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Your search keyword '"INSERM U897, University of Bordeaux, France"' showing total 11 results
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11 results on '"INSERM U897, University of Bordeaux, France"'

1. Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRAS G12D -driven Pancreatic Tumorigenesis

Author

Jennifer P. Morton, Sylvie Martel, Cassandre Caligaris, Isabelle Goddard, Julie Guillermet, Victoire Cardot, Emilie Servoz, Laurent Bartholin, David F. Vincent, Amélie Colombe, Anne Couvelard, Vinciane Rebours, Isabelle Treilleux, Karam Yacoub, Elodie Roger, Johann Gout, Pierre Dubus, Julie Valantin, Bastien Kaniewski, Ulrich Valcourt, Nicolas Gadot, Roxane M. Pommier, Sophie Goddard-Léon, Célia Cintas, Owen J. Sansom, Nicolas Chuvin, Lindsay B. Alcaraz, Stéphanie Sentis, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Reproduction et développement des plantes (RDP), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université d'Artois (UA), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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)-Centre National de la Recherche Scientifique (CNRS), Beatson Institute for Cancer Research [Glasgow, Royaume-Uni], Département d'Anatomo-Pathologie [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Beatson Institute for Cancer Research, Beatson institute for cancer research, Histologie et Pathologie Moléculaire des Tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, INSERM U897, University of Bordeaux, France, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Beatson Institute for Cancer Research, University of Glasgow, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Hepatology, Gastroenterology, Pancreatic Intraepithelial Neoplasia, Pancreas Cancer TGFβ Acinar-to-Ductal Metaplasia KRASG12D, [SDV.CAN]Life Sciences [q-bio]/Cancer, SMAD, Transforming growth factor beta, Biology, medicine.disease, medicine.disease_cause, 3. Good health, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Pancreatic tumor, Pancreatic cancer, medicine, biology.protein, Cancer research, lcsh:Diseases of the digestive system. Gastroenterology, KRAS, lcsh:RC799-869, Pancreas, Carcinogenesis
Abstract

Background & Aims: Transforming growth factor beta (TGFβ) acts either as a tumor suppressor or as an oncogene, depending on the cellular context and time of activation. TGFβ activates the canonical SMAD pathway through its interaction with the serine/threonine kinase type I and II heterotetrameric receptors. Previous studies investigating TGFβ-mediated signaling in the pancreas relied either on loss-of-function approaches or on ligand overexpression, and its effects on acinar cells have so far remained elusive. Methods: We developed a transgenic mouse model allowing tamoxifen-inducible and Cre-mediated conditional activation of a constitutively active type I TGFβ receptor (TβRICA) in the pancreatic acinar compartment. Results: We observed that TβRICA expression induced acinar-to-ductal metaplasia (ADM) reprogramming, eventually facilitating the onset of KRASG12D-induced pre-cancerous pancreatic intraepithelial neoplasia. This phenotype was characterized by the cellular activation of apoptosis and dedifferentiation, two hallmarks of ADM, whereas at the molecular level, we evidenced a modulation in the expression of transcription factors such as Hnf1β, Sox9, and Hes1. Conclusions: We demonstrate that TGFβ pathway activation plays a crucial role in pancreatic tumor initiation through its capacity to induce ADM, providing a favorable environment for KRASG12D-dependent carcinogenesis. Such findings are highly relevant for the development of early detection markers and of potentially novel treatments for pancreatic cancer patients. Keywords: Pancreas, Cancer, TGFβ, Acinar-to-Ductal Metaplasia, KRASG12D

Published
2017

2. White Matter Lesions are Associated with Specific Depressive Symptom Trajectories among Incident Depression and Dementia Populations: Three-City Dijon MRI Study

Author

Christophe Tzourio, Bernard Mazoyer, Phillip J. Tully, Stéphanie Debette, INSERM U897, University of Bordeaux, France, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Male, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Dementia, Humans, Longitudinal Studies, Psychiatry, Stroke, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, 030214 geriatrics, Depression, [SCCO.NEUR]Cognitive science/Neuroscience, Incidence, Confounding, Center for Epidemiologic Studies Depression Scale, medicine.disease, Magnetic Resonance Imaging, White Matter, Confidence interval, Hyperintensity, 3. Good health, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, France, Geriatrics and Gerontology, Psychology, 030217 neurology & neurosurgery, Geriatric psychiatry
Abstract

Objective Evidence is mixed as to whether periventricular or deep white matter hyperintensities (WMHs) increase the risk for depressive symptoms, partly because of heterogeneity in depression measurement, short follow-up, and confounding by prodromal dementia. The study objective was to evaluate WMH volume in relation to discrete depressive symptoms over 10 years, stratifying by incident depression and dementia. Methods In this prospective longitudinal cohort study of a representative population sample from Dijon, France, 1,440 participants aged 65–80 years (median age: 72 years; 59.5% women) without depression, dementia, or stroke at baseline were studied. Baseline T2-weighted images were obtained in a 1.5-T scanner to quantify WMHs (log cm 3 ). Clinic visits were performed up to five times in a 10-year period to assess incident neurologic diseases and comorbidities. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale and converted to factor z scores, representing somatic symptoms, depressed affect, low positive affect, and interpersonal problems. Results Periventricular WMH volume was uniquely associated with low positive affect among incident depression cases (β = 0.15; 95% confidence interval [CI]: 0.02–0.29; p = 0.026). Deep WMH volume was uniquely associated with depressed affect among incident dementia cases (β = 0.36; 95% CI: 0.05–0.68; p = 0.025). WMH volume (periventricular, deep, and total) was associated with interpersonal problems among persons who developed dementia with depression. Conclusion The findings highlight that regional WMH volumes and specific depressive symptoms have clinical and prognostic relevance to help differentiate between persons at risk for depression and dementia.

Published
2017

3. Differential Effect of White-Matter Lesions and Covert Brain Infarcts on the Risk of Ischemic Stroke and Intracerebral Hemorrhage: Table

Author

Christophe Tzourio, Yi-Cheng Zhu, Stephanie Debette, Sara Kaffashian, B Mazoyer, INSERM U897, University of Bordeaux, France, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Materials Science Division [LBNL Berkeley], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Male, Risk, medicine.medical_specialty, brain, Population, behavioral disciplines and activities, Brain Ischemia, infarctioncerebral hemorrhage, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, education, Stroke, Aged, Cerebral Hemorrhage, Aged, 80 and over, Advanced and Specialized Nursing, Intracerebral hemorrhage, education.field_of_study, medicine.diagnostic_test, business.industry, Incidence, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, Magnetic resonance imaging, Cerebral Infarction, medicine.disease, Magnetic Resonance Imaging, White Matter, stroke, Hyperintensity, nervous system diseases, cerebral small-vessel diseases, Covert, Anesthesia, Ischemic stroke, Cardiology, Female, France, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background and Purpose— We examined the association of white-matter hyperintensity (WMH) volume and covert brain infarcts, which are the 2 major magnetic resonance imaging markers of covert cerebrovascular disease in older adults, with long-term risk of ischemic stroke and intracerebral hemorrhage (ICH) in the general population. Methods— Participants were 1731 individuals aged ≥65 years from the Three-City Dijon study. We studied the association of WMH volume and brain infarct, with incident ischemic stroke overall, and by subtype, and with incident ICH. Results— High total, periventricular, and deep WMHs were associated with incident ICH. Extensive periventricular WMH volume was associated with increased risk of ischemic stroke (hazard ratio, 1.94; 95% confidence interval, 1.12–3.35), particularly cardioembolic stroke. Covert brain infarcts were associated with incident ICH but not with incident ischemic stroke or its subtypes. Conclusions— Although of ischemic nature, both WMH volume and covert brain infarcts portend a major risk of ICH. If confirmed in independent studies, these findings could have important implications for the clinical management of covert vascular brain lesions.

Published
2016

4. Association of plasma β-amyloid with MRI markers of structural brain aging the 3-City Dijon study

Author

Carole Dufouil, Luc Buée, Christophe Tzourio, Aicha Soumare, Susanna Schraen-Maschke, Sara Kaffashian, Bernard Mazoyer, Stéphanie Debette, INSERM U897, University of Bordeaux, France, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Inserm UMR837 Team 5, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
Male, medicine.medical_specialty, Pathology, Aging, Amyloid, Brain atrophy, Hippocampus, computer.software_genre, 03 medical and health sciences, Plasma, 0302 clinical medicine, Atrophy, Cerebrospinal fluid, Voxel, Internal medicine, Medicine, Humans, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Amyloid beta-Peptides, Brain volume, medicine.diagnostic_test, business.industry, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Magnetic resonance imaging, Organ Size, medicine.disease, Magnetic Resonance Imaging, Hippocampal volume, Peptide Fragments, Endocrinology, Brain size, Female, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, Alzheimer disease, business, computer, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology, Follow-Up Studies
Abstract

International audience; Cerebral β-amyloid (Aβ) deposition and atrophy are central features of Alzheimer disease. Studies of Alzheimer disease biomarkers have largely focused on Aβ in cerebrospinal fluid (CSF), and there is uncertainty as to what plasma Aβ may be a marker. We examined the association of Aβ levels in the plasma with magnetic resonance imaging (MRI)-markers of brain aging, including longitudinal changes in global and regional brain volumes, in dementia-free persons. We studied 1530 participants of the Three-City-Dijon cohort, aged 65-80 years. Plasma Aβ measurement and magnetic resonance imaging were performed at baseline and after a 4-year follow up. Total brain, gray matter, and hippocampal volume were estimated using voxel-based morphometry, and annualized change in brain volumes was calculated. Increased plasma Aβ1-40 was associated with lower baseline hippocampal volume. Although baseline plasma Aβ levels were not associated with longitudinal change in brain volumes, consistently high plasma Aβ1-40 levels were associated with faster total brain atrophy and consistently low plasma Aβ1-42/Aβ1-40 ratio, with increased total brain atrophy and gray matter atrophy. In dementia-free older adults, high plasma Aβ1-40 and low plasma Aβ1-42/Aβ1-40 ratio were associated with smaller hippocampal volume and accelerated global and regional brain atrophy respectively.

Published
2015

5. Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease

Author

Amir Ait Ameur, Enrica Cavedo, Simone Lista, Olivier Rouaud, Florence Pasquier, Jacques Touchon, Pierre Jean Ousset, Isabelle Tonelli, Mathieu Ceccaldi, Marie Sarazin, Alain Vighetto, Marie Chupin, Nadine Girard, Françoise Duveau, Didier Dormont, Guy Louis Tisserand, Frédéric Ricolfi, Christine Delmaire, Alain Bonafe, Line Garnero, Bernard Croisile, Bruno Dubois, Olivier Colliot, Carole Dufouil, Stéphane Lehéricy, Harald Hampel, 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Department of Psychiatry, Psychosomatic Medicine and Psychotherapy [Goethe Universität], Goethe-Universität Frankfurt am Main, Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Casselardit - Junod, Clinique Pasteur, Clinique Pasteur [Toulouse], Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de neurologie [Lille], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Roger Salengro [Lille], Hôpital de la Timone [CHU - APHM] (TIMONE), INSERM U897, University of Bordeaux, France, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Eisai, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Hippocampus Study Group, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and 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 Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Male, Epidemiology, Disease, Gastroenterology, Hippocampus, law.invention, 0302 clinical medicine, Randomized controlled trial, Piperidines, law, Hippocampus (mythology), Donepezil, 0303 health sciences, education.field_of_study, Health Policy, Organ Size, Magnetic Resonance Imaging, Hippocampal atrophy, 3. Good health, Psychiatry and Mental health, Neuroprotective Agents, Treatment Outcome, Indans, Disease Progression, Biomarker (medicine), Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, medicine.drug, medicine.medical_specialty, Population, Prodromal Symptoms, Placebo, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Double-Blind Method, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Psychiatry, education, 030304 developmental biology, Aged, Neurology (clinical), Geriatrics and Gerontology, Atrophy, 030217 neurology & neurosurgery
Abstract

International audience; INTRODUCTION:The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD).METHODS:A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method.RESULTS:Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P < .001. There was no significant difference in neuropsychological performance between treatment groups.DISCUSSION:A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.

Published
2015

6. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Author

Susan H. Blanton, Ashley Beecham, Pamela J. Schreiner, Ralph L. Sacco, Stéphanie Debette, Ben A. Oostra, Marian Beekman, M. Arfan Ikram, Edith Hofer, Anna Maria Töglhofer, Alexander Teumer, Ganesh Chauhan, Clinton B. Wright, Meike W. Vernooij, Wiro J. Niessen, Aad van der Lugt, Cornelia M. van Duijn, Christophe Tzourio, Matthias Nauck, Bernard Mazoyer, Bettina von Sarnowski, Alexa S. Beiser, Susan R. Heckbert, André G. Uitterlinden, Alex P. Zijdenbos, David S. Knopman, Paul Freudenberger, Myriam Fornage, Maaike Schuur, Stephen Turner, Matthew Traylor, Qiong Yang, Fabrice Crivello, P. Eline Slagboom, Ian J. Deary, Sharon L.R. Kardia, Cora E. Lewis, Stella Trompet, Mike A. Nalls, Jennifer A. Smith, Katrin Hegenscheid, Hans J. Grabe, Lenore J. Launer, Reinhold Schmidt, Albert V. Smith, M. Kamran Ikram, Kumar B. Rajan, Mariza de Andrade, Sudha Seshadri, Lorna M. Lopez, Philip L. De Jager, Albert Hofman, Joshua C. Bis, Gerardo Heiss, Neelum T. Aggarwal, Elizabeth J. Atkinson, Carla A. Ibrahim-Verbaas, David C. Liewald, Anton J. M. de Craen, Jing Wang, David J. Stott, Sandra Barral, Adam M. Brickman, Mohamad Habes, Eric Boerwinkle, Katharina Wittfeld, Jerome I. Rotter, Saima Hilal, R. Nick Bryan, Charles C. DeCarli, Mark A. van Buchem, Mitchell S.V. Elkind, Rebecca F. Gottesman, Christiane Wolf, Vincent Chouraki, Jeroen van der Grond, Jiemin Liao, Joris Deelen, Stephen Sidney, Kenneth Rice, Vilmundur Guðnason, Hieab H.H. Adams, Benjamin F.J. Verhaaren, Tien Yin Wong, Oliver Martinez, Denis A. Evans, Helena Schmidt, W. T. Longstreth, J. Wouter Jukema, Richard Mayeux, Joanna M. Wardlaw, Thomas H. Mosley, Michelle Luciano, Sigurdur Sigurdsson, Carole Dufouil, Christopher Chen, Philippe Amouyel, Wei Zhao, John C. van Swieten, Bruce M. Psaty, Hae-Won Uh, B. Gwen Windham, Erasmus University Medical Center [Rotterdam] (Erasmus MC), INSERM U897, University of Bordeaux, France, University of Washington [Seattle], University of Michigan [Ann Arbor], University of Michigan System, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Rush University Medical Center [Chicago], University of Edinburgh, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, Depts of Radiology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Greifswald University Hospital, Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Biomedical Statistics and Informatics, Mayo Clinic, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Genetics, The University of Texas Health Science Center at Houston (UTHealth), Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University [New York], Perelman School of Medicine, University of Pennsylvania, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Department of neurology, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dept of Psychology, Molecular Epidemiology, Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Columbia Mailman School of Public Health, Laboratoire pharmaceutique Lilly France [Neuilly-sur-Seine], Institute of Molecular Biology & Biochemistry, Johns Hopkins University School of Medicine [Baltimore], Faculty of Medicine, University of Iceland [Reykjavik], The Icelandic Heart Association, Kopavogur, Iceland, Institutes for Community Medicine, Department of Epidemiology, University of Washington, Group Health Research Institute, Group Health Cooperative, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), National University of Singapore (NUS), Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Langage, lettres et arts du spectacle, information et communication - Dpt Sciences de l'information et de la communication (UGA UFR LLASIC SIC), Mayo Clinic [Rochester], Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, East China University of Science and Technology, Medstar Research Institute, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics, GlaxoSmithKline, National Institutes of Health [Bethesda] (NIH), Institute of Clinical Chemistry and Laboratory Medicine, Universität Greifswald - University of Greifswald, Delft University of Technology (TU Delft), Cardiovascular Health Research Unit, University of Washington, Department of Medicine, University of Washington, Department of Health Services, University of Washington, Department of Biostatistics, University of Washington, Cedars-Sinai Medical Center, Dept of Neurology, Univ Medicine of Greifswald, Germany, Department of Physics [Stockholm], Stockholm University, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Kaiser Permanente, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Uppsala University, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, King‘s College London, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, Research Centre for Stroke & Dementia, St George 's Univ of London, Interuniversity Cardiology Institute Netherlands, SAC, Bush Estate, School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Singapore Eye Research Institute, Singapore National Eye Centre, University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Dundee Technopole, CXR Biosciences Ltd, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan System-University of Michigan System, University of Miami [Coral Gables], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biospective [Montréal], Dept of Epidemiology & Public Health Sciences, 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), University of Mississippi Medical Center (UMMC), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Austrian Institute of Technology [Vienna] (AIT), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Human Genetics Center, University of Pennsylvania [Philadelphia], Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Memory Aging & Cognition Centre, National Univ of Singapore, Singapore, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Dept of Ophthalmology, National Univ of Singapore & National Univ Health System, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of California-University of California, Radboud university [Nijmegen], Epidemiology, Radiology & Nuclear Medicine, General Practice, Neurology, Medical Informatics, Clinical Genetics, Internal Medicine, Human genetics, NCA - neurodegeneration, Hal, GIN, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and HESAM Université (HESAM)-HESAM Université (HESAM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, Male, single nucleotide, Pathology, Genome-wide association study, leukoencephalopathies, polymorphisms, single nucleotide, Chromosomes, Human, Genetics (clinical), Aged, 80 and over, education.field_of_study, Continental Population Groups, cerebrovascular disorders, Middle Aged, White Matter, 3. Good health, Stroke, genetics [Stroke], Female, cerebral small vessel diseases, Alzheimer's disease, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, hypertension, Population, genetics [Chromosomes, Human], Article, Meta-Analysis as Topic, Internal medicine, Genetics, medicine, Dementia, Humans, ddc:610, 1000 Genomes Project, education, Genetic association, Aged, Intracerebral hemorrhage, genome-wide association study, Models, Genetic, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Racial Groups, medicine.disease, ethnology [Stroke], Hyperintensity, Genetic Loci, pathology [Stroke], business, polymorphisms, Genome-Wide Association Study
Abstract

Background— The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results— We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 ( P =2.7×10 −19 ) and identified novel loci on chr10q24 ( P =1.6×10 −9 ) and chr2p21 ( P =4.4×10 −8 ). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 ( P =2.0×10 −8 ) and chr2p16 ( P =1.5×10 −8 ). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions— We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.

Published
2015

7. Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

Author

Debra A. Fleischman, Helena Schmidt, Wiro J. Niessen, David S. Knopman, Sven J. van der Lee, Clifford R. Jack, Joshua C. Bis, Russell Thomson, James T. Becker, Konstantinos Arfanakis, Charles DeCarli, Christophe Tzourio, Myriam Fornage, Qiong Yang, Meike W. Vernooij, Ganesh Chauhan, Hieab H.H. Adams, Bernard Mazoyer, Oscar L. Lopez, Cornelia M. van Duijn, Philippe Amouyel, William T. Longstreth, Lenore J. Launer, Rebecca F. Gottesman, Albert V. Smith, Thanh G. Phan, Richard Beare, Anna Maria Töglhofer, Stéphanie Debette, Lei Yu, Sudha Seshadri, Albert Hofman, Velandai Srikanth, Galit Weinstein, Thomas H. Mosley, Reinhold Schmidt, Jing Wang, David A. Bennett, M. Arfan Ikram, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), University of Washington [Seattle], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Hangzhou Dianzi University (HDU), Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Johns Hopkins University School of Medicine [Baltimore], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), University of Miami [Coral Gables], Delft University of Technology (TU Delft), Estación Experimental de Pastos y Forrajes ‘Indio Hatuey’, Karlsruhe Institute of Technology (KIT), Institut de Mathématiques [Hanoi], Académie des Sciences et Techniques, Murdoch Children's Research Institute (MCRI), Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], Department of Radiology, Mayo Clinic, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, Mayo Clinic [Rochester], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Austrian Institute of Technology [Vienna] (AIT), University of Mississippi Medical Center (UMMC), Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], INSERM U897, University of Bordeaux, France, University of Tasmania (UTAS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of California-University of California, Radboud university [Nijmegen], Epidemiology, and Radiology & Nuclear Medicine

Subjects
Oncology, Apolipoprotein E, Male, Aging, Sialic Acid Binding Ig-like Lectin 3, Genome-wide association study, Neurodegenerative, Alzheimer's Disease, Bioinformatics, Hippocampus, [SCCO]Cognitive science, 0302 clinical medicine, GWAS, 2.1 Biological and endogenous factors, Aetiology, screening and diagnosis, 0303 health sciences, education.field_of_study, General Neuroscience, Brain, Single Nucleotide, Organ Size, Magnetic Resonance Imaging, Genetic risk score, 3. Good health, Detection, Neurological, Brain size, Female, MRI-Markers, Alzheimer's disease, Psychology, Risk, medicine.medical_specialty, Clinical Sciences, Population, Locus (genetics), Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Apolipoproteins E, Clinical Research, Alzheimer Disease, Internal medicine, Acquired Cognitive Impairment, Genetics, medicine, Humans, Polymorphism, Allele, education, Alleles, 030304 developmental biology, Genetic association, Neurology & Neurosurgery, Prevention, [SCCO.NEUR]Cognitive science/Neuroscience, Human Genome, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Hippocampal volume, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Alzheimer, Dementia, Neurology (clinical), Geriatrics and Gerontology, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta +/- SE = -0.047 +/- 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. (C) 2015 Elsevier Inc. All rights reserved.

Published
2015

8. Predictors of delayed stroke in patients with cervical artery dissection

Author

Turgut Tatlisumak, C. Lamy, Emmanuel Touzé, Valeria Caso, Stefan T. Engelter, Tobias Brandt, Vincent Thijs, Maria Sessa, Anna Bersano, Yves Samson, Alessandro Pezzini, Elisabeth De Bustos Medeiros, Christoph Lichy, Philippe Lyrer, Sherine Abboud, Antti J. Metso, Stéphanie Debette, Armin J. Grau, Tiina M. Metso, Simone Beretta, Manja Kloss, Didier Leys, Caspar Grond-Ginsbach, INSERM U897, University of Bordeaux, France, Department of Medical Neurobiology [Jérusalem], The Hebrew University of Jerusalem (HUJ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratory of Experimental Stroke Research, Department of Surgery and Translational Medicine, University of Milano Bicocca, Neuromi, Milan Center for Neuroscience, Centre d'Etudes Supérieures de Civilisation médiévale (CESCM), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB)-Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), CHU Amiens-Picardie, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB)-Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Cervical Artery, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral artery dissection, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Ischemia, Horner syndrome, Dissection (medical), Carotid artery dissection, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, cardiovascular diseases, Stroke, Vertebral Artery Dissection, 2. Zero hunger, business.industry, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Middle Aged, medicine.disease, 3. Good health, Surgery, Neurology, Migraine, Ischemic Attack, Transient, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Cardiology, Female, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

Background Stroke in patients with acute cervical artery dissection may be anticipated by initial transient ischemic or nonischemic symptoms. Aim Identifying risk factors for delayed stroke upon cervical artery dissection. Methods Cervical artery dissection patients from the multicenter Cervical Artery Dissection and Ischemic Stroke Patients study were classified as patients without stroke ( n = 339), with stroke preceded by nonstroke symptoms (delayed stroke, n = 244), and with stroke at onset ( n = 382). Demographics, clinical, and vascular findings were compared between the three groups. Results Patients with delayed stroke were more likely to present with occlusive cervical artery dissection ( P < 0·001), multiple cervical artery dissection ( P = 0·031), and vertebral artery dissection ( P < 0·001) than patients without stroke. No differences were observed in age, smoking, arterial hypertension, hypercholesterolemia, migraine, body mass index, infections during the last week, and trauma during the last month, but patients with delayed stroke had less often transient ischemic attack ( P < 0·001) and local signs (Horner syndrome and cranial nerve palsy; P < 0·001). Conclusions Occlusive cervical artery dissection, multiple cervical artery dissection, and vertebral artery dissection were associated with an increased risk for delayed stroke. No other risk factors for delayed stroke were identified. Immediate cervical imaging of cervical artery dissection patients without ischemic stroke is needed to identify patients at increased risk for delayed ischemia.

Published
2015

9. Generating and executing complex natural language queries across linked data

Author

Hamon, Thierry, Mougin, Fleur, Grabar, Natalia, Publications, Limsi, Laboratoire d'Informatique pour la Mécanique et les Sciences de l'Ingénieur (LIMSI), Université Paris Saclay (COmUE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université - UFR d'Ingénierie (UFR 919), Sorbonne Université (SU)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11), Université Paris 13 (UP13), INSERM U897, University of Bordeaux, France, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Sorbonne Université - UFR d'Ingénierie (UFR 919), and Sorbonne Université (SU)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Saclay (COmUE)

Subjects
Knowledge Databases, [INFO.INFO-CL] Computer Science [cs]/Computation and Language [cs.CL], Linked Data, frames, [INFO]Computer Science [cs], [INFO] Computer Science [cs], biomedical domain, SPARQL, [INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL], Natural Language Processing, semantic resources
Abstract

International audience; With the recent and intensive research in the biomedicalarea, the knowledge accumulated is disseminated throughvarious knowledge bases. The combined exploitation of thisknowledge is important, which requires to create links be-tween these bases and to use them jointly. Linked Data, SPARQL language and interfaces in Natural Language question-answering provide interesting solutions for querying such knowledge bases. We propose a method for translating natural language questions in SPARQL queries. We use Natural Language Processing tools, semantic resources and the RDF triples description. The method is designed on 50 questions over 3 biomedical knowledge bases, and evaluated on 27 questions. It achieves 0.78 F-measure on the test set. The method for translating natural language questions into SPARQL queries is implemented as Perl module available at http://search.cpan.org/~thhamon/RDF-NLP-SPARQLQuery

Published
2015

10. Familial occurrence and heritable connective tissue disorders in cervical artery dissection

Author

Ayse Altintas, Didier Leys, Paolo Costa, Ralf W. Baumgartner, Christian Stapf, Stefano Paolucci, Valeria Caso, Anna Bersano, Yves Samson, Yannick Béjot, Barbara Goeggel Simonetti, Sabrina Schilling, Emmanuel Touzé, Caspar Grond-Ginsbach, Philippe Lyrer, Urs Fischer, C. Lamy, Tobias Brandt, Antti J. Metso, Stefan T. Engelter, Juan Jose Martin, Jean Dallongeville, Hugues Chabriat, Michael Frank, Manja Kloss, Elisabeth Tournier-Lasserve, Vincent Thijs, Maria Sessa, Ingrid Hausser, Christoph Lichy, Marcel Arnold, Dominique P. Germain, Stéphanie Debette, Alessandro Pezzini, Simon Jung, Turgut Tatlisumak, Marie-Germaine Bousser, Armin J. Grau, Tiina M. Metso, Dominique Hervé, Hakan Sarikaya, INSERM U897, University of Bordeaux, France, Department for Internal Medicine, Staedtische Kliniken Moenchengladbach, DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Heidelberg [Heidelberg], Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de physique des interfaces et des couches minces [Palaiseau] (LPICM), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Institute for Infectiology (IMED), Friedrich-Loeffler-Institut (FLI), Centre d'Etudes Supérieures de Civilisation médiévale (CESCM), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Deparment of Neurology (LARIBOISIERE - Neurologie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), AP-HP Hôpital Raymond Poincaré [Garches], GEOMAR - Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Université Paris Diderot - Paris 7 (UPD7), U 744, Laboratoire d’Epidémiologie et de Santé Publique, Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (Inserm)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Raymond Poincaré [AP-HP], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Université Lille Nord de France (COMUE)-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), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), DAM Île-de-France ( DAM/DIF ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de physique des interfaces et des couches minces [Palaiseau] ( LPICM ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Institute for Infectiology ( IMED ), Friedrich-Loeffler-Institut ( FLI ), Centre d'Etudes Supérieures de Civilisation médiévale ( CESCM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Écophysiologie des Plantes sous Stress environnementaux ( LEPSE ), Institut National de la Recherche Agronomique ( INRA ) -Centre international d'études supérieures en sciences agronomiques ( Montpellier SupAgro ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ), Deparment of Neurology ( LARIBOISIERE - Neurologie ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), GEOMAR - Helmholtz Centre for Ocean Research [Kiel] ( GEOMAR ), Université Paris Diderot - Paris 7 ( UPD7 ), Université Lille Nord de France-Institut National de la Santé et de la Recherche Médicale ( Inserm ) -Institut Pasteur de Lille, Centre européen de recherche et d'enseignement de géosciences de l'environnement ( CEREGE ), and Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Collège de France ( CdF ) -Institut National de la Recherche Agronomique ( INRA ) -Institut national des sciences de l'Univers ( INSU - CNRS )

Subjects
Marfan syndrome, Male, Pathology, Internationality, Cervical Artery, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral artery dissection, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, 030204 cardiovascular system & hematology, [ INFO.INFO-CV ] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Cohort Studies, 0302 clinical medicine, [ INFO.INFO-TI ] Computer Science [cs]/Image Processing, MESH : Female, 030212 general & internal medicine, Family history, Connective Tissue Diseases, MESH: Cohort Studies, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral Artery Dissection, MESH: Middle Aged, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, MESH : Adult, Middle Aged, 3. Good health, Dissection, medicine.anatomical_structure, Osteogenesis imperfecta, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], MESH : Connective Tissue Diseases, Female, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Cohort study, Adult, medicine.medical_specialty, MESH : Male, MESH : Cohort Studies, Connective tissue, MESH: Vertebral Artery Dissection, Dissection (medical), Article, 03 medical and health sciences, MESH : Internationality, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, MESH : Middle Aged, MESH: Connective Tissue Diseases, MESH: Humans, MESH : Vertebral Artery Dissection, business.industry, MESH : Humans, Correction, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, medicine.disease, MESH: Male, Surgery, Ehlers–Danlos syndrome, MESH: Internationality, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract

Erratum in: Familial occurrence and heritable connective tissue disorders in cervical artery dissection. [Neurology. 2016]; International audience; In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

Published
2014

11. Plasma β-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon study

Author

Luc Buée, Carole Dufouil, Aïcha Soumaré, B Mazoyer, Pauline Maillard, Fabrice Crivello, Sara Kaffashian, Susanna Schraen-Maschke, Stephanie Debette, Christophe Tzourio, Yi-Cheng Zhu, INSERM U897, University of Bordeaux, France, Department of Neurology, Peking Union Medical College Hospital, Beijing, China, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of California [Davis] (UC Davis), University of California (UC), Inserm UMR837 Team 5, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille

Subjects
Male, Pathology, medicine.medical_specialty, Disease, β amyloid, mental disorders, medicine, Humans, Longitudinal Studies, Perivascular space, Aged, Aged, 80 and over, Amyloid beta-Peptides, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Odds ratio, Magnetic Resonance Imaging, Hyperintensity, Confidence interval, Peptide Fragments, Blood pressure, medicine.anatomical_structure, Cerebral Small Vessel Diseases, Female, Neurology (clinical), Small vessel, France, business, Biomarkers, Follow-Up Studies
Abstract

Objective: We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Methods: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Results: Low plasma Aβ 1–40 levels were associated with increased progression of WMH, and low Aβ 1–42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16–2.38). Consistently low Aβ 1–40 and Aβ 1–42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE e4 genotype. Conclusions: Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.

Published
2014

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