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132 results on '"Mira Didic"'

1. Primary progressive aphasias associated with C9orf72 expansions: Another side of the story

Author: idier Hannequin, Eino Solje, Sabrina Sayah, Emmanuel Gerardin, Marie Sarazin, Florence Pasquier, Marion Houot, Assi-Hervé Oya, Martine Vercelletto, Julien Lagarde, Marie Noguès-Lassiaille, Marie Chupin, Vincent Deramecourt, Sophie Auriacombe, Agnès Camuzat, Marc Teichmann, Jérémie Pariente, Sophie Ferrieux, Lucette Lacomblez, Mathieu Chastan, Jacques Monteil, Yaohua Chen, Marie-Paule Boncoeur, Lorenzo Cipriano, Anne Bissery, Simona Bottani, David Wallon, Christine Delmaire, Carole Roué-Jagot, Benjamin Le Toullec, Bernard-François Michel, Grégory Petyt, Olivier Martinaud, Philippe Couratier, Dario Saracino, Adeline Rollin-Sillaire, Daisy Rinaldi, Mira Didic, Serge Belliard, Amandine Géraudie, Géraldine Lautrette, Frédérique Etcharry-Bouyx, Xavier Delbeuck, Richard Levy, Frédéric Blanc, Mathieu Ceccaldi, Christel Thauvin-Robinet, Marie-Odile Habert, Eve Benchetrit, Maïté Formaglio, Alexis Brice, Isabelle Le Ber, Charles Duyckaerts, Véronique Golfier, Raffaella Migliaccio, Marie-Anne Mackowiak, Catherine Thomas-Antérion, Anne Bertrand, Olivier Colliot, François Sellal, Claire Boutoleau-Bretonnière, Anne M. Remes, Hugo Bertin, Aurélie Funkiewiez, and Stéphanie Bombois
Subjects: medicine.medical_specialty, C9orf72 Protein, Apraxias, Cognitive Neuroscience, Inferior frontal gyrus, Experimental and Cognitive Psychology, Frontotemporal lobar degeneration, respiratory system, Audiology, medicine.disease, Magnetic Resonance Imaging, Apraxia, Primary progressive aphasia, Aphasia, Primary Progressive, Neuropsychology and Physiological Psychology, Atrophy, C9orf72, medicine, Humans, Speech, Orbitofrontal cortex, Psychology, Language, Frontotemporal dementia
Abstract: C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them. This study depicts the spectrum of C9orf72–related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant. Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.
Published: 2021

2. Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression

Author: Walid Khrouf, Dario Saracino, Benoit Rucheton, Marion Houot, Fabienne Clot, Daisy Rinaldi, Joana Vitor, Marie Huynh, Evelyne Heng, Dimitri Schlemmer, Florence Pasquier, Vincent Deramecourt, Sophie Auriacombe, Carole Azuar, Richard Levy, Stéphanie Bombois, Claire Boutoleau-Brétonnière, Jérémie Pariente, Mira Didic, David Wallon, Frédérique Fluchère, Stéphane Auvin, Imen Ben Younes, Yann Nadjar, Alexis Brice, Bruno Dubois, Dominique Bonnefont-Rousselot, Isabelle Le Ber, and Foudil Lamari
Subjects: Neurology
Published: 2023

3. Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic

Author: Laure Delaval, Karine Nguyen, J. Cogez, Romain Schneckenburger, Eric Jouvent, Valérie Lauer, Fatoumata Ba, Matthias Lamy, Cédric Urbanczyk, Igor Raynouard, Françoise Bergametti, Jérémie Dassa, Livia Lanotte, Valérie Layet, Elisabeth Tournier-Lasserve, Jean Philippe Neau, Mira Didic, Alexandru Florea, Cédric Gollion, Carmen Badiu, Thibault Coste, Dominique Hervé, Nathalie Derache, and Maude Grelet
Subjects: Male, Proband, Genetics, Heterozygote, Mutation, Brain, High-Temperature Requirement A Serine Peptidase 1, Middle Aged, Biology, medicine.disease_cause, Penetrance, eye diseases, Stop codon, Pedigree, Frameshift mutation, Codon, Nonsense, medicine, Humans, Missense mutation, Female, Neurology (clinical), Allele, Frameshift Mutation, Haploinsufficiency, Aged
Abstract: Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease (CSVD) whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known CSVD genes, including HTRA1, in 3853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 mRNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases: gnomAD v3.1.1 [P = 3.12 × 10−17, odds ratio (OR) = 21.9], TOPMed freeze 5 (P = 7.6 × 10−18, OR = 27.1) and 1000 Genomes (P = 1.5 × 10−5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counselling.
Published: 2021

4. Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

Author: Schramm, Catherine, Charbonnier, Camille, Zaréa, Aline, Lacour, Morgane, Wallon, David, Boland, Anne, Deleuze, Jean-François, Olaso, Robert, Alarcon, Flora, Campion, Dominique, Nuel, Grégory, Nicolas, Gaël, Collaborators Daniela Andriuta, Pierre, Anthony, Sophie, Auriacombe, Anna-Chloé, Balageas, Guillaume, Ballan, Mélanie, Barbay, Emilie, Beaufils, Yannick, Béjot, Serge, Belliard, Marie, Benaiteau, Karim, Bennys, Frédéric, Blanc, Stéphanie, Bombois, Claire Boutoleau Bretonnière, Pierre, Branger, Jasmine, Carlier, Leslie, Cartz-Piver, Pascaline, Cassagnaud, Giovanni, Castelnovo, Christine, Champion, Annabelle, Chaussenot, Mathieu, Ceccaldi, Valérie, Chauviré, Yaohua, Chen, Julien, Cogez, Emmanuel, Cognat, Fabienne, Contegal-Callier, Lea, Corneille, Philippe, Couratier, Hélène, Courtemanche, Benjamin, Cretin, Charlotte, Crinquette, Bernard, Croisille, Benjamin, Dauriat, Sophie, Dautricourt, Vincent de la Sayette, Astrid De Liège, Marie De Verdal, Didier, Deffond, Benoit, Delpont, Florence, Demurger, Vincent, Deramecourt, Céline, Derollez, Mira, Didic, Giulia, Diemert, Elsa, Dionet, Philippe, Diraison, Aude, Doan, Martine Doco Fenzy, Boris, Dufournet, Julien, Dumurgier, Hélène, Durand, Anas, Dutray, Frédérique, Etcharry-Bouyx, Maté, Formaglio, Audrey, Gabelle, Anne, Gainche-Salmon, Jean-Claude, Getenet, Emmanuelle, Ginglinger, Olivier, Godefroy, Mathilde, Graber, Chloé, Gregoire, Stephan, Grimaldi, Julien, Gueniat, Claude, Gueriot, Sophie, Haffen, Lorraine, Hamelin, Didier, Hannequin, Cezara, Hanta, Clémence, Hardy, Geoffroy, Hautecloque, Camille, Heitz, Claire, Hourregue, Thérèse, Jonveaux, Snejana, Jurici, Catia, Khoumri, Lejla, Koric, Pierre, Krolak-Salmon, Pierre, Labauge, Morgane, Lacour, Julien, Lagarde, Hélène-Marie, Lanoiselée, Brice, Laurens, Isabelle Le Ber, Gwenaël Le Guyader, Amélie, Leblanc, Thibaud, Lebouvier, Anas, Lippi, Marie-Anne, Mackowiak, Eloi, Magnin, Cecilia, Marelli, Olivier, Martinaud, Aurélien, Maureille, Emilie, Milongo-Rigal, Sophie, Mohr, Hélène, Mollion, Olivier, Moreaud, Alexandre, Morin, Gaël, Nicolas, Julia, Nivelle, Camille, Noiray, Elisabeth, Ollagnon-Roman, Claire, Paquet, Jérémie, Pariente, Florence, Pasquier, Alexandre, Perron, Nathalie, Philippi, Virginie, Pichon, Vincent, Planche, Céline, Poirsier, Marie, Rafiq, Pauline, Rod-Olivieri, Adeline, Rollin-Sillaire, Carole, Roué-Jagot, Dario, Saracino, Marie, Sarazin, Mathilde, Sauvée, François, Sellal, Lila Sirven Villaros, Christel, Thauvin, Camille, Tisserand, Christophe, Tomasino, Cédric, Turpinat, Laurène Van Damme, Olivier, Vercruysse, Alice, Voilly, Nathalie, Wagemann, David, Wallon, Aline, Zarea, Shahzad, Ahmad, Philippe, Amouyel, Claudine, Berr, Anne, Boland, Paola, Bossu, Femke, Bouwman, Jose, Bras, Dominique, Campion, Camille, Charbonnier, Jordi, Clarimon, Antonio, Daniele, Jean-François, Dartigues, Stéphanie, Debette, Jean-François, Deleuze, Nicola, Denning, Oriol, Dols-Icardo, Nick, C Fox, Daniela, Galimberti, Emmanuelle, Génin, Hans, Gille, Benjamin, Grenier-Boley, Detelina, Grozeva, Rita, Guerreiro, John, J Hardy, Clive, Holmes, Henne, Holstege, Marc, Hulsman, Holger, Hummerich, M Arfan Ikram, M Kamran Ikram, Iris, Jansen, Amit, Kawalia, Robert, Kraaij, Jean-Charles, Lambert, Marc, Lathrop, Afina, W Lemstra, Alberto, Lleo, Lauren, Luckcuck, Marcel M A, M Mannens, Rachel, Marshall, Carlo, Masullo, Simon, Mead, Mecocci, Patrizia, Alun, Meggy, Merel, O Mol, Kevin, Morgan, Benedetta, Nacmias, Penny, J Norsworthy, Pau, Pastor, Olivier, Quenez, Alfredo, Ramirez, Rachel, Raybould, Richard, Redon, Marcel J, T Reinders, Anne-Claire, Richard, Steffi, G Riedel-Heller, Fernando, Rivadeneira, Stéphane, Rousseau, Natalie, S Ryan, Salha, Saad, Pascual, Sanchez-Juan, Philip, Scheltens, Jonathan, M Schott, Davide, Seripa, Daoud, Sie, Rebecca, Sims, Erik, Sistermans, Sandro, Sorbi, Resie van Spaendonk, Gianfranco, Spalleta, Nicćolo, Tesi, Betty, Tijms, André, G Uitterlinden, Wiesje, M van der Flier, Sven, J van der Lee, Cornelia, M van Duijn, Jeroen G, J van Rooij, John, C van Swieten, Pieter, J de Visser, Michael, Wagner, and Julie, Williams
Subjects: Genotype, Membrane Transport Proteins, Penetrance, Lifetime risk, Pedigree, Expectation-maximization algorithm, Settore MED/26 - NEUROLOGIA, Apolipoproteins E, Missing genotypes, Alzheimer Disease, Case-Control Studies, SORL1, Alzheimer, Genetics, Humans, Molecular Medicine, Molecular Biology, LDL-Receptor Related Proteins, APOE, Genetics (clinical)
Abstract: Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data. Conclusions We conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications.
Published: 2022

5. 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

6. A comparison of two statistical mapping tools for automated brain fdg-pet analysis in predicting conversion to alzheimer’s disease in subjects with mild cognitive impairment

Author: Paolo Bosco, Osman Ratib, Robert Perneczky, Giovanni B. Frisoni, Mira Didic, Gabriel Gold, Alexander Drzezga, Sara Trombella, Alberto Redolfi, Panteleimon Giannakopoulos, Valentina Garibotto, Silvia Morbelli, Flavio Nobili, Olivier Rager, Luigi Antelmi, Rik Ossenkoppele, Bart N.M. van Berckel, Claire Tabouret-Viaud, Eric Guedj, Université de Genève = University of Geneva (UNIGE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRCCS Fondazione Stella Maris [Pisa], IRCCS Fatebenefratelli - Brescia, IRCCS Istituto Giannina Gaslini [Genoa, Italy], Technische Universität München = Technical University of Munich (TUM), Imperial College London, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), University of Cologne, VU University Medical Center [Amsterdam], Otten, Lisa, Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Neurology, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, 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: Male, hypometabolic pattern, Concordance, [SDV]Life Sciences [q-bio], Disease, computer.software_genre, 030218 nuclear medicine & medical imaging, Correlation, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Alzheimer Disease, Fluorodeoxyglucose F18, Voxel, medicine, Humans, Dementia, Cognitive Dysfunction, Alzheimer’s disease, Automated analysis, FDG-PET, Hypometabolic pattern, MCI, Tatistical parametric mapping, Aged, Sweden, Brain Mapping, Models, Statistical, tatistical parametric mapping, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Statistical mapping, Brain, Gold standard (test), Alzheimer's disease, medicine.disease, Neurology, Positron-Emission Tomography, Disease Progression, Female, Neurology (clinical), Radiopharmaceuticals, business, Nuclear medicine, computer, 030217 neurology & neurosurgery
Abstract: Objective: Automated voxel-based analysis methods are used to detect cortical hypometabolism typical of Alzheimer’s Disease (AD) on FDG-PET brain scans. We compared the accuracy of two clinically validated tools for their ability to identify those MCI subjects progressing to AD at followup, to evaluate the impact of the analysis method on FDG-PET diagnostic performance. Methods: SPMGrid and BRASS (Hermes Medical Solutions, Stockholm, Sweden) were tested on 131 MCI and elderly healthy controls from the EADC PET dataset. The concordance between the tools was tested by correlating the quantitative parameters (z- and t-values), calculated by the two software tools, and by measuring the topographical overlap of the abnormal regions (Dice score). Three independent expert readers blindly assigned a diagnosis based on the two map sets. We used conversion to AD dementia as the gold standard. Results: The t-map and z-map calculated with SPMGrid and BRASS, respectively, showed a good correlation (R > .50) for the majority of individual cases (128/131) and for the majority of selected regions of interest (ROIs) (98/116). The overlap of the hypometabolic patterns from the two tools was, however, poor (Dice score .36). The diagnostic performance was comparable, with BRASS showing significantly higher sensitivity (.82 versus .59) and SPMGrid showing higher specificity (.87 versus .52). Conclusion: Despite similar diagnostic performance in predicting conversion to AD in MCI subjects, the two tools showed significant differences, and the maps provided by the tools showed limited overlap. These results underline the urgency for standardization across FDG-PET analysis methods for their use in clinical practice.
Published: 2020

7. Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe

Author: Chiara Cerami, Perminder S. Sachdev, Katrin Seeher, Nicole Kustyniuk, Paul K. Crane, Sandra Weintraub, Manfred Berres, Giovanni B. Frisoni, Ingo Kilimann, Alessandra Dodich, Clarissa Ferrari, Walter A. Kukull, Martina Pigliautile, Bruno Dubois, Mira Didic, David P. Salmon, Leonardo Sacco, Cristina Festari, Liesbeth Aerts, Stefan Klöppel, Emiliano Albanese, Nicola Girtler, Nicola Ballhausen, Andreas U. Monsch, Patrizia Mecocci, Alessio Toraldo, Fabricio Ferreira de Oliveira, Alice Grazia, Inez H.G.B. Ramakers, Jean-Marie Annoni, Flavio Nobili, EwXjLab caQTbQe, Kwun Chuen Gary Chan, Valentina Nicolosi, Bengt Winblad, Christian Chicherio, Michael Wagner, Suzie Diener, Jean Georges, Nicole A. Kochan, Stefano F. Cappa, Henry Brodaty, Daniel Ferreira, Eric Westman, Matthias Kliegel, Stefan J. Teipel, Daniele Altomare, Steven D. Shirk, Nathalie Mella, Andrea Brioschi-Guevara, Jean-François Démonet, Marina Boccardi, Isabelle Bos, Oliver Peters, Pieter Jelle Visser, Anton F. Gietl, Andreas Buchmann, Virginie Descloux, Lutz Froelich, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developmental Psychology, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: 050103 clinical psychology, Epidemiology, diagnosis, Consensus Development Conferences as Topic, standard neuropsychological assessment, Datasets as Topic, Disease, Neuropsychological Tests, Alzheimer&apos, cognitive assessment, 0302 clinical medicine, Cognition, MONTE-CARLO, BEHAVIORAL VARIANT, Neuropsychological assessment, SELECTIVE REMINDING TEST, Cognitive impairment, 610 Medicine & health, ComputingMilieux_MISCELLANEOUS, Language, medicine.diagnostic_test, Health Policy, 05 social sciences, Age Factors, standards [Neuropsychological Tests], Alzheimer's disease, Europe, ALZHEIMERS-DISEASE, Psychiatry and Mental health, classification [Cognitive Dysfunction], Educational Status, DIFFERENTIAL-DIAGNOSIS, Psychology, Alzheimer’s disease, Frontotemporal dementia, Clinical psychology, standards [Datasets as Topic], CONSENSUS STATEMENT, Harmonization, Article, s disease, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sex Factors, mild cognitive impairment, Developmental Neuroscience, AMNESTIC SYNDROME, medicine, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, ddc:610, mild neurocognitive disorders, DATA SET UDS, Expert Testimony, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, COGNITIVE IMPAIRMENT, diagnosis [Cognitive Dysfunction], Sample size determination, SAMPLE-SIZE, Normative, Neurology (clinical), Geriatrics and Gerontology, Neurocognitive, 030217 neurology & neurosurgery
Abstract: Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.
Published: 2022

8. 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

9. Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients

Author: Marco Salvatore, Marco Aiello, Diego Albani, Ilaria Boscolo Galazzo, Olivier Blin, Pradeep J. Nathan, Francesca B. Pizzini, Melissa Romano, Andrea Soricelli, Mira Didic, Gianluigi Forloni, Jill C. Richardson, Michela Pievani, Giovanni B. Frisoni, Jorge Jovicich, Giulia Quattrini, Moira Marizzoni, Xavier Golay, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), University of Brescia, Università degli studi di Verona = University of Verona (UNIVR), IRCCS SDN Napoli, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Università degli Studi di Napoli 'Parthenope' = University of Naples (PARTHENOPE), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Assistance Publique - Hôpitaux de Marseille (APHM), UCL Institute of Neurology, Queen Square [London], University of Trento [Trento], University of Cambridge [UK] (CAM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), and Université de Genève = University of Geneva (UNIGE)
Subjects: 0301 basic medicine, Apolipoprotein E, Male, medicine.medical_specialty, Perfusion scanning, Hippocampus, Alzheimer’s disease, arterial spin labeling, brain perfusion, default mode network, limbic network, mild cognitive impairment, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Limbic System, Memory impairment, Humans, Cognitive Dysfunction, Default mode network, Alzheimer's disease, Aged, Amnesia, Biomarkers, Cerebrovascular Circulation, Female, Magnetic Resonance Imaging, Default Mode Network, Perfusion, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, Discriminant validity, General Medicine, Hyperintensity, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Convergent validity, Cerebral blood flow, Cardiology, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer’s disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). Objective: To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. Methods: We collected core AD markers (amyloid-β 42 [Aβ42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks’ perfusion, cerebellar volume, and processing speed. Results: Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aβ42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = –0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. Conclusion: Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.
Published: 2021

10. A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment

Author: Ludovic Gardy, Emmanuel J. Barbeau, Mira Didic, Sven Joubert, Isabelle Rouleau, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-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), Service de neurochirurgie [CHU Marseille], Université de la Méditerranée - Aix-Marseille 2-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), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Neurology, Cognitive Neuroscience, naming, [SHS.PSY]Humanities and Social Sciences/Psychology, Experimental and Cognitive Psychology, Audiology, behavioral disciplines and activities, 050105 experimental psychology, Mini Mental Status Examination, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), mental disorders, medicine, Developmental and Educational Psychology, Semantic memory, 0501 psychology and cognitive sciences, 10. No inequality, Cognitive impairment, semantic memory, 05 social sciences, Neuropsychology, Alzheimer's disease, Random effects model, MCI, Feature (linguistics), meta-analysis, Neuropsychology and Physiological Psychology, Meta-analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; Introduction: Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Methods: Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. Results: 22 studies (476 healthy participants, 476 MCI patients, mean MMSE of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Discussion: Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.
Published: 2021

11. Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer’s Disease1

Author: Gianmario Sambuceti, Cathrine Jonsson, Patrizia Mecocci, Mira Didic, Robert Perneczky, Matteo Pardini, Bart N.M. van Berckel, Dario Arnaldi, Federico Massa, Giovanni B. Frisoni, Matteo Grazzini, Marco Pagani, Rik Ossenkoppele, Matteo Bauckneht, Alexander Drzezga, Eric Guedj, Fabrizio De Carli, Andrea Brugnolo, Samantha Galluzzi, Massimo E. Dottorini, S. Morbelli, Flavio Nobili, and Andrea Chincarini
Subjects: 0301 basic medicine, Receiver operating characteristic, business.industry, General Neuroscience, Youden's J statistic, General Medicine, Statistical parametric mapping, computer.software_genre, Support vector machine, 03 medical and health sciences, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, 0302 clinical medicine, Neuroimaging, Region of interest, Voxel, Medicine, Geriatrics and Gerontology, Verbal memory, business, Nuclear medicine, computer, 030217 neurology & neurosurgery
Abstract: Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [ 18 ]F-FDG-PET. Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. Methods: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [ 18 ]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). Results: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. Conclusion: The study confirms the good accuracy of [ 18 ]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.
Published: 2019

12. Plasma NfL levels and longitudinal change rates in

Author: Dario, Saracino, Karim, Dorgham, Agnès, Camuzat, Daisy, Rinaldi, Armelle, Rametti-Lacroux, Marion, Houot, Fabienne, Clot, Philippe, Martin-Hardy, Ludmila, Jornea, Carole, Azuar, Raffaella, Migliaccio, Florence, Pasquier, Philippe, Couratier, Sophie, Auriacombe, Mathilde, Sauvée, Claire, Boutoleau-Bretonnière, Jérémie, Pariente, Mira, Didic, Didier, Hannequin, David, Wallon, Olivier, Colliot, Bruno, Dubois, Alexis, Brice, Richard, Levy, and Sylvie, Forlani
Subjects: Adult, Aged, 80 and over, Male, C9orf72 Protein, Amyotrophic Lateral Sclerosis, Middle Aged, Progranulins, Neurofilament Proteins, Frontotemporal Dementia, Disease Progression, Humans, Female, Neurogenetics, Aged
Abstract: Objective Neurofilament 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. Methods We 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. Results pNfL levels increased with age in controls, from ~5 to~18 pg/mL (p
Published: 2021

13. 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

14. 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

15. Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study

Author: Bernhard W. Müller, Daniele Altomare, Marco Salvatore, Renaud Lopes, Paolo Maria Rossini, Jens Wiltfang, Moira Marizzoni, Martina Montalti, Stéphanie Bombois, Giovanni B. Frisoni, Clarissa Ferrari, Karl Titus Hoffmann, Camillo Marra, Massimo Caulo, Francesca B. Pizzini, David Bartrés-Faz, Ute Fiedler, Antonio Ferretti, Mira Didic, Manos Constantinidis, Andrea Soricelli, Federica Ribaldi, Joost P.A. Kuijer, Carlo Cavaliere, Antonios Drevelegas, Flavio Nobili, Piero Floridi, Luca Roccatagliata, Julien Sein, Régis Bordet, Franco Alessandrini, Pierre Payoux, Roberto Tarducci, Jorge Jovicich, Olivier Blin, Agnese Picco, Jean-Philippe Ranjeva, Frederik Barkhof, Beatriz Bosch, Magda Tsolaki, Pieter Jelle Visser, Lucilla Parnetti, Tilman Hensch, Jill C. Richardson, Núria Bargalló, Anna Mega, Helene Gros-Dagnac, Marco Aiello, Peter Schönknecht, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Center for Mind/Brain Sciences (CIMEC), University of Trento [Trento], Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), University of Verona (UNIVR), IRCCS SDN Napoli, Department of Clinic Sciences and Bioimaging, University G. d'Annunzio Chieti-Pescara, Interbalkan Medical Center of Thessaloniki, Dept. of Child and Adolescent Psychiatry and Psychology, Institut Clinic of Neurosciences IDIBAPS (Institut d'Investigacions Biomèdiques August Pi Sunyer), Hospital Clínic Universitari of Barcelona, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Department of Neuroscience, Catholic University, Roma, Centre for Medical Image Computing (CMIC), University College of London [London] (UCL), Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], 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], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), University Medical Center Göttingen (UMG), Department of Neuroradiology, University Hospital Leipzig, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Neurology Department, Hospital Clinic, IDIBAPS, Facultad de Medicina, Barcelona, Dept. Neuroscience & Neurorehabilitation, IRCCS-San Raffaele-Pisana, Rome, University of Leipzig Medical Center, Neuroradiology Unit, Perugia General Hospital, Perugia, Alzheimer Center Amsterdam, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Medical Physics Unit, Perugia General Hospital, Perugia, Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli studi di Genova = University of Genoa (UniGe), Università degli studi di Verona = University of Verona (UNIVR), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], 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)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Leipzig University, Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Adult, Male, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Image Processing, Medizin, Biomedical Engineering, Biophysics, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Automation, 0302 clinical medicine, Computer-Assisted, Sørensen–Dice coefficient, Image Processing, Computer-Assisted, White matter hyperintensities, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Lesion segmentation toolbox, ComputingMilieux_MISCELLANEOUS, Accuracy, Reproducibility, Lesion segmentation, business.industry, Lesion growth, Automated segmentation algorithms, Multi site, Reproducibility of Results, Gold standard (test), White Matter, Magnetic Resonance Imaging, Hyperintensity, Settore MED/26 - NEUROLOGIA, Cross-Sectional Studies, Algorithms, Female, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract: Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was −0.22[IQR = 0.50] for LGA-SPM8, −0.12[0.57] for LGA-SPM12, −0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.
Published: 2021

16. Amygdalar nuclei and hippocampal subfields on MRI: Test‐retest reliability of automated segmentation in old and young healthy volunteers

Author: Agnese Picco, Núria Bargalló, Antonios Drevelegas, Mira Didic, Régis Bordet, Moira Marizzoni, Bernhard W. Müller, Piero Floridi, Björn H. Schott, Michela Pievani, Giovanni B. Frisoni, Jill C. Richardson, Alberto Beltramello, Tilman Hensch, Marco Salvatore, Flavio Nobili, Pierre Payoux, Roberto Tarducci, Jorge Jovicich, Magda Tsolaki, Karl-Titus Hoffmann, Jens Wiltfang, Camillo Marra, Renaud Lopes, Jean-Philippe Ranjeva, Pieter Jelle Visser, Giulia Quattrini, Lucilla Parnetti, Manos Constantinides, Frederik Barkhof, David Bartrés-Faz, Francesca B. Pizzini, Julien Sein, Antonio Ferretti, Olivier Blin, Ute Fiedler, Luca Roccatagliata, Massimo Caulo, Andrea Soricelli, Paolo Maria Rossini, Joost P.A. Kuijer, Helene Gros-Dagnac, Marco Aiello, and Peter Schönknecht
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Automated segmentation, Hippocampal formation, Audiology, Test (assessment), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Healthy volunteers, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Brain aging, Reliability (statistics)
Published: 2020

17. Progressive phonagnosia in a telephone operator carrying a C9orf72 expansion

Author: Mira Didic, Lucas Ronat, Mathieu Ceccaldi, Olivier Felician, Isabelle Le Ber, Pascal Belin, Eve Tramoni-Negre, Virginia Aglieri, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Otten, Lisa
Subjects: 2019-20 coronavirus outbreak, Cognitive Neuroscience, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Experimental and Cognitive Psychology, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, C9orf72, Network level, medicine, Humans, Dementia, 0501 psychology and cognitive sciences, ComputingMilieux_MISCELLANEOUS, C9orf72 Protein, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Phonagnosia, Operator (linguistics), [SCCO.NEUR] Cognitive science/Neuroscience, Neurodegenerative Diseases, Recognition, Psychology, medicine.disease, Telephone, Phenotype, Neuropsychology and Physiological Psychology, Frontotemporal Dementia, Psychology, Neuroscience, 030217 neurology & neurosurgery, Professional expertise
Abstract: Selectivity is the rule, rather than the exception, in neurodegenerative disease. A retired telephone operator carrying a C9orf72 expansion developed phonagnosia, a selective impairment of voice recognition, contrasting with intact person knowledge and recognition of faces, as a presenting sign of genetically confirmed fronto-temporal dementia. Since the dysfunction in this patient fell into his area of professional expertise, we discuss if overload in voice related neural networks might have caused failure propagating to connected nodes. The interaction with downstream molecular events, triggered by the C9orf72 expansion, may have led to breakdown at the network level, leading to this specific phenotype.
Published: 2020

18. Modular slowing of resting-state dynamic functional connectivity as a marker of cognitive dysfunction induced by sleep deprivation

Author: Diego Lombardo, Jill C. Richardson, Viktor K. Jirsa, Pierre Payoux, Jean-Philippe Ranjeva, Olivier Felician, Mira Didic, Régis Bordet, David Bartrés-Faz, Maxime Guye, Olivier Blin, Demian Battaglia, Catherine Cassé-Perrot, Arnaud Le Troter, Jonathan Wirsich, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de résonance magnétique biologique et médicale (CRMBM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Time Factors, Computer science, Cognitive decline, Resting-state, Visual processing, 0302 clinical medicine, Attention, 0303 health sciences, Functional connectivity, fMRI, 05 social sciences, Brain, Cognition, Memory, Short-Term, Neurology, Visual Perception, medicine.symptom, Adult, Cognitive Neuroscience, Cognitive challenge model, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, Connectome, medicine, Humans, Dementia, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Effects of sleep deprivation on cognitive performance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, Dynamic functional connectivity, Resting state fMRI, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Pattern recognition, Modular design, medicine.disease, Sleep deprivation, Sleep Deprivation, Artificial intelligence, Nerve Net, business, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks.In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks –including Rapid Visual Processing (RVP, assessing sustained visual attention)– and dFC speed quantified at the level of functional subnetworks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module.HighlightsSleep Deprivation (SD) slows down the random walk in FC space implemented by Dynamic Functional Connectivity (dFC) at rest.Whole-brain level slowing of dFC speed does not selectively correlate with fine and taskspecific changes in performanceWe quantify dFC speed separately for different link-based modules coordinated by distinct regional “meta-hubs”Modular dFC speed variations capture subtle and task-specific variations of cognitive performance induced by SD.Author summaryWe interpreted dynamic Functional Connectivity (dFC) as a random walk in the space of possible FC networks performed with a quantifiable “speed”.Here, we analyze a fMRI dataset in which subjects are scanned and cognitively tested both before and after Sleep Deprivation (SD), used as a reversible model of cognitive dysfunction. While global dFC speed slows down after a sleepless night, it is not a sufficiently sensitive metric to correlate with fine and specific cognitive performance changes. To boost the capacity of dFC speed analyses to account for fine and specific cognitive decline, we introduce the notion ofmodular dFC speed. Capitalizing on an edge-centric measure of functional connectivity, which we call Meta-Connectivity, we isolate subgraphs of FC describing relatively independent random walks (dFC modules) and controlled by distinct “puppet masters” (meta-hubs). We then find that variations of the random walk speed of distinct dFC modules now selectively correlate with SD-induced variations of performance in the different tasks. This is in agreement with the fact that different subsystems – distributed but functionally distinct– oversee different tasks.The high sensitivity of modular dFC analyses bear promise of future applications to the early detection and longitudinal characterization of pathologies such as Alzheimer’s disease.
Published: 2020

19. Primary Progressive Aphasia Associated With

Author: Dario, Saracino, Sophie, Ferrieux, Marie, Noguès-Lassiaille, Marion, Houot, Aurélie, Funkiewiez, Leila, Sellami, Vincent, Deramecourt, Florence, Pasquier, Philippe, Couratier, Jérémie, Pariente, Amandine, Géraudie, Stéphane, Epelbaum, David, Wallon, Didier, Hannequin, Olivier, Martinaud, Fabienne, Clot, Agnès, Camuzat, Simona, Bottani, Daisy, Rinaldi, Sophie, Auriacombe, Marie, Sarazin, Mira, Didic, Claire, Boutoleau-Bretonnière, Christel, Thauvin-Robinet, Julien, Lagarde, Carole, Roué-Jagot, François, Sellal, Audrey, Gabelle, Frédérique, Etcharry-Bouyx, Alexandre, Morin, Cinzia, Coppola, Richard, Levy, Bruno, Dubois, Alexis, Brice, Olivier, Colliot, Maria Luisa, Gorno-Tempini, Marc, Teichmann, Raffaella, Migliaccio, Isabelle, Le Ber, and Martine, Vercelletto
Subjects: Male, Tomography, Emission-Computed, Single-Photon, Language Tests, Middle Aged, Neuropsychological Tests, Magnetic Resonance Imaging, Cohort Studies, Aphasia, Primary Progressive, Cross-Sectional Studies, Progranulins, Gene Frequency, Frontotemporal Dementia, Mutation, Humans, Speech, Female, Prospective Studies, Atrophy, Biomarkers, Aged
Abstract: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated withPatients with PPA carryingAmong the 235 patients with PPA, 45 (19%) carriedThis study shows that the most frequent PPA variant associated with
Published: 2020

20. Amygdalar nuclei and hippocampal subfields on MRI

Author: Michela Pievani, Agnese Picco, Jean-Philippe Ranjeva, Giovanni B. Frisoni, Lucilla Parnetti, Piero Floridi, Frederik Barkhof, Jens Wiltfang, Marco Salvatore, Helene Gros-Dagnac, Antonio Ferretti, Julien Sein, Massimo Caulo, Alberto Beltramello, Pierre Payoux, Marco Aiello, Joost P.A. Kuijer, Roberto Tarducci, Tilman Hensch, Renaud Lopes, Björn H. Schott, Peter Schönknecht, Luca Roccatagliata, Camillo Marra, David Bartrés-Faz, Jill C. Richardson, Jorge Jovicich, Flavio Nobili, Antonios Drevelegas, Pieter Jelle Visser, Olivier Blin, Paolo Maria Rossini, Karl Titus Hoffmann, Mira Didic, Régis Bordet, Bernhard W. Müller, Francesca B. Pizzini, Magda Tsolaki, Ute Fiedler, Manos Constantinides, Giulia Quattrini, Moira Marizzoni, Andrea Soricelli, Núria Bargalló, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, IRCCS SDN Napoli, Department of Neuroradiology and Image Research Platform, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institute of Neurology, Queen Square, London, Department of Medicine and Health Sciences, Faculty of Medicine, Universitat de Barcelona and IDIBAPS, Barcelona, Department of Radiology, IRCCS 'Sacro Cuore-Don Calabria', Negrar, Verona, Radiology, Department of Diagnostic and Public Health, University of Verona, Verona, Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Interbalkan Medical Center of Thessaloniki, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neuroradiology Unit, Perugia General Hospital, Perugia, 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], Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Department of Neuroradiology, University Hospital Leipzig, LVR-Hospital Essen, Department for Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, 16132 Genova, Section of Neurology, Department of Medicine, University of Perugia, Perugia, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), IRCCS, Ospedale Policlinico San Martino, Genova, Italy, Department of Health Science (DISSAL), University of Genoa, Genoa, Dept. Neuroscience & Rehabilitation, IRCCS San Raffaele-Pisana, Rome, Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Göttingen, Leibniz Institute for Neurobiology, Magdeburg, Center for Neurodegenerative Diseases (DZNE), Goettingen, Medical Physics Unit, Perugia General Hospital, Perugia, Aristotle University of Thessaloniki, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Netherlands, Maastricht University, Maastricht, Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, German Center for Neurodegenerative Diseases (DZNE), Goettingen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Amsterdam Neuroscience - Brain Imaging, Radiology and nuclear medicine, Neurology, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Trento (UNITN), Università degli studi di Verona = University of Verona (UNIVR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), 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), Leipzig University, Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Leibniz Institute for Neurobiology [Magdeburg] (LIN)
Subjects: Male, STRUCTURAL DIFFERENCES, Neurology, genetic structures, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, FreeSurfer, Medizin, Hippocampus, Hippocampal formation, Amygdalar nuclei, Hippocampal subfields, Multicenter MRI study, Reliability analysis, 0302 clinical medicine, methods [Magnetic Resonance Imaging], hippocampal subfields, multicenter MRI study, reliability analysis, methods [Image Processing, Computer-Assisted], Image Processing, Computer-Assisted, METHODS FREESURFER, ELDERLY-PATIENTS, ComputingMilieux_MISCELLANEOUS, 05 social sciences, Subiculum, BORDERLINE PERSONALITY-DISORDER, Middle Aged, Amygdala, HUMAN BRAIN, Magnetic Resonance Imaging, ALZHEIMERS-DISEASE, standards [Image Processing, Computer-Assisted], Settore MED/26 - NEUROLOGIA, MANUAL SEGMENTATION, medicine.anatomical_structure, Brain size, Cohort, Female, methods [Neuroimaging], Adult, medicine.medical_specialty, Cognitive Neuroscience, anatomy & histology [Hippocampus], Neuroimaging, Cognitive neuroscience, SURFACE-BASED ANALYSIS, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, medicine, Humans, 0501 psychology and cognitive sciences, ddc:610, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, standards [Magnetic Resonance Imaging], business.industry, Reproducibility of Results, SAMPLE-SIZE CALCULATIONS, ddc:616.8, nervous system, anatomy & histology [Amygdala], Nuclear medicine, business, 030217 neurology & neurosurgery, standards [Neuroimaging], Software, FUNCTIONAL-ORGANIZATION
Abstract: Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (epsilon) and spatial overlapping coefficient (DICE) between test and retest session.Results: Significant MRI site and vendor effects (p 0.43, p 0.80).Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.
Published: 2020

21. Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease

Author: Federico Massa, Dario Arnaldi, Bart N.M. van Berckel, Samantha Galluzzi, Rik Ossenkoppele, Eric Guedj, Matteo Grazzini, Marco Pagani, Gianmario Sambuceti, Andrea Chincarini, Cathrine Jonsson, S. Morbelli, Mira Didic, Matteo Bauckneht, Fabrizio De Carli, Patrizia Mecocci, Matteo Pardinia, Alexander Drzezga, Giovanni B. Frisoni, Flavio Nobili, Massimo E. Dottorini, Robert Perneczky, Andrea Brugnolo, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Neurology, VU University medical center, Institute of Bioimaging and Molecular Physiology [Germaneto], National Research Council [Italy] (CNR), Universita degli studi di Genova, Neuroimaging and Telemedicine (LENITEM), IRCCS Fatebenefratelli - Brescia, University Hospital of the Ludwig-Maximilian-University Munich, Medizinische Klinik â€' Innenstadt, Lehrstuhl fÃ¼r Endokrinologie/Diabetologie, Department of Nuclear Medicine [Cologne], University Hospital of Cologne [Cologne], Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), 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), DINOGMI Genoa, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), German Aerospace Center (DLR), Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Clinical Neurophysiology Service, Dept of Endocrinological and Metabolic Sciences, University of Ge, Imperial College London, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Genova = University of Genoa (UniGe), 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), and Università degli Studi di Perugia = University of Perugia (UNIPG)
Subjects: Male, Support Vector Machine, SPM, Volumetric region of interest, Disease, prodromal Alzheimer's disease, pAD, EADC, Image Processing, Computer-Assisted, FDG-PET, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Statistical parametric mapping, General Neuroscience, methods [Positron-Emission Tomography], Brain, Volumetric Region of Interest, General Medicine, Middle Aged, Psychiatry and Mental health, Clinical Psychology, Disease Progression, Female, Radiology, Semi quantitative, medicine.medical_specialty, Head to head, European Alzheimer Disease Consortium, Prodromal Symptoms, macromolecular substances, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, statistical parametric mapping, Alzheimer Disease, Fluorodeoxyglucose F18, medicine, Humans, ddc:610, diagnostic imaging [Brain], Aged, Neuroscience (all), business.industry, prodromal Alzheimer’s disease, [SCCO.NEUR]Cognitive science/Neuroscience, Prodromal Alzheimer's disease, carbohydrates (lipids), Early Diagnosis, Head-to-head comparison, Positron-Emission Tomography, head-to-head comparison, volumetric region of interest, Geriatrics and Gerontology, business, European Alzheimer Disease Consortium, FDG-PET, head-to-head comparison, prodromal Alzheimer's disease, statistical parametric mapping, volumetric region of interest, Neuroscience (all), Clinical Psychology, Geriatrics and Gerontology, Psychiatry and Mental Health, diagnostic imaging [Alzheimer Disease], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [ 18 ]F-FDG-PET. Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. Methods: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [ 18 ]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). Results: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. Conclusion: The study confirms the good accuracy of [ 18 ]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.
Published: 2020

22. A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment

Author: Sven, Joubert, Ludovic, Gardy, Mira, Didic, Isabelle, Rouleau, and Emmanuel J, Barbeau
Subjects: Memory Disorders, Alzheimer Disease, Memory, Humans, Cognitive Dysfunction, Neuropsychological Tests, Semantics
Abstract: Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.
Published: 2020

23. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

Author: Jean-Philippe Ranjeva, Frederik Barkhof, Jorge Jovicich, Régis Bordet, Jill C. Richardson, Elena Rolandi, Magda Tsolaki, Andrea Soricelli, Olivier Blin, Lucilla Parnetti, Marco Salvatore, Claudio Babiloni, Tilman Hensch, Jens Wiltfang, Camillo Marra, José Luis Molinuevo, Libera Cavaliere, Samantha Galluzzi, Moira Marizzoni, Diego Albani, Mira Didic, Clarissa Ferrari, Flavio Nobili, Federica Fusco, Paolo Maria Rossini, Giovanni B. Frisoni, Gianluigi Forloni, Federica Ribaldi, Pierre Payoux, Pieter Jelle Visser, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Department of Physiology and Pharmacology 'Vittorio Erspamer', Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Neuroscience Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institutes of Neurology and Healthcare Engineering, UCL, London, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, Department of Gerontology, Neurosciences & Orthopedics, Catholic University, Rome, Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Section of Neurology, Centre for Memory Disturbances, University of Perugia, 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], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Area Neuroscience, IRCCS San Raffaele, Rome, IRCCS SDN Napoli, Department of Neurology (Aristotle University of Thessaloniki), Aristotle University of Thessaloniki, Alzheimer Center Amsterdam, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leipzig University, Università degli Studi di Trento (UNITN), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), 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)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Lille Neurosciences & Cognition - U 1172 (LilNCog)
Subjects: Male, 0301 basic medicine, Oncology, Apolipoprotein E, Aging, Medizin, Cohort Studies, 0302 clinical medicine, Cerebrospinal fluid, Cutoff, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, General Neuroscience, Alzheimer's disease, 3. Good health, Settore MED/26 - NEUROLOGIA, Biomarker (medicine), Female, Heterozygote, medicine.medical_specialty, CSF cutoff, Disease progression, Mild cognitive impairment, Tau protein, tau Proteins, 03 medical and health sciences, Apolipoproteins E, Neuroimaging, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, medicine.disease, Peptide Fragments, ddc:616.8, 030104 developmental biology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The Aβ42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOEε4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEε4+, lower cutoff for APOEε4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single Aβ42 and Aβ42/P-tau cutoffs. APOEε4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis.
Published: 2020

24. Dynamic Functional Connectivity as a complex random walk: Definitions and the dFCwalk toolbox

Author: Diego Lombardo, Viktor K. Jirsa, Lucas Arbabyazd, Olivier Blin, Mira Didic, Demian Battaglia, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Computer science, Clinical Biochemistry, Neuroimaging, 010501 environmental sciences, 01 natural sciences, Functional Connectivity, 03 medical and health sciences, Decomposition (computer science), lcsh:Science, Scaling, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, Dynamic functional connectivity, 0303 health sciences, dFC random walk analyses, Resting state fMRI, [SCCO.NEUR]Cognitive science/Neuroscience, fMRI, Process (computing), Control reconfiguration, Method Article, Random walk, Medical Laboratory Technology, Distribution (mathematics), Chronnectome, lcsh:Q, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Algorithm
Abstract: • We have developed a framework to describe the dynamics of Functional Connectivity (dFC) estimated from brain activity time-series as a complex random walk in the space of possible functional networks. This conceptual and methodological framework considers dFC as a smooth reconfiguration process, combining “liquid” and “coordinated” aspects. Unlike other previous approaches, our method does not require the explicit extraction of discrete connectivity states. • In our previous work, we introduced several metrics for the quantitative characterization of the dFC random walk. First, dFC speed analyses extract the distribution of the time-resolved rate of reconfiguration of FC along time. These distributions have a clear peak (typical dFC speed, that can already serve as a biomarker) and fat tails (denoting deviations from Gaussianity that can be detected by suitable scaling analyses of FC network streams). Second, meta-connectivity (MC) analyses identify groups of functional links whose fluctuations co-vary in time and that define veritable dFC modules organized along specific dFC meta-hub controllers (differing from conventional FC modules and hubs). The decomposition of whole-brain dFC by MC allows performing dFC speed analyses separately for each of the detected dFC modules. • We present here blocks and pipelines for dFC random walk analyses that are made easily available through a dedicated MATLABⓇ toolbox (dFCwalk), openly downloadable. Although we applied such analyses mostly to fMRI resting state data, in principle our methods can be extended to any type of neural activity (from Local Field Potentials to EEG, MEG, fNIRS, etc.) or even non-neural time-series., Graphical abstract Image, graphical abstract
Published: 2020

25. The frequency and influence of dementia risk factors in prodromal Alzheimer's disease

Author: Alexandre de Mendonça, Gerald Novak, Giovanni B. Frisoni, Philip Scheltens, Harald Hampel, Hilkka Soininen, Silvia Morbelli, Peter Johannsen, Alberto Lleó, Myriam Alexander, Ellis Niemantsverdriet, Mark Forrest Gordon, Solène Dauby, Mira Didic, Samantha Galluzzi, Angelika Wientzek, Rik Vandenberghe, Isabel Santana, Frans R.J. Verhey, Isabelle Bos, Yvonne Freund-Levi, Sebastiaan Engelborghs, Stephanie J.B. Vos, Alexander Drzezga, Wolfgang Maier, Johannes Kornhuber, Pieter Jelle Visser, Daniel Alcolea, Ellen Elisa De Roeck, Dina Silva, Inês Baldeiras, Jens Wiltfang, Oliver Peters, Anders Wallin, Eric Salmon, Sanna-Kaisa Herukka, E. Rüther, Magda Tsolaki, Preciosa M. Coloma, Christine Bastin, Lutz Frölich, Bart N.M. van Berckel, Åsa K. Wallin, Arto Nordlund, Flavio Nobili, Alzheimer's Disease Neuroimaging Initiative, Clinical sciences, Neurology, Educational Science, Faculty of Psychology and Educational Sciences, Maastricht University [Maastricht], Universität Heidelberg [Heidelberg] = Heidelberg University, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Georg-August-University = Georg-August-Universität Göttingen, Universität Bonn = University of Bonn, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Aristotle University of Thessaloniki, Karolinska Institutet [Stockholm], Copenhagen University Hospital, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hospital de la Santa Creu i Sant Pau, Université de Genève = University of Geneva (UNIGE), Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli studi di Genova = University of Genoa (UniGe), University of Cologne, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), VU University Medical Center [Amsterdam], Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, Centro Hospitalar e Universitário [Coimbra], Université de Lisbonne, University of Gothenburg (GU), F. Hoffmann-La Roche [Basel], Roche Products Ltd, Janssen Research & Development, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Lund University [Lund], CHU Pitié-Salpêtrière [AP-HP], 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)-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), University of Eastern Finland, Repositório da Universidade de Lisboa, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), and School of Medicine / Clinical Medicine
Subjects: cognition, Male, Aging, MILD COGNITIVE IMPAIRMENT, ALCOHOL-CONSUMPTION, etiology [Alzheimer Disease], Disease, GUIDELINES, etiology [Cognitive Dysfunction], Alcohol Drinking/adverse effects, ddc:616.89, Cognition, 0302 clinical medicine, Cognitive decline, 10. No inequality, Alzheimer Disease/etiology, Depression (differential diagnoses), Medicine(all), Depression, General Neuroscience, Alzheimer's disease, Biomarkers, IWG-2 criteria, NIA-AA criteria, Prognosis, Risk factors, Neuroscience (all), Developmental Biology, Geriatrics and Gerontology, Neurology (clinical), ASSOCIATION, Middle Aged, CEREBROSPINAL-FLUID BIOMARKERS, 3. Good health, PREVALENCE, adverse effects [Alcohol Drinking], OBESITY, depression, Disease Progression, Female, Risk assessment, Psychology, medicine.medical_specialty, Alcohol Drinking, Hypercholesterolemia, DIAGNOSIS, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, Dementia, Cognitive Dysfunction, Cognitive Dysfunction/etiology, ddc:610, Obesity, Effects of sleep deprivation on cognitive performance, Psychiatry, METAANALYSIS, Aged, Proportional Hazards Models, DECLINE, 030214 geriatrics, Proportional hazards model, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, VASCULAR RISK, Human medicine, 030217 neurology & neurosurgery
Abstract: We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD., final draft, peerReviewed
Published: 2017

26. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease

Author: Anne-Laure Aziz, Jean-Philippe Ranjeva, Eric Guedj, José Boucraut, Lejla Koric, Lauréline Duprat, Olivier Felician, Sven Joubert, Bernard Giusiano, Mathieu Ceccaldi, Mira Didic, Claude Gueriot, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche de l'Institut universitaire de gériatrie, Université de Montréal (UdeM), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre de Mémoire de Ressources et de Recherche [Hôpital La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE)-CHU Marseille, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Mémoire de Ressources et de Recherche, CHU Marseille, and Guedj, Eric
Subjects: Male, 0301 basic medicine, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Disease, Neuroimaging biomarkers, Severity of Illness Index, Cognition, 0302 clinical medicine, Semantic memory, Early-onset Alzheimer's disease, Age of Onset, Aged, 80 and over, General Neuroscience, Neurodegeneration, Brain, Middle Aged, Alzheimer's disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Amyloid, medicine.medical_specialty, Temporoparietal junction, Neuroimaging, 03 medical and health sciences, Atrophy, Alzheimer Disease, Memory, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], snc, Positron emission tomography imaging, Aged, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Glucose, 030104 developmental biology, Positron-Emission Tomography, Posterior cingulate, Nerve Degeneration, Neurology (clinical), Geriatrics and Gerontology, Age of onset, Neuroscience, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.
Published: 2017

27. The repeatability of cognitive performance: a meta-analysis

Author: Peter M. Kappeler, E. A. Smith, Shinichi Nakagawa, J. Henke-von der Malsburg, P. K. Y. Chow, S. Klein, Alexis S. Chaine, Blandine Doligez, Hanne Løvlie, Mathieux Lihoreau, Julie Morand-Ferron, Enrico Sorato, Emmanuel Barbeau, Lisa J. Wallis, Gladys Barragan-Jason, Franziska Huebner, Mark A. Whiteside, Susann Oesterwind, Stephen E. G. Lea, Sarah Dalesman, Anna V. Wilkinson, Claudia Fichtel, Louis D. Matzel, Bruno Sauce, Séverine D. Buechel, Annika Boussard, Amélie Cabirol, Sabine Tebbich, Joël Fagot, Christian Nawroth, Jean-Marc Devaud, J. O. van Horik, Mira Didic, Cristina M. Atance, Pierre Bize, E. Hermer, Ludwig Huber, Jan Langbein, Nicolas Claidière, Laure Cauchard, Ellis J. G. Langley, Maxime Cauchoix, Station d'écologie théorique et expérimentale (SETE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Study in Toulouse (IAST), Centre for Research in Animal Behaviour, Psychology, University of Exeter, Hokkaido University [Sapporo, Japan], University of Ottawa [Ottawa], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), School of Biological Sciences [Aberdeen], University of Aberdeen, Stockholm University, Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Montréal (UdeM), Laboratoire de psychologie cognitive (LPC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aberystwyth University, 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), Evolution, adaptation et comportement, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University [Göttingen], Leibniz Institute for Farm Animal Biology (FBN), Linköping University (LIU), Rutgers University System (Rutgers), University of New South Wales [Sydney] (UNSW), University of Rostock, University of Lincoln, University of Vienna [Vienna], Eötvös Loránd University (ELTE), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University = Georg-August-Universität Göttingen, ANR-10-LABX-0041,TULIP,Towards a Unified theory of biotic Interactions: the roLe of environmental(2010), Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de neurosciences cognitives de la méditerranée - UMR 6193 (INCM), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Ecology and Evolution, Université de Lausanne (UNIL), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, cognition, evolution Keywords: cognitive repeatability, Context (language use), evolutionary biology of cognition, 010603 evolutionary biology, 01 natural sciences, Subject Areas: behaviour, General Biochemistry, Genetics and Molecular Biology, Task (project management), memory, [SCCO]Cognitive science, Animals, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, Effects of sleep deprivation on cognitive performance, Biological sciences, individual differences, ComputingMilieux_MISCELLANEOUS, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Biological Variation, Individual, learning, Behavior, Animal, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, 05 social sciences, C182 Evolution, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognition, Repeatability, Articles, C120 Behavioural Biology, attention, Variation (linguistics), Meta-analysis, [SCCO.PSYC]Cognitive science/Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Agricultural and Biological Sciences, Psychology, Cognitive psychology
Abstract: Behavioural and cognitive processes play important roles in mediating an individual's interactions with its environment. Yet, while there is a vast literature on repeatable individual differences in behaviour, relatively little is known about the repeatability of cognitive performance. To further our understanding of the evolution of cognition, we gathered 44 studies on individual performance of 25 species across six animal classes and used meta-analysis to assess whether cognitive performance is repeatable. We compared repeatability ( R ) in performance (1) on the same task presented at different times (temporal repeatability), and (2) on different tasks that measured the same putative cognitive ability (contextual repeatability). We also addressed whether R estimates were influenced by seven extrinsic factors (moderators): type of cognitive performance measurement, type of cognitive task, delay between tests, origin of the subjects, experimental context, taxonomic class and publication status. We found support for both temporal and contextual repeatability of cognitive performance, with mean R estimates ranging between 0.15 and 0.28. Repeatability estimates were mostly influenced by the type of cognitive performance measures and publication status. Our findings highlight the widespread occurrence of consistent inter-individual variation in cognition across a range of taxa which, like behaviour, may be associated with fitness outcomes. This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Published: 2019

28. Two-year longitudinal monitoring of amnestic mild cognitive impairment patients with prodromal Alzheimer's disease using topographical biomarkers derived from functional magnetic resonance imaging and electroencephalographic activity

Author: Jill C. Richardson, Flavio Nobili, Libera Cavaliere, Moira Marizzoni, Claudio Babiloni, Gianluigi Forloni, Giovanni B. Frisoniand, Mira Didic, Régis Bordet, Ludovico Minati, Jorge Jovicich, Susanna Lopez, Marco Salvatore, Jens Wiltfang, David Bartrés Faz, Claudio Del Percio, Camillo Marra, Giuseppe Noce, Andrea Soricelli, Diego Albani, Clarissa Ferrari, Tilman Hensch, Lucilla Parnetti, José Luis Molinuevo, Olivier Blin, Pierre Payoux, Cinzia Costa, Peter Schönknecht, Roberta Lizio, Pieter Jelle Visser, Magda Tsolaki, Lucia Farotti, Paolo Maria Rossini, Samantha Galluzzi, Ute Fiedler, Daniele Orlandi, Davide V. Moretti, University of Trento [Trento], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), IRCCS SDN Napoli, IRCCS Istituto Nazionale dei Tumori [Milano], Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Universität Leipzig, Pasqual Maragall Foundation, Universitat de Barcelona (UB), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Aristotle University of Thessaloniki, VU University Medical Center [Amsterdam], GlaxoSmithKline, Glaxo Smith Kline, Université de Lille, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), Universität Duisburg-Essen [Essen], Universität Leipzig [Leipzig], 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), Université Fédérale Toulouse Midi-Pyrénées, University of Duisburg-Essen, Otten, Lisa, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: 0301 basic medicine, Male, pharma cog project, Medizin, Prodromal Alzheimer's Disease, Electroencephalography, Audiology, Neuropsychological Tests, Amnesic Mild Cognitive Impairment (aMCI), 0302 clinical medicine, PharmaCog project, Alpha rhythms, prodromal alzheimer’s disease, Longitudinal Studies, Default mode network, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, General Neuroscience, Brain, clinical trial, General Medicine, Middle Aged, Magnetic Resonance Imaging, Clinical Trial, Psychiatry and Mental health, Clinical Psychology, Settore MED/26 - NEUROLOGIA, Resting State, alpha rhythms, amnesic mild cognitive impairment, biomarkers, electroencephalography, functional magnetic resonance imaging, oddball event-related potentials, resting state, Functional Magnetic Resonance Imaging (fMRI), Disease Progression, Evoked Potentials, Auditory, Female, prodromal Alzheimer’s disease, medicine.medical_specialty, Posterior parietal cortex, 03 medical and health sciences, Alzheimer Disease, medicine, Dementia, Humans, Cognitive Dysfunction, Electroencephalography (EEG), Aged, prodromal Alzheimer's disease, Resting state fMRI, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, medicine.disease, Cortex (botany), 030104 developmental biology, Posterior cingulate, Amnesia, Geriatrics and Gerontology, Functional magnetic resonance imaging, business, 030217 neurology & neurosurgery, Oddball Event-Related Potentials (ERPs), Biomarkers
Abstract: Auditory "oddball" event-related potentials (aoERPs), resting state functional magnetic resonance imaging (rsfMRI) connectivity, and electroencephalographic (rsEEG) rhythms were tested as longitudinal functional biomarkers of prodromal Alzheimer's disease (AD). Data were collected at baseline and four follow-ups at 6, 12, 18, and 24 months in amnesic mild cognitive impairment (aMCI) patients classified in two groups: "positive" (i.e., "prodromal AD" n=81) or "negative" (n=63) based on a diagnostic marker of AD derived from cerebrospinal samples (Aβ 42 /P-tau ratio). A linear mixed model design was used to test functional biomarkers for Group, Time, and Group×Time effects adjusted by nuisance covariates (only data until conversion to dementia was used). Functional biomarkers that showed significant Group effects ("positive" versus "negative", p
Published: 2019

29. Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC)

Author: Giovanni B. Frisoni, Eric Guedj, Javier Arbizu, Massimo E. Dottorini, Justine Hugon, Patrizia Mecocci, Miguel Castelo-Branco, Sebastiaan Engelborghs, Carlo Ferrarese, Isabel Santana, Flavio Nobili, Andrea Chincarini, Matteo Bauckneht, M Queneau, E Peira, Mira Didic, Jeroen Verhaeghe, Mario Riverol, A. de Mendonça, Lucrezia Hausner, Valentina Garibotto, Matteo Pardini, Monica Musarra, Ugo Paolo Guerra, Silvia Morbelli, K A Büsing, Hospitais da Universidade de Coimbra (H.U.C.), University of Coimbra [Portugal] (UC), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Perugia (UNIPG), Repositório da Universidade de Lisboa, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), and Università degli Studi di Perugia = University of Perugia (UNIPG)
Subjects: Fluorine Radioisotopes/metabolism, Male, Fluorine Radioisotopes, Amyloid pet, Plaque, Amyloid, Disease, Audiology, lcsh:RC346-429, Cohort Studies, 0302 clinical medicine, Visual assessment, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, 05 social sciences, Brain, Regular Article, Middle Aged, Europe, Neurology, lcsh:R858-859.7, Female, medicine.symptom, Semi quantitative, Adult, medicine.medical_specialty, Cognitive Neuroscience, Alzheimer Disease/diagnostic imaging, Population, Standardized uptake value, lcsh:Computer applications to medicine. Medical informatics, Amyloid PET, Semi-quantification, Visual assessment, Semi-quantification, Asymptomatic, ddc:616.0757, 050105 experimental psychology, Europe/epidemiology, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, education, Biology, Grading (tumors), lcsh:Neurology. Diseases of the nervous system, Aged, Retrospective Studies, Plaque, Amyloid/diagnostic imaging, business.industry, Amyloid PET, Brain/diagnostic imaging, Positron-Emission Tomography/methods, Positron-Emission Tomography, Human medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/), Background: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. Methods: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. Conclusion: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale., V.G. was supported by the Swiss National Science Foundation (under grant SNF 320030_169876) and by the Velux Stiftung (project n. 1123). E.P. was supported by Airalzh Onlus – COOP Italia (grant number 138812/Rep n° 2459).
Published: 2019

30. Biomarker matrix to track short term disease progression in amnestic mild cognitive impairment patients with prodromal Alzheimer's disease

Author: Ulrich Hegerl, Gianluigi Forloni, Paolo Maria Rossini, Andrea Soricelli, Jill C. Richardson, Francesca B. Pizzini, Diego Albani, Ambra Macis, Magda Tsolaki, Mira Didic, Giovanni B. Frisoni, Jorge Jovicich, Lucilla Parnetti, Marco Salvatore, Pierre Payoux, Régis Bordet, Flavio Nobili, Pieter Jelle Visser, Libera Cavaliere, Clarissa Ferrari, Jens Wiltfang, Tilman Hensch, José Luis Molinuevo, Moira Marizzoni, Claudio Babiloni, Olivier Blin, Samantha Galluzzi, Karl-Titus Hoffmann, Claudio Del Percio, Peter Schönknecht, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: 0301 basic medicine, Oncology, Male, Medizin, Neuropsychological Tests, ddc:616.89, biomarker matrices, 0302 clinical medicine, magnetic resonance imaging, Longitudinal Studies, Cognitive decline, Alzheimer's disease, clinical trial, mild cognitive impairment, General Neuroscience, Brain, General Medicine, Human brain, Middle Aged, Clinical trial, Psychiatry and Mental health, Clinical Psychology, medicine.anatomical_structure, Biomarker matrices, Disease Progression, Biomarker (medicine), Female, Alzheimer’s disease, medicine.medical_specialty, tau Proteins, Alzheimer’s disease, biomarker matrices, clinical trial, magnetic resonance imaging, mild cognitive impairment, 03 medical and health sciences, Atrophy, Magnetic resonance imaging, Alzheimer Disease, Internal medicine, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Aged, Amyloid beta-Peptides, Resting state fMRI, business.industry, Dentate gyrus, Mild cognitive impairment, medicine.disease, Peptide Fragments, 030104 developmental biology, Positron-Emission Tomography, Amnesia, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Background: Assessment of human brain atrophy in temporal regions using magnetic resonance imaging (MRI), resting state functional MRI connectivity in the left parietal cortex, and limbic electroencephalographic (rsEEG) rhythms as well as plasma amyloid peptide 42 (Aβ 42 ) has shown that each is a promising biomarker of disease progression in amnestic mild cognitive impairment (aMCI) patients with prodromal Alzheimer's disease (AD). However, the value of their combined use is unknown. Objective: To evaluate the association with cognitive decline and the effect on sample size calculation when using a biomarker composite matrix in prodromal AD clinical trials. Methods: Multicenter longitudinal study with follow-up of 2 years or until development of incident dementia. APOE ϵ4-specific cerebrospinal fluid (CSF) Aβ 42 /P-tau cut-offs were used to identify aMCI with prodromal AD. Linear mixed models were performed 1) with repeated matrix values and time as factors to explain the longitudinal changes in ADAS-cog13, 2) with CSF Aβ 42 /P-tau status, time, and CSF Aβ 42 /P-tau status×time interaction as factors to explain the longitudinal changes in matrix measures, and 3) to compute sample size estimation for a trial implemented with the selected matrices. Results: The best composite matrix included the MRI volumes of hippocampal dentate gyrus and lateral ventricle. This matrix showed the best sensitivity to track disease progression and required a sample size 31% lower than that of the best individual biomarker (i.e., volume of hippocampal dentate gyrus). Conclusion: Optimal matrices improved the statistical power to track disease development and to measure clinical progression in the short-term period. This might contribute to optimize the design of future clinical trials in MCI.
Published: 2019

31. Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques

Author: Rocco Marchitelli, Piero Floridi, Agnese Picco, Mira Didic, Manos Constantinidis, Julien Sein, Franco Alessandrini, Bernhard W. Müller, Carlo Cavaliere, Olivier Blin, Tilman Hensch, Lucilla Parnetti, Jean-Philippe Ranjeva, Antonios Drevelegas, Frederik Barkhof, Pierre Payoux, Roberto Tarducci, Jens Wiltfang, Beatriz Bosch, Magda Tsolaki, Camillo Marra, Régis Bordet, Renaud Lopes, Stéphanie Bombois, Massimo Caulo, Jorge Jovicich, Andrea Soricelli, Pieter Jelle Visser, David Bartrés-Faz, Antonio Ferretti, Núria Bargalló, Joost P.A. Kuijer, Karl-Titus Hoffmann, Moira Marizzoni, Luca Roccatagliata, Ludovico Minati, Giada Zoccatelli, Ute Fiedler, Alberto Beltramello, Helene Gros-Dagnac, Marco Aiello, Peter Schönknecht, Paolo Maria Rossini, Giovanni B. Frisoni, and Flavio Nobili
Subjects: medicine.medical_specialty, Pathology, Reproducibility, Radiological and Ultrasound Technology, Resting state fMRI, 05 social sciences, Regression analysis, Audiology, Brain mapping, 050105 experimental psychology, Regression, 03 medical and health sciences, Communication noise, 0302 clinical medicine, Neurology, medicine, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Psychology, 030217 neurology & neurosurgery, Reliability (statistics), Default mode network
Abstract: Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.
Published: 2016

32. P3‐368: PREDICTING AND MONITORING SHORT‐TERM DISEASE PROGRESSION IN A‐MCI PATIENTS WITH PRODROMAL AD USING MRI STRUCTURAL BRAIN BIOMARKERS

Author: Pierre Payoux, Giovanni B. Frisoni, Andrea Soricelli, Libera Cavaliere, Jill C. Richardson, Jorge Jovicich, Pieter Jelle Visser, Jens Wiltfang, Gianluigi Forloni, Clarissa Ferrari, Régis Bordet, Flavio Nobili, Magda Tsolaki, Lucilla Parnetti, Federica Ribaldi, Paolo Maria Rossini, Peter Schönknecht, Moira Marizzoni, Mira Didic, Olivier Blin, and José Luis Molinuevo
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease progression, Term (time), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2018

33. P4‐077: BLOOD INFLAMMATORY PROFILES MEASURED BY THE ADFLAG ® TEST ENABLE STRATIFICATION OF PRE‐DEMENTIA ALZHEIMER'S DISEASE

Author: Nathalie Compagnone, Moira Marizzoni, Samantha Galluzzi, Andrea Soricelli, Laura Lanteaume, Beatrice Blanc, Jorge Jovicich, Diego Albani, David Bartes-Faz, Joelle Micaleff, Gianluigi Forloni, Ute Fiedler, Pierre Payoux, Magda Tsolaki, Régis Bordet, Olivier Blin, Flavio Nobili, Pieter Jelle Visser, Pauline Picamal, Lucilla Parnetti, Peter Schönknecht, Jill C. Richardson, Mira Didic, Giovanni B. Frisoni, and Paolo Maria Rossini
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Stratification (water), Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2018

34. IC‐P‐126: VOLUMETRIC ACCURACY OF A FULLY AUTOMATIC TOOL FOR WHITE MATTER HYPERINTENSITIES (WMHS) SEGMENTATION

Author: Mira Didic, Tilman Hensch, Agnese Picco, Moira Marizzoni, Ute Fiedler, Stéphanie Bombois, Antonio Ferretti, Jean-Philippe Ranjeva, Robertto Tarducci, Frederik Barkhof, Camillo Marra, Federica Ribaldi, Jorge Jovicich, Joost P.A. Kuijer, Renaud Lopes, Alberto Beltramello, Antonios Drevelegas, Luca Roccatagliata, Giovanni B. Frisoni, Helene Gros-Dagnac, Carlo Cavaliere, David Bartrés-Faz, Marco Aiello, Julien Sein, Peter Schönknecht, Lucilla Parnetti, Andrea Soricelli, Clarissa Ferrari, Flavio Nobili, Karl-Titus Hoffmann, Paolo Maria Rossini, Manos Constantinides, Beatriz Bosch, Magda Tsolaki, Jens Wiltfang, Martina Montalti, Núria Bargalló, Régis Bordet, Bernhard W. Müller, Olivier Blin, Piero Floridi, Franco Alessandrini, Pierre Payoux, Pieter Jelle Visser, and Massimo Caulo
Subjects: Epidemiology, business.industry, Computer science, Health Policy, Pattern recognition, Hyperintensity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Fully automatic, Segmentation, Neurology (clinical), Artificial intelligence, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Published: 2018

35. Novel VCP mutations expand the mutational spectrum of frontotemporal dementia

Author: Didier Hannequin, Agnès Camuzat, Yassaman Ghassab, Isabelle David, Sylvie Forlani, Morwena Latouche, Dario Saracino, Eric Le Guern, Lena Guillot-Noel, Cinzia Coppola, Mira Didic, Daisy Rinaldi, Vincent Anquetil, Lucie Guyant-Maréchal, Alexis Brice, Ftd-Als, Fabienne Clot, Giuseppe Di Iorio, Isabelle Le Ber, 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), Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania 'Luigi Vanvitelli', Naples, Italy, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Otten, Lisa, Saracino, Dario, Clot, Fabienne, Camuzat, Agnè, Anquetil, Vincent, Hannequin, Didier, Guyant-Maréchal, Lucie, Didic, Mira, Guillot-Noël, Léna, Rinaldi, Daisy, Latouche, Morwena, Forlani, Sylvie, Ghassab, Yassaman, Coppola, Cinzia, Di Iorio, Giuseppe, David, Isabelle, Le Guern, Eric, Brice, Alexi, Le Ber, Isabelle, CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Aging, Valosin-containing protein, Mutation, Missense, Frontotemporal lobar degeneration, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Valosin Containing Protein, medicine, Dementia, Humans, Amyotrophic lateral sclerosis, Gene, Amyotrophic lateral sclerosi, ComputingMilieux_MISCELLANEOUS, Aged, Genetics, Mutation, biology, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, TAR DNA binding protein 43, Middle Aged, medicine.disease, Pedigree, 030104 developmental biology, Paget's disease of bone, Frontotemporal Dementia, biology.protein, Neurology (clinical), Geriatrics and Gerontology, 030217 neurology & neurosurgery, Developmental Biology, Frontotemporal dementia
Abstract: Valosin-containing protein (VCP) mutations are rare causes of autosomal dominant frontotemporal dementias associated with Paget's disease of bone, inclusion body myopathy, and amyotrophic lateral sclerosis. We analyzed the VCP gene in a cohort of 199 patients with frontotemporal dementia and identified 7 heterozygous mutations in unrelated families, including 3 novel mutations segregating with dementia. This expands the VCP mutation spectrum and suggests that although VCP mutations are rare (3.5% in this study), the gene should be analyzed even in absence of the full syndromic complex. Reporting genetic variants with convincing arguments for pathogenicity is important considering the large amount of data generated by next-generation sequencing and the growing difficulties to interpret rare genetic variants identified in isolated cases.
Published: 2018

36. Association between Gray Matter alterations and CSF biomarkers in amnestic MCI patients

Author: Zacà, Domenico, Giari, Giuliano, Moira, Marizzoni, Clarissa, Ferrari, Samantha, Galluzzi, Diego, Albani, Claudio, Babiloni, Mira, Didic, Josè Luis Molinuevo, Flavio Mariano Nobili, Lucilla, Parnetti, Pierre, Payoux, Paolo Maria Rossini, Peter, Schönknecht, Andrea, Soricelli, Magda, Tsolaki, Pieter Jelle Visser, Jens, Wiltfang, Regis, Bordet, Libera, Cavaliere, Jill, Richardson, Olivier, Blin, Frisoni, Giovanni B., and Jovicich, Jorge
Published: 2018

37. Longitudinal reproducibility of automatically segmented hippocampal subfields: A multisite European 3T study on healthy elderly

Author: Agnese Picco, Stéphanie Bombois, Nicola Salvadori, Lucilla Parnetti, Helene Gros-Dagnac, Mira Didic, Régis Bordet, Manos Constantinidis, Jorge Jovicich, Antonio Ferretti, Renaud Lopes, Jean-Philippe Ranjeva, Frederik Barkhof, Beatriz Bosch, Luca Roccatagliata, Magda Tsolaki, Giada Zoccatelli, Alberto Beltramello, Marco Aiello, Antonios Drevelegas, David Bartrés-Faz, Peter Schönknecht, Flavio Nobili, Andrea Soricelli, Camillo Marra, Julien Sein, Luigi Antelmi, Tilman Hensch, Ute Fiedler, Núria Bargalló, Bernhard W. Müller, Massimo Caulo, Giovanni B. Frisoni, Paolo Maria Rossini, Jens Wiltfang, Carlo Cavaliere, Moira Marizzoni, Pierre Payoux, Roberto Tarducci, Pieter Jelle Visser, Karl-Titus Hoffmann, Olivier Blin, Piero Floridi, Joost P.A. Kuijer, and Franco Alessandrini
Subjects: Reproducibility, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Subiculum, Hippocampus, Magnetic resonance imaging, Context (language use), Hippocampal formation, medicine.anatomical_structure, nervous system, Neurology, Gyrus, Hippocampal Fissure, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Nuclear medicine, business, Psychology, Neuroscience
Abstract: Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE
Published: 2015

38. [P3–062]: ACROSS‐SESSION REPRODUCIBILITY OF AUTOMATIC WHITE MATTER HYPERINTENSITIES SEGMENTATION: A EUROPEAN MULTI‐SITE 3T STUDY

Author: Federica Ribaldi, Moira Marizzoni, Jorge Jovicich, Clarissa Ferrari, Beatriz Bosch, David Bartrés‐Faz, Bernhard W. Müller, Jens Wiltfang, Ute Fiedler, Luca Roccatagliata, Agnese Picco, Flavio Nobili, Olivier Blin, Stephanie Bombois, Renaud Lopes, Regis Bordet, Julien Sein, Jean‐Philippe Ranjeva, Mira Didic, Helene Gros‐Dagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, Núria Bargallo, Antonio Ferretti, Massimo Caulo, Marco Aiello, Carlo Cavaliere, Andrea Soricelli, Lucilla Parnetti, Robertto Tarducci, Piero Floridi, Magda Tsolaki, Manos Constantinides, Antonios Drevelegas, Paolo Maria Rossini, Camillo Marra, Peter Schonknecht, Tilman Hensch, Karl‐Titus Hoffmann, Joost Kuijer, Pieter Jelle Visser, Frederik Barkhof, and Giovanni B. Frisoni
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2017

39. [P4–157]: CSF BIOMARKERS AND EFFECT OF APOLIPOPROTEIN E GENOTYPE, AGE AND SEX ON CUT‐OFF DERIVATION IN MILD COGNITIVE IMPAIRMENT

Author: Pierre Payoux, Moira Marizzoni, Jens Wiltfang, Andrea Soricelli, Pieter Jelle Visser, José Luis Molinuevo, Magda Tsolaki, Paolo Maria Rossini, Claudio Babiloni, Giovanni B. Frisoni, Libera Cavaliere, Jill C. Richardson, Lucilla Parnetti, Régis Bordet, Peter Schönknecht, Clarissa Ferrari, Diego Albani, Samantha Galluzzi, Olivier Blin, Flavio Nobili, Mira Didic, Jorge Jovicich, and Gianluigi Forloni
Subjects: 0301 basic medicine, Apolipoprotein E, Epidemiology, business.industry, Health Policy, Physiology, Age and sex, Developmental psychology, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Csf biomarkers, Medicine, Neurology (clinical), Derivation, Geriatrics and Gerontology, Cognitive impairment, business, 030217 neurology & neurosurgery
Published: 2017

40. [IC‐P‐167]: ACROSS‐SESSION REPRODUCIBILITY OF AUTOMATIC WHITE MATTER HYPERINTENSITIES SEGMENTATION: A EUROPEAN MULTI‐SITE 3T STUDY

Author: Jean-Philippe Ranjeva, Frederik Barkhof, Piero Floridi, Manos Constantinides, Moira Marizzoni, Massimo Caulo, Agnese Picco, Franco Alessandrini, Jorge Jovicich, Antonio Ferretti, Antonios Drevelegas, Régis Bordet, Mira Didic, Paolo Maria Rossini, Andrea Soricelli, Giada Zoccatelli, Pierre Payoux, Lucilla Parnetti, Beatriz Bosch, Magda Tsolaki, Bernhard W. Müller, Giovanni B. Frisoni, Renaud Lopes, Luca Roccatagliata, Jens Wiltfang, Clarissa Ferrari, David Bartrés-Faz, Pieter Jelle Visser, Flavio Nobili, Julien Sein, Helene Gros-Dagnac, Federica Ribaldi, Olivier Blin, Stéphanie Bombois, Tilman Hensch, Camillo Marra, Marco Aiello, Núria Bargalló, Carlo Cavaliere, Peter Schönknecht, Robertto Tarducci, Karl-Titus Hoffmann, Ute Fiedler, Alberto Beltramello, and Joost P.A. Kuijer
Subjects: 0303 health sciences, Reproducibility, Epidemiology, Computer science, Health Policy, Multi site, Hyperintensity, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Segmentation, Neurology (clinical), Session (computer science), Geriatrics and Gerontology, Cartography, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2017

41. [P3–214]: ADFLAG ® , A DIAGNOSTIC BLOOD TEST FOR PRE‐DEMENTIA STAGES OF ALZHEIMER's DISEASE

Author: Pierre Payoux, Diego Albani, Pieter Jelle Visser, Samantha Galluzzi, Nathalie Compagnone, Clotilde Biscarrat, Beatrice Blanc, Lucilla Parnetti, Régis Bordet, Jorge Jovicich, Joëlle Micallef, Laura Lanteaume, Giovanni B. Frisoni, Moira Marizzoni, Jill C. Richardson, Bernard Michel, Peter Schoenknecht, David Bartrez-faz, Nicolas Pelletier, Olivier Blin, Mira Didic, Gianluigi Forloni, Ute Fiedler, Paolo Maria Rossini, Andrea Soricelli, Pauline Picamal, Magda Tsolaki, Flavio Nobili, and Julien Dupouey
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Diagnostic blood test, Internal medicine, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2017

42. Changes of metabolism and functional connectivity in late-onset deafness: Evidence from cerebral

Author: Antoine, Verger, Stéphane, Roman, Rose-May, Chaudat, Olivier, Felician, Mathieu, Ceccaldi, Mira, Didic, and Eric, Guedj
Subjects: Aged, 80 and over, Cerebral Cortex, Male, Aging, Brain Mapping, Auditory Pathways, Speech Intelligibility, Deafness, Middle Aged, Adaptation, Physiological, Magnetic Resonance Imaging, Hearing, Fluorodeoxyglucose F18, Predictive Value of Tests, Case-Control Studies, Positron-Emission Tomography, Speech Perception, Humans, Female, Age of Onset, Radiopharmaceuticals, Energy Metabolism, Aged
Abstract: Hearing loss is known to impact brain function. The aim of this study was to characterize cerebral metabolic Positron Emission Tomography (PET) changes in elderly patients fulfilling criteria for cochlear implant and investigate the impact of hearing loss on functional connectivity. Statistical Parametric Mapping-T-scores-maps comparisons of
Published: 2017

43. Contribution to Alzheimer's disease risk of rare variants in TREM_2, SORL_1, and ABCA_7 in 1779 cases and 1273 controls

Author: Céline Bellenguez, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Kilan Le Guennec, Gaël Nicolas, Ganesh Chauhan, David Wallon, Stéphane Rousseau, Anne Claire Richard, Anne Boland, Guillaume Bourque, Hans Markus Munter, Robert Olaso, Vincent Meyer, Adeline Rollin-Sillaire, Florence Pasquier, Luc Letenneur, Richard Redon, Jean-François Dartigues, Christophe Tzourio, Thierry Frebourg, Mark Lathrop, Jean-François Deleuze, Didier Hannequin, Emmanuelle Genin, Philippe Amouyel, Stéphanie Debette, Jean-Charles Lambert, Dominique Campion, Olivier Martinaud, Aline Zarea, Stéphanie Bombois, Marie-Anne Mackowiak, Vincent Deramecourt, Agnès Michon, Isabelle Le Ber, Bruno Dubois, Olivier Godefroy, Frédérique Etcharry-Bouyx, Valérie Chauviré, Ludivine Chamard, Eric Berger, Eloi Magnin, Jean-Francois Dartigues, Sophie Auriacombe, François Tison, Vincent de la Sayette, Dominique Castan, Elsa Dionet, Francois Sellal, Olivier Rouaud, Christel Thauvin, Olivier Moreaud, Mathilde Sauvée, Maïté Formaglio, Hélène Mollion, Isabelle Roullet-Solignac, Alain Vighetto, Bernard Croisile, Mira Didic, Olivier Félician, Lejla Koric, Mathieu Ceccaldi, Audrey Gabelle, Cecilia Marelli, Pierre Labauge, Thérèse Jonveaux, Martine Vercelletto, Claire Boutoleau-Bretonnière, Giovanni Castelnovo, Claire Paquet, Julien Dumurgier, Jacques Hugon, Foucauld De Boisgueheneuc, Serge Belliard, Serge Bakchine, Marie Sarazin, Marie-Odile Barrellon, Bernard Laurent, Frédéric Blanc, Jérémie Pariente, Snejana Jurici, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Excellence Laboratory LabEx DISTALZ, 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), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Metacohorts Consortium, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), McGill University and Genome Quebec Innovation Centre, Centre Hospitalier Régional Universitaire [Lille] (CHRU 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), Département de neurologie [Lille], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Institut National de la Santé et de la Recherche Médicale (Inserm)-Université de Bordeaux, Université de Bordeaux (UB), INSERM, Team Psycoépidémiologie du Vieillissement et des Maladies Chroniques - Population Health Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Lille, Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, Réseau International des Instituts Pasteur (RIIP), Department of Research, Centre hospitalier du Rouvray, Sotteville-lès-Rouen, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CNR MAJ collaborators, ANR-10-LABX-0013,GENMED,Medical Genomics(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 305299,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,AGEDBRAINSYSBIO(2013), 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), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Male, Adult, Aging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, SORL1, Apolipoprotein E4, Genome-wide association study, Biology, ABCA7, 03 medical and health sciences, Young Adult, Immunologic, Alzheimer Disease, Genetic variation, Receptors, medicine, 80 and over, TREM2, Humans, Genetic Predisposition to Disease, Receptors, Immunologic, Genetic Association Studies, LDL-Receptor Related Proteins, Aged, Aged, 80 and over, Genetics, Membrane Glycoproteins, Whole Genome Sequencing, General Neuroscience, Genetic Variation, Membrane Transport Proteins, Heritability, Middle Aged, Alzheimer's disease, medicine.disease, Minor allele frequency, 030104 developmental biology, biology.protein, ATP-Binding Cassette Transporters, Female, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology, Genome-Wide Association Study
Abstract: International audience; We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk~and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10$^{-6}$ was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a~clearer insight into the classes of rare variants involved. Despite different effect sizes and~varying~cumulative minor allele frequencies, the rare protein-truncating and missense-predicted~damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE $\varepsilon$4.
Published: 2017

44. Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects

Author: Pierre Payoux, Mira Didic, Régis Bordet, Manos Constantinidis, Stéphanie Bombois, Beatriz Bosch, Helene Gros-Dagnac, Magda Tsolaki, Roberto Tarducci, Moira Marizzoni, Marco Aiello, Agnese Picco, Ludovico Minati, Camillo Marra, Antonio Ferretti, Bernhard W. Müller, Carlo Cavaliere, Luca Roccatagliata, Massimo Caulo, Julien Sein, Ofer Pasternak, Andrea Soricelli, Angela Albi, Antonios Drevelegas, Jorge Jovicich, Núria Bargalló, Olivier Blin, Flavio Nobili, Jean-Philippe Ranjeva, Giada Zoccatelli, Renaud Lopes, Alberto Beltramello, David Bartrés-Faz, Ute Fiedler, Lucilla Parnetti, Jens Wiltfang, Giovanni B. Frisoni, Piero Floridi, Franco Alessandrini, Paolo Maria Rossini, University of Trento [Trento], IRCCS Fatebenefratelli - Brescia, Departament de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Casa di Cura SAN RAFFAELE Cassino e IRCCS SAN RAFFAELE PISANA, Clinical Neurology, Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Catholic University, Universität Duisburg-Essen [Essen], Magnetic Resonance Research Centre on Nervous System Diseases [Genova], Universita degli studi di Genova, Department of Health Sciences, University of Genoa, University of Genoa (UNIGE), Institut de Neurosciences de la Timone (INT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Troubles cognitifs dégénératifs et vasculaires (U1171), INSERM-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Nuclear Medicine, National Institute of Neurosurgery, University Hospital of Verona, Service of Neuroradiology [borgo trento], Ospedale Maggiore, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), SDN - Istituto di Ricerca Diagnostica e Nucleare, Department of Medicine [Perugia, Italy], Università degli Studi di Perugia (UNIPG), Perugia General Hospital, 3rd Department of Neurology, Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Metacohorts Consortium, Interbalkan Medical Center of Thessaloniki, 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, 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), Imagerie cérébrale et handicaps neurologiques (ICHN), Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università degli studi di Genova = University of Genoa (UniGe), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli Studi di Perugia = University of Perugia (UNIPG)
Subjects: Male, False discovery rate, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Medizin, Imaging, 030218 nuclear medicine & medical imaging, spatial statistics, ddc:616.89, 0302 clinical medicine, Nuclear Medicine and Imaging, 80 and over, test-retest reproducibility, Medicine, Longitudinal Studies, brain diffusion tensor imaging, alzheimers-disease, Aged, 80 and over, Radiological and Ultrasound Technology, Brain, multisite diffusion MRI, Middle Aged, tracking, White Matter, Healthy Volunteers, free-water imaging, healthy elderly, longitudinal, test–retest reproducibility, Anatomy, Radiology, Nuclear Medicine and Imaging, Neurology, Neurology (clinical), Settore MED/26 - NEUROLOGIA, Diffusion Tensor Imaging, medicine.anatomical_structure, Brain diffusion tensor imaging, Free-water imaging, Healthy elderly, Longitudinal, Multisite diffusion MRI, Test-retest reproducibility, Female, Aged, Anisotropy, Humans, Imaging, Three-Dimensional, Reproducibility of Results, Water, Radiology, MRI, Article, White matter, 03 medical and health sciences, cerebral white-matter, Fractional anisotropy, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Radiology, Nuclear Medicine and imaging, snc, Reproducibility, reliability, business.industry, Sample size determination, substantia-nigra, Three-Dimensional, Free water, Schizophrenia, parkinsons-disease, false discovery rate, business, Nuclear medicine, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: WOS:000390259700002; International audience; Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.
Published: 2017

45. Changes of metabolism and functional connectivity in late-onset deafness: Evidence from cerebral 18 F-FDG-PET

Author: Antoine Verger, Rose-May Chaudat, Stéphane Roman, Mira Didic, Eric Guedj, Mathieu Ceccaldi, Olivier Felician, Service de Médecine Nucléaire [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Nancyclotep- Experimental Imaging Platform = Plate-forme d'imagerie moléculaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), 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), ORL et Chirurgie cervico-faciale pédiatrique - [Hôpitaux Timone et Nord - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-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 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), Institut de Neurosciences de la Timone (INT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de Médecine Nucléaire [CHRU Nancy], and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Hearing loss, medicine.medical_treatment, Audiology, Deafness, Auditory cortex, Brain mapping, 050105 experimental psychology, 18F-FDG-PET, 03 medical and health sciences, 0302 clinical medicine, Elderly, Cochlear implant, medicine, Cingulum (brain), 0501 psychology and cognitive sciences, Connectivity, medicine.diagnostic_test, 05 social sciences, Neuropsychological test, Sensory Systems, medicine.anatomical_structure, Cerebral cortex, Connectome, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Hearing loss is known to impact brain function. The aim of this study was to characterize cerebral metabolic Positron Emission Tomography (PET) changes in elderly patients fulfilling criteria for cochlear implant and investigate the impact of hearing loss on functional connectivity. Statistical Parametric Mapping-T-scores-maps comparisons of 18F-FDG-PET of 27 elderly patients fulfilling criteria for cochlear implant for hearing loss (best-aided speech intelligibility lower or equal to 50%) and 27 matched healthy subjects (p < 0.005, corrected for volume extent) were performed. Metabolic connectivity was evaluated through interregional correlation analysis. Patients were found to have decreased metabolism within the right associative auditory cortex, while increased metabolism was found in prefrontal areas, pre- and post-central areas, the cingulum and the left inferior parietal gyrus. The right associative auditory cortex was integrated into a network of increased metabolic connectivity that included pre- and post-central areas, the cingulum, the right inferior parietal gyrus, as well as the striatum on both sides. Metabolic values of the right associative auditory cortex and left inferior parietal gyrus were positively correlated with performance on neuropsychological test scores. These findings provide further insight into the reorganization of the connectome through sensory loss and compensatory mechanisms in elderly patients with severe hearing loss.
Published: 2017

46. Association between CSF biomarkers, hippocampal volume and cognitive function in patients with amnestic mild cognitive impairment (MCI)

Author: Moira Marizzoni, Lucilla Parnetti, Pierre Payoux, Giovanni B. Frisoni, Claudio Babiloni, Tilman Hensch, José Luis Molinuevo, Pieter Jelle Visser, Jens Wiltfang, Nicola Salvadori, Camillo Marra, Annebet E. Leeuwis, Jill C. Richardson, Rosemary A. Abbott, Yen Ying Lim, Jorge Jovicich, Jean-Philippe Ranjeva, Bernhard W. Müller, Diego Albani, Pradeep J. Nathan, Elena Rolandi, Mira Didic, Magda Tsolaki, Samantha Galluzzi, Peter Schönknecht, Lucia Farotti, Nicola Girtler, Paolo Maria Rossini, Gianluigi Forloni, Olivier Blin, Flavio Nobili, David Bartrés-Faz, Andrea Soricelli, Régis Bordet, J. Pariente, IRCCS Fatebenefratelli - Brescia, San Raffaele Pisana IRCCS, Rome, Italy, Department of Physiology and Pharmacology Sapienza University of Rome, Departament de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Medicine [Perugia, Italy], Università degli Studi di Perugia (UNIPG), University Hospital Leipzig, University of Trento [Trento], Catholic University, Clinical Neurophysiology Service, Dept of Endocrinological and Metabolic Sciences, University of Ge, Centre Mémoire de Ressources et de Recherche [CHU de Toulouse, Hôpital Purpan], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Department of Nuclear Medicine, National Institute of Neurosurgery, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Casa di Cura SAN RAFFAELE Cassino e IRCCS SAN RAFFAELE PISANA, Clinical Neurology, Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), SDN - Istituto di Ricerca Diagnostica e Nucleare, 3rd Department of Neurology, Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Metacohorts Consortium, Department of Psychiatry and Neuropsychology, University of Maastricht, Universität Duisburg-Essen [Essen], 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), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), IRCCS San Giovanni, Laboratory of Epidemiology and Neuroimaging, Brescia, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Università degli Studi di Perugia = University of Perugia (UNIPG), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Centre Mémoire [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], 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), Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Troubles cognitifs dégénératifs et vasculaires (U1171), INSERM-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: 0301 basic medicine, Male, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Medizin, Neuropsychological Tests, Hippocampus, ddc:616.89, 0302 clinical medicine, Cerebrospinal fluid, Cognition, Mild cognitive impairment (MCI), Aged, 80 and over, medicine.diagnostic_test, General Neuroscience, Cambridge Neuropsychological Test Automated Battery, Middle Aged, Alzheimer's disease, Magnetic Resonance Imaging, Amyloid, CANTAB, Cognitive assessment, CSF, Hippocampal volume, Mild cognitive impairment, Prodromal, Tau, Neuroscience (all), Neurology (clinical), Developmental Biology, Geriatrics and Gerontology, Settore MED/26 - NEUROLOGIA, Geriatric Depression Scale, Female, Psychology, Elementary cognitive task, Neuroimaging, tau Proteins, 03 medical and health sciences, mental disorders, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, Aged, Amyloid beta-Peptides, Magnetic resonance imaging, medicine.disease, Peptide Fragments, 030104 developmental biology, Early Diagnosis, Neuroscience, 030217 neurology & neurosurgery, Biomarkers
Abstract: Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ42, tau and p-tau181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181 and increased tau/Aβ42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aβ and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD.
Published: 2017

47. Cognitive changes in mild cognitive impairment patients with impaired visual recognition memory

Author: Mathieu Ceccaldi, Julien Mancini, Emmanuel J. Barbeau, Francesca de Anna, Mira Didic, Olivier Felician, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), and Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, medicine.medical_specialty, Visual perception, Poison control, Neuropsychological Tests, Audiology, Standard score, behavioral disciplines and activities, 050105 experimental psychology, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Verbal fluency test, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Longitudinal Studies, Neuropsychological assessment, Cognitive decline, Aged, medicine.diagnostic_test, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Neuropsychology, Recognition, Psychology, Cognition, Middle Aged, Neuropsychology and Physiological Psychology, Disease Progression, Visual Perception, Female, Psychology, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objective: This study aims to evaluate whether assessing memory using the visual recognition memory task DMS48 in amnestic mild cognitive impairment (aMCI) can contribute to the early diagnosis of Alzheimer’s disease (AD). In an 18-month follow-up study, we assessed if longitudinal change in aMCI patients who failed on the DMS48 differs from that of patients who succeeded on this task at baseline. Method: Twenty-six controls and 33 aMCI patients underwent a complete neuropsychological assessment at baseline and at an 18-month follow-up. Patients were divided into two subgroups, according to their z score on the DMS48 (DMS48 subgroup succeeding; DMS48– subgroup failing on the task). In order to detect sensitive longitudinal change over time, we calculated and compared the standardized response mean (SRM) of performance on neuropsychological tasks in the three groups. Results: We found significant differences for the mean SRM of all neuropsychological tests when comparing DMS48 vs. controls vs. DMS48–, which was greatest for the comparison between the DMS48– and the DMS48 subgroup. Although cognitive profiles of the two patient subgroups at baseline did not differ in cognitive domains other than memory, we found a consistent decline on all neuropsychological tasks in the DMS48– subgroup compared with the DMS48 subgroup, except for performance on a verbal fluency test. Conclusions: As the cognitive profile of the DMS48– subgroup at follow-up resembles the typical pattern of AD described in the literature, this study confirms that visual recognition memory tasks may be useful to anticipate covert cognitive decline in aMCI patients.
Published: 2014

48. Functional connectivity changes differ in early and late-onset alzheimer's disease

Author: Jean-Philippe Ranjeva, Mathieu Ceccaldi, Maxime Guye, Claude Gueriot, Olivier Felician, Mira Didic, Valérie Chanoine, Natalina Gour, Lejla Koric, and Sylviane Confort-Gouny
Subjects: Radiological and Ultrasound Technology, medicine.diagnostic_test, Magnetic resonance imaging, Late onset, medicine.disease, Executive functions, Temporal lobe, Basal (phylogenetics), Atrophy, Neurology, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Neuropsychological assessment, Anatomy, Psychology, Neuroscience, Default mode network
Abstract: At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting-state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso-lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double-dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes.
Published: 2013

49. Apport des biomarqueurs cognitifs dans le diagnostic de la maladie d’Alzheimer

Author: Olivier Felician, Emmanuel J. Barbeau, Mira Didic, and Mathieu Ceccaldi
Subjects: Neurology (clinical)
Abstract: Resume Le diagnostic de certitude de la maladie d’Alzheimer (MA) reste fonde sur la confirmation neuropathologique, mais la caracterisation clinique precise des deficits cognitifs et comportementaux reste un element determinant dans l’approche diagnostique et permet tres souvent de predire la proteinopathie a l’origine du processus pathologique sous-jacent. De nombreux travaux s’interessent au diagnostic precoce de cette maladie, aux stades ou les lesions neuropathologiques sont encore circonscrites. Les premiers stades des affections degeneratives du cortex cerebral se caracterisant par l’atteinte selective de circuits neuronaux, une meilleure connaissance des reseaux neuraux affectes dans les premiers stades des processus degeneratifs pathologiques parait capitale pour ameliorer le diagnostic clinique de maniere generale, et notamment le diagnostic precoce. Prenant en compte la progression des degenerescences neurofibrillaires dans la region temporale interne dans la MA debutante, nous avons recemment formule l’hypothese selon laquelle, au stade transentorhinal – le stade le plus precoce de la degenerescence neurale – les lesions seraient a l’origine d’une dysfonction du systeme mesiotemporal anterieur et responsables de troubles de la memoire decontextualisee (memoire des faits et des connaissances). Ce ne serait que plus tardivement, au stade limbique, que l’atteinte du systeme mesiotemporal posterieur entrainerait une atteinte de la memoire contextualisee (memoire episodique). Nous presentons ici une approche translationnelle dans laquelle l’appreciation des processus cognitifs par les methodes de la neuropsychologie, basee sur les donnees neuropathologiques de la MA, est concue comme indicatrice d’un dysfonctionnement lie a un processus pathologique en tant que « biomarqueur cognitif » et etudiee en conjonction avec l’apport des methodes de neuroimagerie.
Published: 2013

50. Contents Vol. 35, 2013

Author: Constanze Lahmeyer, Matthias W. Riepe, N. Schupf, Raita Fukazawa, John Weinman, K. Martikainen, Robert T. Woods, Roseanna Brady, J.H. Lee, Judith Roberts, F. Matharan, Friedemann Müller, Anthony Martyr, V. Condret-Santi, S. Laatu, Shunichi Koyama, Haruo Hanyu, Sharon M. Nelis, R. Cheng, Emmanuel J. Barbeau, Hirofumi Sakurai, Maria Lage Barca, Maria Eriksdotter, Julien Mancini, Soichiro Shimizu, Barbara Romero, Joe Hirman, M. Le Goff, Christina Jonas, Tomohiko Sato, Druck Reinhardt Druck Basel, N. Park, L.N. Clark, Christopher J. Whitaker, Michael Gold, Kristina Johnell, Knut Engedal, Andrew D. Blackwell, Olivier Felician, J.-F. Dartigues, Mira Didic, Claudia Schiffczyk, Robin G. Morris, Ilona Roth, Dorota Religa, E.J. Barbeau, Eve Tramoni, Bruce H. Morimoto, Mathieu Ceccaldi, M. Karrasch, S.C. Janicki, R. Marttila, Hidekazu Kanetaka, Linda Clare, Julian Keith, Don Schmechel, Caroline Latger-Florence, Ivana Marková, H. Amieva, Anne-Brita Knapskog, and Toshihiko Iwamoto
Subjects: Psychiatry and Mental health, Cognitive Neuroscience, Geriatrics and Gerontology
Published: 2013

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