea Balasa, Rosa Rademakers, Lize C. Jiskoot, Miguel Castelo-Branco, Julia Remnestål, Fabrizio Tagliavini, Giorgio Giaccone, Maria João Leitão, Henrik Zetterberg, Valentina Cantoni, Daniela Galimberti, Sarah Anderl-Straub, Simon Mead, Myriam Barandiaran, Adrian Danek, Timothy Rittman, Chiara Fenoglio, Katrina M. Moore, David M. Cash, Rik Vandenberghe, Peter Nilsson, Elisabeth Wlasich, John C. van Swieten, Morris Freedman, Sandra E. Black, Carolin Heller, Stefano Gazzina, Gabriel Miltenberger, Fermin Moreno, Nick C. Fox, David L. Thomas, Jonathan D. Rohrer, Begoña Indakoetxea, Tobias Hoegen, Gemma Lombardi, Elio Scarpini, Bergström, Sofia [0000-0003-2910-4754], Apollo - University of Cambridge Repository, Neurology, Amsterdam Neuroscience - Neurodegeneration, Genetic Frontotemporal Dementia Initiative (GENFI), Jiskoot, Lize (Beitragende*r), Rowe, James B. (Beitragende*r), de Mendonça, Alexandre (Beitragende*r), Tagliavini, Fabrizio (Beitragende*r), Santana, Isabel (Beitragende*r), Le Ber, Isabelle (Beitragende*r), Levin, Johannes (Beitragende*r), Danek, Adrian (Beitragende*r), Otto, Markus (Beitragende*r), Frisoni, Giovanni (Beitragende*r), Ghidoni, Roberta (Beitragende*r), Sorbi, Sandro (Beitragende*r), Pasquier, Florence (Beitragende*r), Jelic, Vesna (Beitragende*r), Andersson, Christin (Beitragende*r), Afonso, Sónia (Beitragende*r), Almeida, Maria Rosario (Beitragende*r), Anderl-Straub, Sarah (Beitragende*r), Antonell, Anna (Beitragende*r), Archetti, Silvana (Beitragende*r), Arighi, Andrea (Beitragende*r), Balasa, Mircea (Beitragende*r), Barandiaran, Myriam (Beitragende*r), Bargalló, Nuria (Beitragende*r), Bartha, Robart (Beitragende*r), Bender, Benjamin (Beitragende*r), Benussi, Alberto (Beitragende*r), Benussi, Luisa (Beitragende*r), Bessi, Valentina (Beitragende*r), Binetti, Giuliano (Beitragende*r), Black, Sandra (Beitragende*r), Bocchetta, Martina (Beitragende*r), Borrego-Ecija, Sergi (Beitragende*r), Bras, Jose (Beitragende*r), Bruffaerts, Rose (Beitragende*r), Cañada, Marta (Beitragende*r), Cantoni, Valentina (Beitragende*r), Caroppo, Paola (Beitragende*r), Cash, David (Beitragende*r), Castelo-Branco, Miguel (Beitragende*r), Convery, Rhian (Beitragende*r), Cope, Thomas (Beitragende*r), Di Fede, Giuseppe (Beitragende*r), Díez, Alina (Beitragende*r), Duro, Diana (Beitragende*r), Fenoglio, Chiara (Beitragende*r), Ferrari, Camilla (Beitragende*r), Ferreira, Catarina B. (Beitragende*r), Fox, Nick (Beitragende*r), Freedman, Morris (Beitragende*r), Fumagalli, Giorgio (Beitragende*r), Gabilondo, Alazne (Beitragende*r), Gasparotti, Roberto (Beitragende*r), Gauthier, Serge (Beitragende*r), Gazzina, Stefano (Beitragende*r), Giaccone, Giorgio (Beitragende*r), Gorostidi, Ana (Beitragende*r), Greaves, Caroline (Beitragende*r), Guerreiro, Rita (Beitragende*r), Heller, Carolin (Beitragende*r), Hoegen, Tobias (Beitragende*r), Indakoetxea, Begoña (Beitragende*r), Karnath, Hans-Otto (Beitragende*r), Keren, Ron (Beitragende*r), Langheinrich, Tobias (Beitragende*r), Leitão, Maria João (Beitragende*r), Lladó, Albert (Beitragende*r), Lombardi, Gemma (Beitragende*r), Loosli, Sandra (Beitragende*r), Maruta, Carolina (Beitragende*r), Mead, Simon (Beitragende*r), Meeter, Lieke (Beitragende*r), Miltenberger, Gabriel (Beitragende*r), van Minkelen, Rick (Beitragende*r), Mitchell, Sara (Beitragende*r), Moore, Katrina (Beitragende*r), Nacmias, Benedetta (Beitragende*r), Nicholas, Jennifer (Beitragende*r), Olives, Jaume (Beitragende*r), Ourselin, Sebastien (Beitragende*r), Padovani, Alessandro (Beitragende*r), Panman, Jessica (Beitragende*r), Papma, Janne M. (Beitragende*r), Peakman, Georgia (Beitragende*r), Pievani, Michela (Beitragende*r), Pijnenburg, Yolande (Beitragende*r), Polito, Cristina (Beitragende*r), Premi, Enrico (Beitragende*r), Prioni, Sara (Beitragende*r), Prix, Catharina (Beitragende*r), Rademakers, Rosa (Beitragende*r), Redaelli, Veronica (Beitragende*r), Rittman, Tim (Beitragende*r), Rogaeva, Ekaterina (Beitragende*r), Rosa-Neto, Pedro (Beitragende*r), Rossi, Giacomina (Beitragende*r), Rosser, Martin (Beitragende*r), Santiago, Beatriz (Beitragende*r), Scarpini, Elio (Beitragende*r), Schönecker, Sonja (Beitragende*r), Semler, Elisa (Beitragende*r), Shafei, Rachelle (Beitragende*r), Shoesmith, Christen (Beitragende*r), Tábuas-Pereira, Miguel (Beitragende*r), Tainta, Mikel (Beitragende*r), Taipa, Ricardo (Beitragende*r), Tang-Wai, David (Beitragende*r), Thomas, David L. (Beitragende*r), Thompson, Paul (Beitragende*r), Thonberg, Håkan (Beitragende*r), Timberlake, Carolyn (Beitragende*r), Tiraboschi, Pietro (Beitragende*r), Todd, Emily (Beitragende*r), Van Damme, Philip (Beitragende*r), Vandenbulcke, Mathieu (Beitragende*r), Veldsman, Michele (Beitragende*r), Verdelho, Ana (Beitragende*r), Villanua, Jorge (Beitragende*r), Warren, Jason (Beitragende*r), Wilke, Carlo (Beitragende*r), Woollacott, Ione (Beitragende*r), Wlasich, Elisabeth (Beitragende*r), Zetterberg, Henrik (Beitragende*r), and Zulaica, Miren (Beitragende*r)
Subjects: medicine.medical_specialty, Neurology, NEFM, Medizin, genetics [Mutation], LASSO, Biology, Aquaporin 4 (AQP4), Neurosecretory protein VGF (VGF), DISEASE, genetics [Progranulins], Cellular and Molecular Neuroscience, Progranulins, CEREBROSPINAL-FLUID, C9orf72, ddc:570, medicine, CRITERIA, Humans, Neuronal pentraxin 2 (NPTX2), RC346-429, genetics [Frontotemporal Dementia], Molecular Biology, Pathological, Genetics, Science & Technology, Neurosciences, RC952-954.6, Brain, Neurofilament medium polypeptide (NEFM), medicine.disease, Molecular medicine, Cerebrospinal fluid, Aquaporin 4, Geriatrics, Suspension bead array, Frontotemporal Dementia, Mutation, Mutation (genetic algorithm), Neurosciences & Neurology, Neurology. Diseases of the nervous system, Neurology (clinical), Life Sciences & Biomedicine, Random forest, Biomarkers, Research Article, Frontotemporal dementia
Abstract: Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Supplementary Information: Additional file 1 of A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study; Additional file 2 of A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study; both files are available online at https://doi.org/10.1186/s13024-021-00499-4 Copyright © The Author(s) 2021. Background: A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods: A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results: When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion: In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD. This study has received support from the Swedish FTD initiative funded by the Schörling Family Foundation. This work was also funded by KTH Center for Applied Precision Medicine (KCAP) funded by the Erling-Persson Family Foundation, grants from Vetenskapsrådet Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, Swedish Alzheimer Foundation, Swedish Brain Foundation, Åhlén foundation, Demensfonden, Stohnes foundation, Gamla Tjänarinnor and Stockholm County Council ALF. Furthermore, support was received by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (2019-02248), the Dioraphte Foundation [grant numbers 09-02-00]; the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO) (grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie), (project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. M.S. was supported by the JPND grant “GENFI-prox” (by DLR/BMBF to M. S, joint with JDR., J.vS., M.O., B.B. and C.G.). Open Access funding provided by Royal Institute of Technology.
Published: 2021

15. Telemedicine in French memory clinics during Covid‐19 crisis

Author: Alexandre Morin, Thibault Pressat‐Laffouilhere, Marie Sarazin, Julien Lagarde, Carole Roue‐Jagot, Claire Paquet, Emmanuel Cognat, Julien Dumurgier, Florence Pasquier, Thibaud Lebouvier, Mathieu Ceccaldi, Olivier Godefroy, Olivier Martinaud, Julien Grosjean, Aline Zarea, David Maltête, and David Wallon
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021

16. Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Author: Julien, Dumurgier, Séverine, Sabia, Henrik, Zetterberg, Charlotte, Teunissen, Bernard, Hanseeuw, Adelina, Orellana, Susanna, Schraen, Audrey, Gabelle, Mercè, Boada, Thibaud, Lebouvier, Eline A J, Willemse, Emmanuel, Cognat, Agustin, Ruiz, Claire, Hourregue, Matthieu, Lilamand, Elodie, Bouaziz-Amar, Jean-Louis, Laplanche, Sylvain, Lehmann, Florence, Pasquier, Philip, Scheltens, Kaj, Blennow, Archana, Singh-Manoux, Claire, Paquet, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology
Subjects: Male, Amyloid beta-Peptides, Alzheimer Disease, Positron-Emission Tomography, Humans, Female, tau Proteins, Neurology (clinical), Biomarkers, Peptide Fragments, Aged
Abstract: Background and ObjectivesTo elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.MethodsLow and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients.ResultsA total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%.DiscussionThe proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
Published: 2021

17. SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration

Author: Barbier, Mathieu, Camuzat, Agnès, Hachimi, Khalid El, Guegan, Justine, Rinaldi, Daisy, Lattante, Serena, Houot, Marion, Sánchez-Valle, Raquel, Sabatelli, Mario, Antonell, Anna, Molina-Porcel, Laura, Clot, Fabienne, Couratier, Philippe, van der Ende, Emma, van der Zee, Julie, Manzoni, Claudia, Camu, William, Cazeneuve, Cécile, Sellal, François, Didic, Mira, Golfier, Véronique, Pasquier, Florence, Duyckaerts, Charles, Rossi, Giacomina, Bruni, Amalia C, Alvarez, Victoria, Gómez-Tortosa, Estrella, de Mendonça, Alexandre, Graff, Caroline, Masellis, Mario, Nacmias, Benedetta, Oumoussa, Badreddine Mohand, Jornea, Ludmila, Forlani, Sylvie, Van Deerlin, Viviana, Rohrer, Jonathan D, Gelpi, Ellen, Rademakers, Rosa, Van Swieten, John, Le Guern, Eric, Van Broeckhoven, Christine, Ferrari, Raffaele, Génin, Emmanuelle, Brice, Alexis, Ber, Le, Isabelle Alexis Brice, Sophie, Auriacombe, Serge, Belliard, Anne, Bertrand, Anne, Bissery, Fre ́ de, ́ ric Blanc, Marie-Paule, Boncoeur, Ste, ́ phanie Bombois, Claire Boutoleau-Bretonnie` re, Agne`, s Camuzat, Mathieu, Ceccaldi, Marie, Chupin, Philippe, Couratier, Olivier, Colliot, Vincent, Deramecourt, Mira, Didic, Bruno, Dubois, Charles, Duyckaerts, Fre ́ de, ́ rique Etcharry-Bouyx, Aure, ́ lie Guignebert-Funkiewiez, Maı ̈te, ́ Formaglio, ́ ronique Golfier, Ve, Marie-Odile, Habert, Didier, Hannequin, Lucette, Lacomblez, Julien, Lagarde, ́ raldine Lautrette, Ge, Isabelle Le Ber, Benjamin Le Toullec, Richard, Levy, Marie-Anne, Mackowiak, Bernard-Franc ̧ois Michel, Florence, Pasquier, Thibaud, Lebouvier, Carole Roue, ́ -Jagot, Christel Thauvin- Robinet, Catherine, Thomas-Anterion, Je ́ re, ́ mie Pariente, Franc ̧ois Salachas, Sabrina, Sayah, Franc ̧ois Sellal, Assi-Herve, ́ Oya, Daisy, Rinaldi, Adeline, Rollin-Sillaire, Martine, Vercelletto, David, Wallon, Armelle, Rametti-Lacroux, Raffaele, Ferrari, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Adaikalavan, Ramasamy, Kwok, John B. J., Carol Dobson- Stone, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Olivier, Piguet, Lauren, Bartley, Elizabeth, Thompson, Isabel Herna, ́ ndez, Agustı ́n Ruiz, Merce`, Boada, Barbara, Borroni, Alessandro, Padovani, Carlos, Cruchaga, Cairns, Nigel J., Luisa, Benussi, Giuliano, Binetti, Roberta, Ghidoni, Gianluigi, Forloni, Diego, Albani, Daniela, Galimberti, Chiara, Fenoglio, Maria, Serpente, Elio, Scarpini, ́ n, Jordi Clarimo, Alberto Lleo, ́, Rafael, Blesa, Maria Landqvist Waldo, ̈, Karin, Nilsson, Christer, Nilsson, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Jordan, Grafman, Morris, Christopher M., Johannes, Attems, Griffiths, Timothy D., Mckeith, Ian G., Thomas, Alan J., Pietro, Pietrini, Edward, Uey, Wassermann, Eric M., Atik, Baborie, Evelyn, Jaros, Tierney, Michael C., Pau, Pastor, Cristina, Razquin, Sara, Ortega-Cubero, Elena, Alonso, Robert, Perneczky, Janine, Diehl-Schmid, Panagiotis, Alexopoulos, Alexander, Kurz, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Ekaterina, Rogaeva, Peter St George-Hyslop, Giacomina, Rossi, Fabrizio, Tagliavini, Giorgio, Giaccone, Rowe, James B., Schlachetzki, Johannes C. M., James, Uphill, John, Collinge, Simon, Mead, Adrian, Danek, Van Deerlin, Vivianna M., Murray, Grossman, Trojanowski, John Q., Julie van der Zee, Christine Van Broeckhoven, Cappa, Stefano F., Isabelle, Leber, Alexis, Brice, Benedetta, Nacmias, Sandro, Sorbi, Silvia, Bagnoli, Irene, Piaceri, Nielsen, Jørgen E., Hjermind, Lena E., Matthias, Riemenschneider, Manuel, Mayhaus, Bernd, Ibach, Gilles, Gasparoni, Sabrina, Pichler, Wei, Gu, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Maria Grazia Spillantini, Morris, Huw R., Patrizia, Rizzu, Peter, Heutink, Snowden, Julie S., Sara, Rollinson, Anna, Richardson, Alexander, Gerhard, Bruni, Amalia C., Raffaele, Maletta, Francesca, Frangipane, Chiara, Cupidi, Livia, Bernardi, Maria, Anfossi, Maura, Gallo, Maria Elena Conidi, Nicoletta, Smirne, Rosa, Rademakers, Matt, Baker, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., David, Knopman, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Howard, Rosen, van Swieten, John C., Dopper, Elise G. P., Harro, Seelaar, Pijnenburg, Yolande A. L., Philip, Scheltens, Giancarlo, Logroscino, Rosa, Capozzo, Valeria, Novelli, Puca, Annibale A., Massimo, Franceschi, Alfredo, Postiglione, Graziella, Milan, Paolo, Sorrentino, Mark, Kristiansen, Huei-Hsin, Chiang, Caroline, Graff, Adeline, Rollin, Dimitrios, Kapogiannis, Luigi, Ferrucci, Stuart, Pickering-Brown, Singleton, Andrew B., John, Hardy, Parastoo, Momeni., Neurology, Amsterdam Neuroscience - Neurodegeneration, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Dupuytren [CHU Limoges], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Molecular Neurology (VIB-UAntwerp), University of Antwerp (UA), University College of London [London] (UCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Yves le Foll, 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), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Hospital Central de Asturias, Institute of Health Research of Principado de Asturias (ISPA), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Karolinska University Hospital [Stockholm], Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione Don Carlo Gnocchi, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), The French clinical and genetic Research network on FTLD/FTLD-ALS and PREVDEMALS, The International Frontotemporal Dementia Genomics Consortium, The European Early Onset Dementia (EU -EOD) Consortium, Brainbank Neuro-CEB Neuropathology Network, and Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS
Subjects: Adult, Male, TDP-43, C9orf72, SLITRK2, amyotrophic lateral sclerosis, frontotemporal dementia, Nerve Tissue Proteins, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Cohort Studies, Genes, X-Linked, 80 and over, Medicine, Dementia, Humans, Allele, Age of Onset, Polymorphism, Aged, Aged, 80 and over, biology, C9orf72 Protein, business.industry, Membrane Proteins, MESH: Frontotemporal Lobar Degeneration / epidemiology, Frontotemporal Lobar, Degeneration / genetics, Genes, X-Linked / genetics, Genome-Wide Association Study / methods, Frontotemporal lobar degeneration, Single Nucleotide, Middle Aged, X-Linked, medicine.disease, Amyotrophic lateral sclerosis, Minor allele frequency, Genes, Immunology, Synaptophysin, biology.protein, Female, MESH: Adult, C9orf72 Protein / genetics, Frontotemporal Lobar Degeneration / diagnosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Human medicine, Neurology (clinical), MESH: Humans, Membrane Proteins / genetics, Nerve Tissue Proteins / genetics, Polymorphism, Single Nucleotide / genetics, Age of onset, Frontotemporal Lobar Degeneration, business, Frontotemporal dementia, Genome-Wide Association Study
Abstract: The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.
Published: 2021

18. Profil d’atrophie de la substance grise et modifications longitudinales chez les porteurs d’expansion C9orf72 au stade présymptomatique

Author: Dario Saracino, Lorenzo Cipriano, Marion Houot, Philippe Couratier, David Wallon, Florence Pasquier, and Isabelle Le Ber
Subjects: Neurology, Neurology (clinical)
Published: 2022

19. Investigating the association between cancer and the risk of dementia: Results from the Memento cohort

Author: Mathieu Ceccaldi, Audrey Gabelle, Bruno Dubois, Carole Dufouil, David Wallon, Olivier Hanon, Armelle Gentric, Pierre Krolak-Salmon, Yannick Béjot, Geneviève Chêne, Olivier Godefroy, Jonviea D Chamberlain, Anaïs Rouanet, Florence Pasquier, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-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), 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), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Mémoire de Ressources et de Recherches (CMRR), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Bordeaux [Bordeaux], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, medicine.medical_specialty, media_common.quotation_subject, Neuropsychological Tests, illness-death model, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, illness‐death model, 0302 clinical medicine, Developmental Neuroscience, Internal medicine, Neoplasms, Epidemiology, medicine, Dementia, Humans, cancer, Cognitive Dysfunction, selection bias, 030212 general & internal medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mortality, Research Articles, media_common, Aged, Selection bias, business.industry, Health Policy, Hazard ratio, Cancer, Cognition, Alzheimer's disease, medicine.disease, Confidence interval, 3. Good health, Psychiatry and Mental health, Cohort, Female, epidemiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), France, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research Article, dementia
Abstract: International audience; IntroductionStudies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding.MethodsThis study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness‐death models (IDMs) were used to estimate transition‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry.ResultsThe analytical sample (N = 2258) excluded 65 individuals without follow‐up information. At the end of follow‐up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35‐0.97), with a corresponding E‐value of 2.84 (lower CI = 1.21).DiscussionThis study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.
Published: 2021

20. Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Nonamyloid Logopenic Variant

Author: Bruno Dubois, Audrey Gabelle, François Sellal, Jérémie Pariente, Marie Sarazin, Agnès Camuzat, Raffaella Migliaccio, Frédérique Etcharry-Bouyx, Amandine Geraudie, Sophie Ferrieux, Simona Bottani, Carole Roué-Jagot, Mira Didic, Florence Pasquier, Leila Sellami, Alexis Brice, Olivier Colliot, Fabienne Clot, Marc Teichmann, Didier Hannequin, Christel Thauvin-Robinet, Claire Boutoleau-Bretonnière, Julien Lagarde, Cinzia Coppola, David Wallon, Richard Levy, Marie Noguès-Lassiaille, Dario Saracino, Aurélie Funkiewiez, Maria Luisa Gorno-Tempini, Olivier Martinaud, Isabelle Le Ber, Marion Houot, Stéphane Epelbaum, Sophie Auriacombe, Alexandre Morin, Vincent Deramecourt, Ftd-Als, Philippe Couratier, Daisy Rinaldi, Saracino, Dario, Ferrieux, Sophie, Noguès-Lassiaille, Marie, Houot, Marion, Funkiewiez, Aurélie, Sellami, Leila, Deramecourt, Vincent, Pasquier, Florence, Couratier, Philippe, Pariente, Jérémie, Géraudie, Amandine, Epelbaum, Stéphane, Wallon, David, Hannequin, Didier, Martinaud, Olivier, Clot, Fabienne, Camuzat, Agnè, Bottani, Simona, Rinaldi, Daisy, Auriacombe, Sophie, Sarazin, Marie, Didic, Mira, Boutoleau-Bretonnière, Claire, Thauvin-Robinet, Christel, Lagarde, Julien, Roué-Jagot, Carole, Sellal, Françoi, Gabelle, Audrey, Etcharry-Bouyx, Frédérique, Morin, Alexandre, Coppola, Cinzia, Levy, Richard, Dubois, Bruno, Brice, Alexi, Colliot, Olivier, Luisa Gorno-Tempini, Maria, Teichmann, Marc, Migliaccio, Raffaella, Le Ber, Isabelle, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CHU Limoges, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), 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)-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)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Charles Foix [AP-HP], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), GHU AP-HP Centre Université de Paris, Hôpitaux Civils de Colmar, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), University of the Study of Campania Luigi Vanvitelli, University of California [San Francisco] (UC San Francisco), University of California (UC), The research leading to these results received funding from the Investissements davenir ANR-11-INBS-0011. This work was funded by the Programme Hospitalier de Recherche Clinique (PHRC) FTLD-exome (to ILB, promotion by Assistance Publique Hôpitaux de Paris), PHRC Predict-PGRN (to ILB, promotion by Assistance Publique Hôpitaux de Paris)., ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), Admin, Oskar, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, 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), CHU Toulouse [Toulouse], Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-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), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), University of California, 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE)
Subjects: Oncology, medicine.medical_specialty, Apraxia, 050105 experimental psychology, Primary progressive aphasia, 03 medical and health sciences, Dementia aphasia, 0302 clinical medicine, Atrophy, Gyrus, Aphasia, Agrammatism, Internal medicine, medicine, 0501 psychology and cognitive sciences, Prospective cohort study, business.industry, 05 social sciences, respiratory system, medicine.disease, medicine.anatomical_structure, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: ObjectiveTo determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with GRN (progranulin) mutations and to study their neuroanatomic correlates.MethodsPatients with PPA carrying GRN mutations (PPA-GRN) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA.ResultsAmong the 235 patients with PPA, 45 (19%) carried GRN mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%).ConclusionsThis study shows that the most frequent PPA variant associated with GRN mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. GRN testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming GRN gene–specific therapies.
Published: 2021

21. Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications

Author: Fabienne Clot, Florence Pasquier, Didier Hannequin, Olivier Colliot, Armelle Rametti-Lacroux, Sophie Auriacombe, Raffaella Migliaccio, Ludmila Jornea, Marion Houot, Agnès Camuzat, Carole Azuar, Alexis Brice, Mathilde Sauvée, Philippe Martin-Hardy, Richard Levy, Philippe Couratier, Isabelle Le Ber, Jérémie Pariente, Claire Boutoleau-Bretonnière, Karim Dorgham, Dario Saracino, Bruno Dubois, Mira Didic, Daisy Rinaldi, Prev-Demals, David Wallon, Predict-PGRN study groups, Ftd-Als, Sylvie Forlani, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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], 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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), Université Lille 2 - Faculté de Médecine, CHU Limoges, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), CIC - Nantes, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), The research leading to these results received funding from the ’Investissements d’avenir’ ANR-11- INBS-0011. This work was partially funded by the Programme Hospitalier de Recherche Clinique (PHRC) Predict- PGRN (to ILB, promotion by Assistance Publique–Hôpitaux de Paris), the PHRC FTLD- exome (to ILB, promotion by Assistance Publique–Hôpitaux de Paris), by the ANR- PRTS PREV- DEMALS project (to ILB, grant number ANR-14- CE15-0016-07, promotion by Assistance Publique–Hôpitaux de Paris) and the Fondation Vaincre Alzheimer (to ILB, grant number FR-17035)., ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), 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'Immunologie et des Maladies Infectieuses (CIMI), Faculté de Médecine Henri Warembourg - Université de Lille, 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), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), Saracino, Dario, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease progression, Youden's J statistic, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Therapeutic trial, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, C9orf72, Internal medicine, Medicine, Biomarker (medicine), Surgery, Neurology (clinical), Amyotrophic lateral sclerosis, business, Trial registration, 030217 neurology & neurosurgery, 030304 developmental biology, Frontotemporal dementia
Abstract: ObjectiveNeurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.MethodsWe analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.ResultspNfL levels increased with age in controls, from ~5 to~18 pg/mL (pGRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.ConclusionsThis study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.Trial registration numbersNCT02590276 and NCT04014673.
Published: 2021

22. Clinical relevance of brain atrophy subtypes categorization in memory clinics

Author: Olivier Godefroy, François Tison, Yannick Béjot, Frédéric Blanc, David Wallon, Vincent Bouteloup, Clara Fischer, Marie-Odile Habert, Bruno Dubois, Mathilde Sauvée, Geneviève Chêne, Cédric Annweiler, Olivier Hanon, Vincent Planche, Carole Dufouil, J. Delrieu, Marie Chupin, Audrey Gabelle, Isabelle Jalenques, Pierre Krolak-Salmon, Matthieu Ceccaldi, Claire Paquet, Isabelle Bourdel-Marchasson, Florence Pasquier, Jean-François Mangin, Centre de résonance magnétique des systèmes biologiques (CRMSB), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
Subjects: Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], Ambulatory Care Facilities, Hippocampus, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Atrophy, Developmental Neuroscience, Alzheimer Disease, mental disorders, Humans, Medicine, Dementia, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Aged, Memory Disorders, Lewy body, business.industry, Health Policy, Brain, Cognition, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, Categorization, Cohort, Female, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract: Introduction The clinical relevance of brain atrophy subtypes categorization in non-demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. Methods A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. Results Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid-positive participants. Hippocampal-sparing and limbic-predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal-sparing and minimal/no atrophy groups. Discussion Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics.
Published: 2020

23. Current status and quantitative results of the AMYPAD prognostic and natural history study

Author: Juan Domingo Gispert, Pablo Martinez-Lage, Laure Saint-Aubert, Lisa Ford, Miia Kivipelto, José Luis Molinuevo, Florence Pasquier, Lyduine Collij, Philip Scheltens, Bruno Dubois, Marta Marquié, Katherine R. Gray, Julien Dumurgier, Rik Vandenberghe, Fiona Heeman, Craig W. Ritchie, Oriol Grau-Rivera, Peter Connelly, Frederik Barkhof, Michael Schöll, Giovanni B. Frisoni, Isadora Lopes Alves, Andrew W. Stephens, Bruno Vellas, Christopher Buckley, Pierre Payoux, Mercè Boada, Audrey Gabelle, Gemma Salvadó, Gill Farrar, Claire Boutoleau-Bretonnière, and Bernard Hanseeuw
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease progression, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Developmental Neuroscience, Neuroimaging, medicine, Neurology (clinical), Tracking (education), Geriatrics and Gerontology, business, Natural history study
Published: 2020

24. Pathways involved in the relationship between resilience and cognitive function: The Memento cohort

Author: Geneviève Chêne, Pierre Krolak Salmon, Claire Paquet, Audrey Gabelle, Florence Pasquier, Leslie Grasset, Frédéric Blanc, Cédric Annweiler, Olivier Hanon, Mathieu Ceccaldi, Carole Dufouil, Bruno Vellas, and Bruno Dubois
Subjects: Gerontology, medicine.medical_specialty, Epidemiology, Health Policy, Cognition, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, medicine, Neurology (clinical), Geriatrics and Gerontology, Resilience (network), Psychology
Published: 2020

25. Greater than the sum: Federated analyses in Alzheimer’s disease using the Human Brain Project Medical Informatics Platform (MIP)

Author: Florence Pasquier, Jean-François Démonet, Ferath Kherif, Thierry Phenix, Philippe Ryvlin, Alberto Redolfi, Jerome Chaptinel, Arseny A. Sokolov, and Melanie Leroy
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Developmental cognitive neuroscience, Disease, Human Brain Project, Health informatics, Clinical neurology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, medicine, Medical physics, Neurology (clinical), Geriatrics and Gerontology, business, Health policy
Published: 2020

26. The impact of culture on neuropsychological performance: A global social cognition study across 12 countries

Author: Anne Botzung, Sandra Baez, Ricardo F. Allegri, Begoña Indakoetxea, Catalina Trujillo, Lucia Crivelli, Fermin Moreno, Andrea Slachevsky, Sol Fittipaldi, Leonardo Cruz de Souza, Frédéric Blanc, François Quesque, Johan S. Grisales, Gada Musa, Alberto Benussi, Olga Iakovlena, Michael Hornberger, Maxime Bertoux, María Florencia Clarens, Antoine Coutrot, Antônio Lúcio Teixeira, Galina Prianishnikova, Junhua Liang, Thomas Duning, Ismael Calandri, David Huepe, Juan F. Cardona, Lina Zhao, Myriam Barandiaran, Luciana Cassimiro, Elena Lyashenko, Nahuel Magrath, Patricia Lillo, Paulo Caramelli, Thibaud Lebouvier, Anna Morozova, Nathalie Philippi, Carol Hudon, Florence Pasquier, Nadezda Veryugina, Adolfo M. García, Maura Cosseddu, Agustín Ibáñez, Fen Wang, Emma Flanagan, Hannah Mulet‐Perreault, Millena Vieira Brandão Moura, Carolina Delgado, Lucas Sedeño, Jennifer Kemp, Alejandra Neely-Prado, Sharon Cox, Mônica Sanches Yassuda, Andreas Johnen, and Barbara Borroni
Subjects: Epidemiology, Health Policy, media_common.quotation_subject, Neuropsychology, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Social cognition, Multiculturalism, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Psychology, media_common, Clinical psychology
Published: 2020

27. CSF biomarkers in neuropathological Alzheimer's disease

Author: Vincent Deramecourt, Thibaud Lebouvier, Claude Alain Maurage, Florence Pasquier, and Melanie Leroy
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Neuropathology, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Csf biomarkers, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2020

28. Overview of dominantly inherited AD and top‐line DIAN‐TU results of solanezumab and gantenerumab

Author: Didier Hannequin, Jared R. Brosch, B. Joy Snider, Anna Santacruz, Anne M. Fagan, Suman Jayadev, William S. Brooks, Colin L. Masters, Erik D. Roberson, Mario Masellis, Susan Mills, Christopher H. Dyck, Florence Pasquier, Paulo Fontoura, Bruno Dubois, Monika Baudler, Lawrence S. Honig, Doug R. Galasko, James J. Lah, Peter J. Snyder, David Wallon, Geoffrey A. Kerchner, Eric McDade, Guoqiao Wang, Andrew J. Aschenbrenner, Jason Hassenstab, Roy Yaari, Ghulam M. Surti, Raquel Sánchez-Valle, Jérémie Pariente, Stephen Salloway, Carlos Cruchaga, Randall J. Bateman, Ivonne Z. Jimenez-Velazquez, Robert A. Koeppe, John C. Morris, Serge Gauthier, Clifford R. Jack, Sarah B. Berman, Alison Goate, Catherine J. Mummery, Martin R. Farlow, Karen C. Holdridge, Rachelle S. Doody, Tammie L.S. Benzinger, Scott W. Andersen, Chengjie Xiong, Ging-Yuek Robin Hsiung, Roger Clarnette, Paul Delmar, Maïté Formaglio, Mark A. Mintun, Kelley Coalier, John R. Sims, Brian A. Gordon, and David B. Clifford
Subjects: Physics, Epidemiology, Health Policy, Geometry, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Solanezumab, Geriatrics and Gerontology, Line (text file), Gantenerumab, medicine.drug
Published: 2020

29. Association of Alzheimer's disease and amyotrophic lateral sclerosis: A series of cases and review of the literature

Author: Pierre Lozeron, Florence Pasquier, David Wallon, Vincent Deramecourt, Agathe Vrillon, Elodie Bouaziz Amar, and Claire Paquet
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Dermatology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Amyotrophic lateral sclerosis, business, Association (psychology)
Published: 2020

30. Alzheimer's disease phenotypes misdiagnosed with frontotemporal lobar degeneration: A retrospective neuropathologic study

Author: Claude Alain Maurage, Melanie Leroy, Florence Pasquier, Simon Lecerf, Vincent Deramecourt, Florence Lebert, and Thibaud Lebouvier
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Neuropathology, Frontotemporal lobar degeneration, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Clinical phenotype, business
Published: 2020

31. Dementia with Lewy bodies: Characteristics of the prodromal stage in a nationwide longitudinal cohort

Author: Anne Botzung, Izzie Jacques Namer, Carole Dufouil, Frédéric Blanc, Jean-François Dartigues, Catherine Martin-Hunyadi, Jean-François Mangin, Marie Chupin, Clara Fischer, Marie-Odile Habert, Paulo Loureiro de Sousa, Claire Paquet, Vincent Bouteloup, Mathieu Ceccaldi, Nathalie Philippi, Pierre Krolak Salmon, Florence Pasquier, Renaud David, David Wallon, Geneviève Chêne, Catherine Demuynck, Olivier Bousiges, Stéphane Kremer, Catherine Belin, Timothée Albasser, Olivier Moreaud, Mathilde Sauvée, Benjamin Cretin, and Audrey Gabelle
Subjects: medicine.medical_specialty, Epidemiology, Dementia with Lewy bodies, Behavioral neurology, business.industry, Health Policy, Prodromal Stage, Neuropsychiatry, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Longitudinal cohort, Psychiatry, business
Published: 2020

32. lncRNAs as a novel source of diagnostic applications for early Alzheimer’s disease and other dementia types

Author: Moira Marizzoni, Hüseyin Firat, Sabrina Danilin, Frédéric Blanc, Eloi Magnin, Jean-François Démonet, Hakan Gurvit, Bruno Dubois, Giovanni B. Frisoni, Eric Schordan, Florence Pasquier, Stéphanie Boutillier, François Sellal, Sami Ait Abbi Nazi, Jean Christophe Bier, Saliha Moussaoui, Audrey Gabelle, Catherine Mutter, Renaud David, and Adrian Ivanoiu
Subjects: Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Bioinformatics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2020

33. Solanezumab in‐depth outcomes

Author: Roger Clarnette, Ivonne Z. Jimenez-Velazquez, Ghulam M. Surti, Suman Jayadev, Anne M. Fagan, Clifford R. Jack, Peter J. Snyder, Christopher H. van Dyck, Erik D. Roberson, Guoqiao Wang, Mario Masellis, David B. Clifford, Chengjie Xiong, Randall J. Bateman, Jérémie Pariente, Tammie L.S. Benzinger, Ging-Yuek Robin Hsiung, Serge Gauthier, Rachelle S. Doody, Paul Delmar, Didier Hannequin, Doug R. Galasko, Sarah B. Berman, Florence Pasquier, Robert A. Koeppe, James J. Lah, Carlos Cruchaga, Paulo Fontoura, Alison Goate, Eric McDade, Raquel Sánchez-Valle, David Wallon, Dian‐Tu Study Team, Catherine J. Mummery, Colin L. Masters, Jared R. Brosch, Maïté Formaglio, B. Joy Snider, Susan Mills, Monika Baudler, Lawrence S. Honig, Bruno Dubois, John C. Morris, Kelley Coalier, Brian A. Gordon, Stephen Salloway, Andrew J. Aschenbrenner, Jason Hassenstab, Anna Santacruz, William S. Brooks, Geoffrey A. Kerchner, and Martin R. Farlow
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Solanezumab, Geriatrics and Gerontology, business, Gantenerumab, medicine.drug
Published: 2020

34. Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72 -associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Noémie Robil, Agnès Camuzat, Vincent Anquetil, Isabelle Le Ber, Ivan Moszer, Florence Pasquier, Philippe Couratier, Emmanuelle Becker, Ludmila Jornea, David Wallon, Olivier Colliot, Dario Saracino, Sylvie Forlani, Thomas Gareau, Daisy Rinaldi, Virgilio Kmetzsch, Pierre de la Grange, Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Service de Neurologie [CHU Limoges], CHU Limoges, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Rouen, Université de Lille, Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), GenoSplice [Paris], FRONTLAB: Fonctions et dysfonctions de systèmes frontaux [ICM Paris] (FRONTlab), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-14-CE15-0016,PREV-DEMALS,Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA)(2014), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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], 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), 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), École pratique des hautes études (EPHE), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FRONTlab - Systèmes frontaux : fonctions et dysfonctions (FRONTlab), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Kmetzsch, Virgilio, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, Appel à projets générique - Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA) - - PREV-DEMALS2014 - ANR-14-CE15-0016 - Appel à projets générique - VALID, Infrastructures - Institut français de bioinformatique - - IFB (ex Renabi-IFB)2011 - ANR-11-INBS-0013 - INBS - VALID, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), 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 de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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)-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), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Chromosome 9, Disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], C9orf72, Internal medicine, microRNA, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Mutation, business.industry, medicine.disease, [STAT.ML] Statistics [stat]/Machine Learning [stat.ML], Psychiatry and Mental health, Surgery, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: ObjectiveTo identify potential biomarkers of preclinical and clinical progression in chromosome 9 open reading frame 72 gene (C9orf72)-associated disease by assessing the expression levels of plasma microRNAs (miRNAs) in C9orf72 patients and presymptomatic carriers.MethodsThe PREV-DEMALS study is a prospective study including 22 C9orf72 patients, 45 presymptomatic C9orf72 mutation carriers and 43 controls. We assessed the expression levels of 2576 miRNAs, among which 589 were above noise level, in plasma samples of all participants using RNA sequencing. The expression levels of the differentially expressed miRNAs between patients, presymptomatic carriers and controls were further used to build logistic regression classifiers.ResultsFour miRNAs were differentially expressed between patients and controls: miR-34a-5p and miR-345-5p were overexpressed, while miR-200c-3p and miR-10a-3p were underexpressed in patients. MiR-34a-5p was also overexpressed in presymptomatic carriers compared with healthy controls, suggesting that miR-34a-5p expression is deregulated in cases with C9orf72 mutation. Moreover, miR-345-5p was also overexpressed in patients compared with presymptomatic carriers, which supports the correlation of miR-345-5p expression with the progression of C9orf72-associated disease. Together, miR-200c-3p and miR-10a-3p underexpression might be associated with full-blown disease. Four presymptomatic subjects in transitional/prodromal stage, close to the disease conversion, exhibited a stronger similarity with the expression levels of patients.ConclusionsWe identified a signature of four miRNAs differentially expressed in plasma between clinical conditions that have potential to represent progression biomarkers for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. This study suggests that dysregulation of miRNAs is dynamically altered throughout neurodegenerative diseases progression, and can be detectable even long before clinical onset.Trial registration numberNCT02590276.
Published: 2020

35. The Influence of Baseline Alzheimer's Disease Severity on Cognitive Decline and CSF Biomarkers in the NILVAD Trial

Author: Marcel G. M. Olde Rikkert, Michael Mullan, Ghania Ait-Ghezala, Daniel Paris, Laila Abdullah, Kaj Blennow, Florence Pasquier, Magda Tsolaki, Fiona Crawford, Suzanne Hendrix, Anders Wallin, Anne Börjesson-Hanson, Sean Kennelly, and Brian A. Lawlor
Subjects: 0301 basic medicine, medicine.medical_specialty, mild Alzheimer's disease, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Clinical Dementia Rating, Placebo, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, cerebrospinal fluid Aβ42/Aβ40 ratios, Internal medicine, mental disorders, medicine, Neurogranin, Cognitive decline, lcsh:Neurology. Diseases of the nervous system, Original Research, business.industry, Confounding, nilvadipine, exploratory analysis, cognitive decline, Nilvadipine, 3. Good health, Clinical trial, 030104 developmental biology, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Contains fulltext : 220566.pdf (Publisher’s version ) (Open Access) We examined the effects of a dihydropyridine calcium channel blocker nilvadipine with anti-inflammatory properties on cognition and cerebrospinal fluid (CSF) biomarkers by baseline Alzheimer's disease (AD) severity. Exploratory analyses were performed on the dataset (n = 497) of a phase III randomized placebo-controlled trial to examine the response to nilvadipine in AD subjects stratified by baseline AD severity into very mild (MMSE >/= 25), mild (MMSE 20-24) and moderate AD (MMSE < 20). The outcome measures included total and subscale scores of the Alzheimer's Disease Assessment Scale Cognitive 12 (ADAS-Cog 12), the Clinical Dementia Rating Scale sum of boxes (CDR-sb) and the AD composite score (ADCOMS). Cerebrospinal fluid biomarkers Abeta38, Abeta40, Abeta42, neurofilament light chain (NFL), neurogranin, YKL-40, total tau and P181 tau (ptau) were measured in a subset of samples (n = 55). Regression analyses were adjusted for confounders to specifically examine the influence of nilvadipine and baseline AD severity on cognitive outcomes over 78-weeks. Compared to their respective placebo-controls, nilvadipine-treated, very mild AD subjects showed less decline, whereas moderate AD subjects showed a greater cognitive decline on the ADAS-Cog 12 test and the ADCOMS. A lower decline was observed after nilvadipine treatment for a composite memory trait in very mild AD subjects and a composite language trait in mild AD subjects. Cerebrospinal fluid Abeta42/Abeta40 ratios were increased in mild AD and decreased in moderate AD patients treated with nilvadipine, compared to their respective controls. Among moderate AD subjects, levels of ptau, total tau, neurogranin and YKL-40 increased in subjects treated with nilvadipine compared to placebo. These studies suggest that baseline AD severity influenced the treatment outcome in the NILVAD trial and that future clinical trials of nilvadipine should be restricted to mild and very mild AD patients. Trial Registration: NCT02017340 Registered 20 December 2013, https://clinicaltrials.gov/ct2/show/NCT02017340 EUDRACT Reference Number 2012-002764-27 Registered 04 February 2013, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002764-27.
Published: 2020

36. Neurobiol Aging

Author: Pascaline Cassagnaud, David Wallon, Vincent Deramecourt, Florence Pasquier, Didier Hannequin, NeuroCEB Brain Bank, Thibaud Lebouvier, Sophie Auriacombe, Bruno Dubois, Mathieu Ceccaldi, Claude-Alain Maurage, Isabelle Le Ber, Marie Sarazin, Florence Lebert, Maxime Bertoux, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Aging, Pathology, medicine.medical_specialty, Amnesia, Autopsy, Disease, Neuropsychological Tests, SEPIA, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Memory, Predictive Value of Tests, medicine, Humans, Dementia, Cognitive decline, Pathological, Aged, Cued speech, Verbal Behavior, business.industry, General Neuroscience, Middle Aged, medicine.disease, 030104 developmental biology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Cues, Geriatrics and Gerontology, Verbal memory, medicine.symptom, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Amnesia is a key component of Alzheimer's disease (AD) and the most important feature of its clinical diagnosis but its specificity has recently been challenged. This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy. Patients' histological diagnoses were classified as pure AD, mixed AD, and non-AD pathologies. Data-driven automated classification procedures explored the correspondence between memory performance and pathological diagnoses. Classifications revealed 3 clusters of performance reflecting different levels of amnesia. Little correspondence between these clusters and the presence of AD pathology was retrieved. A third of patients with pure/mixed AD pathology were non-amnesic at presentation and ≈45% of patients without AD pathology were amnesic. Data-driven prediction of AD pathology based on memory also had a poor accuracy. Free and cued memory assessments are fair tools to diagnose an amnesic syndrome but lack accuracy to predict AD pathology.
Published: 2020

37. Antihypertensive agents in Alzheimer's disease: beyond vascular protection

Author: Patrick Duriez, Yaohua Chen, Régis Bordet, Florence Pasquier, and Thibaud Lebouvier
Subjects: medicine.medical_specialty, Disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Alzheimer Disease, Internal medicine, medicine, Secondary Prevention, Dementia, Humans, Pharmacology (medical), Cognitive decline, Stroke, Neprilysin, Antihypertensive Agents, Vascular disease, business.industry, General Neuroscience, medicine.disease, 030227 psychiatry, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Introduction: Midlife hypertension has been consistently linked with increased risk of cognitive decline and Alzheimer's disease (AD). Observational studies and randomized trials show that the use of antihypertensive therapy is associated with a lesser incidence or prevalence of cognitive impairment and dementia. However, whether antihypertensive agents specifically target the pathological process of AD remains elusive.Areas covered: This review of literature provides an update on the clinical and preclinical arguments supporting anti-AD properties of antihypertensive drugs. The authors focused on validated all classes of antihypertensive treatments such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers, diuretics, neprilysin inhibitors, and other agents. Three main mechanisms can be advocated: action on the concurrent vascular pathology, action on the vascular component of Alzheimer's pathophysiology, and action on nonvascular targets.Expert opinion: In 2019, while there is no doubt that hypertension should be treated in primary prevention of vascular disease and in secondary prevention of stroke and mixed dementia, the place of antihypertensive agents in the secondary prevention of 'pure' AD remains an outstanding question.
Published: 2019

38. [The French memory clinics network system]

Author: Chloé Rachez, Florence Pasquier, Maurice Hertzog, Anne Desprez, Philippe Bruniaux, and Catherine Adnet
Subjects: Mental Health Services, Medical education, Neurocognitive Disorders, Cognition, Disease, Integrated care, Neuropsychology and Physiological Psychology, Work (electrical), Software deployment, Multidisciplinary approach, Alzheimer Disease, Management system, Humans, Neurology (clinical), France, Geriatrics and Gerontology, Psychology, Neurocognitive, Biological Psychiatry, Aged
Abstract: In France, the management of patients with neurocognitive disorders is based on a network of memory clinics. The current operating mode is presented with projects aiming to its improvement, and potential evolution. Interviews were conducted at Memory resources and research centers (CMRR) as well as at the Regional health authorities (ARS) on organization, difficulties, innovation and projects for care management of patients suffering from Alzheimer's disease or related disorder. Twenty-seven semi-structured interviews were performed at the CMRR, and ten with the ARS. The collaboration with the medico-social and associative sectors was unequal. All CMRR were involved in clinical research. The links between ARS and CMRR were sometimes difficult with a lack of dialogue on the projects. However, many innovative plans have been led by the memory clinics and have sometimes been supported by the Health authorities: a therapeutic education program for patients with mild cognitive disorders, deployment of tele-medicine consultations to diagnose neurocognitive disorders in nursing home residents, setting of a network for management of behavioral disorders, creation of a mobile team specialized in clinical research, and creation of a multidisciplinary consultation following diagnosis to work on a personalized care plan. Experienced professionals mentioned a mature and efficient structure of the care management system thanks to the CMRRs' labeling and the different Alzheimer's national plans. However, this highly specialized system does not meet the demands of integrated care and should adapt to the increasing prevalence of patients. Therefore, structuration of primary care should be an emerging subject of reflection at national and international level.
Published: 2019

39. Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers

Author: Olivier Vercruysse, Claire Paquet, Audrey Gabelle, Xavier Delbeuck, Frederic Blanc, David Wallon, Julien Dumurgier, Eloi Magnin, Olivier Martinaud, Barbara Jung, Olivier Bousiges, Sylvain Lehmann, Constance Delaby, Muriel Quillard-Murain, Katell Peoc`h, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Didier Hannequin, Bernard Sablonniere, Luc Buee, Jacques Hugon, Susanna Schraen, Florence Pasquier, Stephanie Bombois, null for the e-PLM group, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Strasbourg (UNISTRA), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Université Paris Diderot - Paris 7 (UPD7), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], tau Proteins, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Diagnostic Errors, Phosphorylation, Vascular dementia, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Aged, Retrospective Studies, Hippocampal sclerosis, Amyloid beta-Peptides, business.industry, Brain, medicine.disease, Peptide Fragments, 3. Good health, Neurology, Mood disorders, Biomarker (medicine), Female, Neurology (clinical), Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies, Frontotemporal dementia
Abstract: Background: Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). Objective: The aim of this study was to test the hypothesis of misdiagnoses for these patients. Method: Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF Aβ1-42, T-tau and P-tau biomarkers and clinical follow-up, were included. Clinical and imaging data were reviewed by an independent board, from baseline (visit with clinical evaluation and CSF analysis) to the end of the follow-up, for a final diagnosis. Results: In the e-PLM cohort of 1098 AD patients with CSF analysis, 37 (3.3%) patients (20 with AD dementia core clinical criteria and 17 with AD-MCI core clinical criteria) had normal CSF biomarker profile and a clinical follow-up. All patients presented with episodic memory impairment and 27 (73%) had medial temporal lobe atrophy on MRI-scan. After a median follow-up of 36 months (range 7-74), the final diagnosis was AD MCI or dementia for 9 (24%) patients, and unlikely due to AD for 28 (76%) patients. A misdiagnosis was corrected in 18 (49%) patients (mood disorders, non-AD degenerative dementia, vascular cognitive impairment, alcohol cognitive disorders, temporal epilepsy and hippocampal sclerosis), and 10 (27%) patients had cognitive disorders of undetermined etiology. Conclusion: AD diagnosis (MCI or dementia) with normal CSF biomarkers is a rare condition. A clinical follow- up is particularly recommended to consider an alternative diagnosis.
Published: 2018

40. Update on tauopathies

Author: Thibaud Lebouvier, Luc Buée, and Florence Pasquier
Subjects: 0301 basic medicine, biology, business.industry, Tau protein, tau Proteins, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Text mining, Tauopathies, Neurology, mental disorders, biology.protein, Animals, Humans, Medicine, Dementia, Dementia diagnosis, Neurology (clinical), business, Pathological, Neuroscience, 030217 neurology & neurosurgery
Abstract: The purpose of this review is to provide an update on the role of tau beyond the stabilization of microtubules and on the clinical, pathological, diagnostic and therapeutic aspects of tauopathies.Beyond its function as a microtubule-associated tau protein, tau is also involved in gene regulation, signal transduction and metabolism. Experimental models allow for the development of new diagnostic and therapeutic tools. Tauopathies encompass different disorders that may manifest with various clinical syndromes. Differential diagnosis with other proteinopathies is still challenging. Cerebrospinal fluid biomarkers and radiotracers were extensively studied in the last year. Although diagnostic accuracy remains deceiving in non-Alzheimer's disease tauopathies, positron emission tomography tau tracers could be used to monitor disease progression.Despite the advent of novel therapeutic approaches and the increasing number of clinical trials in tauopathies, accurate clinical diagnosis is still an unmet need and better tau biomarkers are still desperately needed. Although primary taupathies are rare and heterogeneous disorders, their combined prevalence and the importance of tau disorder in Alzheimer's disease and secondary tauopathies makes research on tauopathy a priority - because it could benefit many patients.
Published: 2017

41. 18F-FDG PET hypometabolism patterns reflect clinical heterogeneity in sporadic forms of early-onset Alzheimer's disease

Author: Xavier Delbeuck, Renaud Lopes, Florence Pasquier, Franck Semah, Adeline Rollin Sillaire, Grégory Petyt, Aurélien Maureille, Matthieu Vanhoutte, Rachid Fahmi, Alice Jaillard, and Grégory Kuchcinski
Subjects: 0301 basic medicine, Aging, Paralimbic cortex, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Voxel, Clinical heterogeneity, medicine, Early-onset Alzheimer's disease, Prefrontal cortex, medicine.diagnostic_test, General Neuroscience, Neuropsychology, Cognition, Neuropsychological test, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Neurology (clinical), Geriatrics and Gerontology, Psychology, Neuroscience, computer, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Until now, hypometabolic patterns and their correlations with neuropsychological performance have not been assessed as a function of the various presentations of sporadic early-onset Alzheimer's disease (EOAD). Here, we processed and analyzed the patients' metabolic maps at the vertex and voxel levels by using a nonparametric, permutation method that also regressed out the effects of cortical thickness and gray matter volume, respectively. The hypometabolism patterns in several areas of the brain were significantly correlated with the clinical manifestations. These areas included the paralimbic regions for typical presentations of sporadic EOAD. For atypical presentations, the hypometabolic regions included Broca's and Wernicke's areas and the pulvinar in language forms, bilateral primary and higher processing visual regions (with right predominance) in visuospatial forms, and the bilateral prefrontal cortex in executive forms. Similar hypometabolism patterns were also observed in a correlation analysis of the 18F-FDG PET data versus domain-specific, neuropsychological test scores. These heterogeneities might reflect different underlying pathophysiological processes in particular clinical presentations of sporadic EOAD and should be taken into account in future longitudinal and therapeutic studies.
Published: 2017

42. Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates

Author: Didier Leys, Nicolas Durieux, Caroline Moreau, David Devos, Vincent Deramecourt, Jacques De Reuck, Régis Bordet, Claude-Alain Maurage, Florent Auger, Florence Pasquier, and Charlotte Cordonnier
Subjects: Male, Pathology, medicine.medical_specialty, Iron, Thalamus, Caudate nucleus, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, Amyotrophic lateral sclerosis, Aged, Cerebral Hemorrhage, Neuroradiology, Aged, 80 and over, medicine.diagnostic_test, business.industry, Amyotrophic Lateral Sclerosis, Brain, nutritional and metabolic diseases, Magnetic resonance imaging, General Medicine, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, Magnetic Resonance Imaging, nervous system diseases, Cerebrovascular Disorders, Subthalamic nucleus, Globus pallidus, Frontotemporal Dementia, Female, Neurology (clinical), Frontotemporal Lobar Degeneration, business, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.
Published: 2017

43. Cerebrovascular Lesions in Mixed Neurodegenerative Dementia: A Neuropathological and Magnetic Resonance Study

Author: Didier Leys, Claude-Alain Maurage, Vincent Deramecourt, Régis Bordet, Florent Auger, Florence Pasquier, Nicolas Durieux, Jacques De Reuck, and Charlotte Cordonnier
Subjects: Lewy Body Disease, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Mri studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Magnetic resonance study, Humans, Medicine, Aged, Cerebrovascular pathology, Aged, 80 and over, business.industry, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, nervous system diseases, Cerebrovascular Disorders, 030104 developmental biology, Neurology, Mixed dementia, Dementia, Female, Neurology (clinical), Lewy body pathology, Cerebral amyloid angiopathy, Neurodegenerative dementia, business, Lewy body disease, 030217 neurology & neurosurgery
Abstract: Background: In elderly brains of demented patients, Alzheimer and Lewy body pathology (LBP) are frequently associated. Cortical microinfarcts (CoMIs) are more observed in Lewy body disease, even in the absence of cerebral amyloid angiopathy (CAA). The present neuropathological and 7.0-tesla MRI studies investigate whether CoMIs are also more frequent in mixed neurodegenerative dementia syndromes. Summary: Both examinations revealed that CoMIs are increased to different degrees in mixed dementia syndromes according to the severity of the LBP. They were mainly associated with a trend of older age and arterial hypertension in the patients with the most severe LBP. Messages: The increased number of CoMIs in mixed dementia syndromes with LBP is mainly due to the associated cerebrovascular pathology, even in the absence of CAA.
Published: 2017

44. PARMAAJ : Parcours des patients présentant une maladie d’Alzheimer ou une maladie apparentée du sujet jeune

Author: Laetitia Breuilh, Catherine Adnet Bonte, Rollin-Sillaire Adeline, Florence Pasquier, Emilie Skrobala, and Brigitte Leprince
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction La Maladie d’Alzheimer et les Maladies Apparentees (MAMA) du sujet jeune ( Objectifs Les objectifs sont d’identifier les facteurs associes au delai diagnostique chez des patients jeunes ( Patients et methodes Des aidants de patients presentant une MAMA ( Resultats 162 patients ont ete inclus (CMRR : 111, âge de debut/diagnostic : 54,9/58,9 ans, MA : 82 %). Le delai diagnostique etait diminue quand la MA etait evoquee d’emblee (3 vs 4,5 ans), chez les patients a domicile (3,8 vs 6,2 ans) et chez ceux sans activite professionnelle aux premiers symptomes (3,5 vs 4,5 ans). Les patients hors CMRR desiraient moins participer a la recherche therapeutique (92 % vs 21,5 %). Les patients MA souhaitaient plus participer a la recherche clinique (80 % vs 40 %) et avaient plus de soutien (78,5 % vs 58,6 %). Discussion Le delai diagnostique de 4 ans semble peu modifie par « l’environnement » du malade (premiers medecins rencontres, niveau socioculturel, lieu de suivi, situations familiale/financiere/sociale, repercussion sur les proches) au moment des premiers symptomes et le type de maladie neurodegenerative qu’il presente. Les patients suivis au CMRR souhaitent davantage participer a la recherche notamment s’ils presentent une MA. Conclusion Evoquer un diagnostic de maladie neurodegenerative d’emblee chez les sujets jeunes permet de raccourcir le delai diagnostique. La formation des professionnels est donc le levier essentiel pour raccourcir ce delai.
Published: 2020

45. À fleur de peau

Author: Florence Pasquier, Claude-Alain Maurage, Adeline Rollin-Sillaire, Y. Chen, Aurore Braquet, and Thibaud Lebouvier
Subjects: 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2016

46. Diagnosis of severe cognitive disorder: the family history as a key issue

Author: Bertrand de Toffol, Celine Derollez, Stéphanie Bombois, Stéphane Haïk, and Florence Pasquier
Subjects: medicine.medical_specialty, Neurology, Bipolar Disorder, business.industry, Cognitive disorder, Dermatology, General Medicine, medicine.disease, Psychiatry and Mental health, Cognition, medicine, Key (cryptography), Humans, Family, Neurology (clinical), Neurosurgery, Family history, Psychiatry, business, Cognition Disorders, Neuroradiology
Published: 2019

47. O1‐06‐04: ASSOCIATION BETWEEN HYPERTENSION AND ALZHEIMER'S DISEASE AND RELATED CAUSES OF DEMENTIA: A PATHWAYS ANALYSIS IN THE MEMENTO COHORT

Author: Jérémie Lespinasse, Isabelle Rouch-Leroyer, Florence Pasquier, Olivier Moreaud, Audrey Gabelle, Jean-François Mangin, Athanasios Benetos, Pierre Vandel, Renaud David, Carole Dufouil, François Tison, Cédric Annweiler, Frédéric Blanc, Claire Paquet, Bruno Dubois, Cécile Proust-Lima, Olivier Hanon, Marie-Odile Habert, Geneviève Chêne, Pierre Jean Ousset, Marie Chupin, François Sellal, Olivier Godefroy, Isabelle Jalenques, Mathieu Ceccaldi, and Hugo Bertin
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cohort, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business, Association (psychology)
Published: 2019

48. Diagnostic positif et étiologique des démences frontotemporales

Author: Melanie Leroy, Florence Lebert, Florence Pasquier, Vincent Deramecourt, Maxime Bertoux, Thibaud Lebouvier, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, Neurology (clinical), 030217 neurology & neurosurgery, 3. Good health
Abstract: Resume Le diagnostic positif et etiologique de la variante comportementale des degenerescences lobaires frontotemporales (DLFT), egalement appele demence frontotemporale (DFTc), reste une gageure en 2019. Le diagnostic differentiel entre DFTc et troubles psychiatriques peut etre aide par l’utilisation stricte des criteres diagnostiques du DSM5 et quelques astuces semiologiques. Le diagnostic differentiel avec les presentations executives/comportementales de maladie d’Alzheimer (MA) est egalement difficile car les troubles de la memoire episodiques sont frequents dans la DFTc. En outre les biomarqueurs de MA du liquide cerebrospinal peuvent etre positifs en cas de co-pathologie ou faussement positifs dans certaines DFTc. Enfin le diagnostic etiologique des presentations cliniques de DFTc, qui peuvent correspondre a de multiples pathologies appartenant ou non au spectre des DLFT, est particulierement difficile. Du fait de leur frequence, la recherche de mutations GRN ou C9orf72 devrait etre proposee dans tous les cas de DFTc ; la recherche de mutations plus rares peut etre reservee aux cas precoces ou familiaux. Dans les cas sporadiques, certains phenotypes clinico-radiologiques associes aux DFTc doivent etre bien connus car predictifs de la pathologie sous-jacente, comme l’association a une pathologie motoneuronale dans les DFTc liees a une DLFT-TDP de type B. L’avenir verra le developpement de marqueurs cliniques, biologiques ou d’imagerie pour ameliorer les correlations clinicopathologiques et ouvrir la voie aux essais therapeutiques de traitements neuroprotecteurs.
Published: 2019

49. Neurite density is reduced in the presymptomatic phase of C9orf72 disease

Author: Anne Bertrand, Daisy Rinaldi, Olivier Colliot, Hui Zhang, Isabelle Le Ber, Alexandre Routier, Stanley Durrleman, Philippe Couratier, Florence Pasquier, Didier Hannequin, Daniel C. Alexander, Marion Houot, Jiaying Zhang, Junhao Wen, Sorbonne Université (SU), Centre for Medical Image Computing (CMIC), University College of London [London] (UCL), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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], 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), 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 Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pathology, medicine.medical_specialty, Neurite, business.industry, Frontotemporal lobar degeneration, Grey matter, medicine.disease, White matter, [STAT]Statistics [stat], 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Atrophy, medicine.anatomical_structure, C9orf72, Medicine, Surgery, [INFO]Computer Science [cs], Neurology (clinical), Amyotrophic lateral sclerosis, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: ObjectiveTo assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation.MethodsThe PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis) study is a prospective, multicentre, observational study of first-degree relatives of individuals carrying the C9orf72 mutation. Sixty-seven participants (38 presymptomatic C9orf72 mutation carriers (C9+) and 29 non-carriers (C9−)) were included in the present cross-sectional study. Each participant underwent one single-shell, multishell diffusion MRI and three-dimensional T1-weighted MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, grey matter volume and free water fraction between C9+ and C9− individuals were assessed using linear mixed-effects models.ResultsCompared with C9−, C9+ demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. Effect size was significantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a significantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy.ConclusionsNODDI provides higher sensitivity and greater tissue specificity compared with conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase.Trial registration numberNCT02590276.
Published: 2019

50. Aging and cerebrovascular lesions in pure and in mixed neurodegenerative and vascular dementia brains: a neuropathological study

Author: Florence Pasquier, Régis Bordet, Didier Leys, Claude-Alain Maurage, Vincent Deramecourt, Jacques De Reuck, and Charlotte Cordonnier
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Aging, Neuropathology, Disease, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Medicine, Dementia, Humans, cardiovascular diseases, Vascular dementia, Pathological, Aged, Aged, 80 and over, business.industry, Brain, Neurodegenerative Diseases, Frontotemporal lobar degeneration, medicine.disease, Cerebrovascular Disorders, 030104 developmental biology, Cerebral hemisphere, Female, Neurology (clinical), Cerebral amyloid angiopathy, business, 030217 neurology & neurosurgery
Abstract: Introduction The prevalence of dementia is increasing in our aging population. Because of the complexity of disease pathology, dementia classifications remain controversial. The present post-mortem study investigates whether there are age differences between dementia brains with a single pure neurodegenerative or cerebrovascular disease and those with mixed pathological features. Also, the impact of these vascular lesions is compared. Material and methods A total of 132 dementia brains with a pure neurodegenerative or cerebrovascular disease and 84 with mixed features were examined. Main age and gender distribution were compared between the overall group of pure and of mixed dementia. Also, the most common subgroups were compared separately. In addition to the detection of macroscopic visible lesions, a whole coronal section of a cerebral hemisphere, at the level of the mamillary body, was taken for semi-quantitative microscopic evaluation of white matter changes (WMCs), cortical micro-bleeds (CoMBs), and cortical micro-infarcts (CoMIs). Results Overall, patients with mixed dementia were at death significantly older than those with pure dementia. According to the main diagnosis, the pure forms of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) were more common in the younger age groups while in the older ones the mixed form of Lewy body disease (LBD) predominated. Neuropathological examination revealed an increased severity of cerebral amyloid angiopathy (CAA), territorial infarcts, lobar haematomas, and CoMIs in the mixed AD group. In FTLD only CoMIs were increased in the mixed group, while in LBD no differences in severity of all cerebrovascular lesions were observed. Lacunar infarcts were more frequent in pure vascular dementia, while CAA predominated in the mixed one. Conclusions Mixed dementia during the aging process is mainly due to the severity of AD and LBD pathologies combined with CAA-related cerebrovascular lesions.
Published: 2018

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