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1. How many patients are eligible for disease-modifying treatment in Alzheimer’s disease? A French national observational study over 5 years

Author: Didier Hannequin, Florence Pasquier, Bruno Dubois, David Wallon, Julien Dumurgier, Stéphane Epelbaum, Thérèse Jonveaux, Annick Besozzi, Stéphane Pouponneau, Caroline Hommet, Laetitia Berly, Adrien Julian, Marc Paccalin, Julie Bellet, Claire Boutoleau-Bretonniere, Thiphaine Charriau, Olivier Rouaud, Olivier Madec, Aurélie Mouton, Renaud David, Samir Bekadar, Roxane Fabre, and Walter Deberdt
Subjects: Medicine
Abstract: ObjectiveWe aimed to study the epidemiology of the prodromal and mild stages of Alzheimer’s disease (AD) patients who are eligible for clinical trials with disease-modifying therapies.SettingsWe analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists. Data from 2014 to 2018 have been analysed.ParticipantsPatients, 50–85 years old, diagnosed with AD who had an Mini-Mental State Exam (MMSE) score of ≥20 were included. We excluded patients with mixed and non-AD neurocognitive disorders.Primary outcome measureDescriptive statistics of the population of interest was the primary measure.ResultsIn the National Alzheimer Database, 550 198 patients were assessed. Among them, 72 174 (13.1%) were diagnosed with AD and had an MMSE ≥20. Using corrections for specificity of clinical diagnosis of AD, we estimated that about 50 000 (9.1%) had a prodromal or mild AD. In the combined electronic clinical records database of 11 French expert memory centres, a diagnosis of prodromal or mild AD, certified by the use of cerebrospinal fluid AD biomarkers, could be established in 195 (1.3%) out of 14 596 patients.ConclusionsAD was not frequently diagnosed at a prodromal or mild dementia stage in France in 2014 to 2018. Diagnosis rarely relied on a pathophysiological marker even in expert memory centres. National databases will be valuable to monitor early stage AD diagnosis efficacy in memory centres when a disease-modifying treatment becomes available.
Published: 2019
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2. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

Author: Hélène-Marie Lanoiselée, Gaël Nicolas, David Wallon, Anne Rovelet-Lecrux, Morgane Lacour, Stéphane Rousseau, Anne-Claire Richard, Florence Pasquier, Adeline Rollin-Sillaire, Olivier Martinaud, Muriel Quillard-Muraine, Vincent de la Sayette, Claire Boutoleau-Bretonniere, Frédérique Etcharry-Bouyx, Valérie Chauviré, Marie Sarazin, Isabelle le Ber, Stéphane Epelbaum, Thérèse Jonveaux, Olivier Rouaud, Mathieu Ceccaldi, Olivier Félician, Olivier Godefroy, Maite Formaglio, Bernard Croisile, Sophie Auriacombe, Ludivine Chamard, Jean-Louis Vincent, Mathilde Sauvée, Cecilia Marelli-Tosi, Audrey Gabelle, Canan Ozsancak, Jérémie Pariente, Claire Paquet, Didier Hannequin, Dominique Campion, and collaborators of the CNR-MAJ project
Subjects: Medicine
Abstract: BackgroundAmyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.Methods and findingsWe report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers-total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification.ConclusionsOur findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants.
Published: 2017
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3. Biomarker counseling, disclosure of diagnosis and follow‐up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey

Author: Mathieu Ceccaldi, Timo Grimmer, Vesna Jelic, Luiza Spiru, Pierre Jean Ousset, Stephanie Sloan, Marcel G. M. Olde Rikkert, Isabel Santana, Sebastiaan Engelborghs, Bruno Dubois, Milica G. Kramberger, David Robinson, Lucrezia Hausner, Latchezar Traykov, Mercè Boada, Robert Perneczky, Gunhild Waldemar, Alberto Lleó, Elisabet Sánchez, Thomas R. Nielsen, Tomasz Gabryelewicz, Olivier Rouaud, Nikolaos Scarmeas, Alexandre de Mendonça, Jacques Hugon, Kristian Steen Frederiksen, Bernard Hanseeuw, Lutz Frölich, Flavio Nobili, Görsev Yener, Mario Riverol, Ildebrando Appollonio, Audrey Gabelle, Birgitte Bo Andersen, Elka Stefanova, Katerina Sheardova, Jakub Hort, Anne M Koivisto, Thibaud Lebouvier, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Frederiksen, K, Nielsen, T, Appollonio, I, Andersen, B, Riverol, M, Boada, M, Ceccaldi, M, Dubois, B, Engelborghs, S, Frolich, L, Hausner, L, Gabelle, A, Gabryelewicz, T, Grimmer, T, Hanseeuw, B, Hort, J, Hugon, J, Jelic, V, Koivisto, A, Kramberger, M, Lebouvier, T, Lleo, A, de Mendonca, A, Nobili, F, Ousset, P, Perneczky, R, Olde Rikkert, M, Robinson, D, Rouaud, O, Sanchez, E, Santana, I, Scarmeas, N, Sheardova, K, Sloan, S, Spiru, L, Stefanova, E, Traykov, L, Yener, G, Waldemar, G, University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Universitat Internacional de Catalunya [Barcelona] (UIC), Instituto de Salud Carlos III [Madrid] (ISC), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Heidelberg University, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mossakowski Medical Research Centre (CMDIK), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospital Motol [Prague], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Karolinska University Hospital [Stockholm], University of Eastern Finland, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Ljubljana, Université de Lille, Hospital de la Santa Creu i Sant Pau, Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli studi di Genova = University of Genoa (UniGe), IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Ludwig-Maximilians University [Munich] (LMU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Imperial College London, Radboud University Medical Center [Nijmegen], St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), University of Coimbra [Portugal] (UC), National and Kapodistrian University of Athens (NKUA), Columbia University Irving Medical Center (CUIMC), St. Anne’s University Hospital [Brno], Ninewells Hospital and Medical School [Dundee], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University of Belgrade [Belgrade], and Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ)
Subjects: Counseling, Advance care planning, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], diagnosis, Disease, 0302 clinical medicine, Medicine, 030212 general & internal medicine, survey experiment, Cognitive decline, Cognitive impairment, Response rate (survey), diagnosis [Alzheimer Disease], Alzheimer's disease, 3. Good health, Europe, diagnosi, Psychiatry and Mental health, Disease Progression, biomarker, Biomarker (medicine), biomarker counseling, biomarkers, dementia, diagnostic disclosure, mild cognitive impairment, survey, medicine.medical_specialty, Referral, Neuroscience(all), Clinical Neurology, Disclosure, Sensitivity and Specificity, 03 medical and health sciences, Alzheimer Disease, Humans, Dementia, Cognitive Dysfunction, ddc:610, MED/26 - NEUROLOGIA, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, diagnosis [Cognitive Dysfunction], Family medicine, Human medicine, Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Contains fulltext : 231797.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.
Published: 2020

4. Meal-related difficulties and weight loss in older people: Longitudinal data from MAPT study

Author: Gaëlle Soriano, Philippe De Souto Barreto, Kelly Virecoulon Giudici, Christelle Cantet, Sophie Guyonnet, Bruno Vellas, Yves Rolland, Sandrine Andrieu, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Céline Caillaud, Pierre-Jean Ousset, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda Marie-Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Nicola Coley, Laboratoire de Gérontechnologie [Hôpital La Grave-CHU de Toulouse], 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)-Gérontopôle, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Vieillissement, MAPT DSA Study Group: Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda Marie-Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Sandrine Andrieu, Christelle Cantet, Nicola Coley, and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Gerontology, Male, Meal preparation, Weight loss, Activities of daily living, [SDV]Life Sciences [q-bio], Health Behavior, 030209 endocrinology & metabolism, (financial or non-financial) related to the study, Disease, Critical Care and Intensive Care Medicine, Body Mass Index, Preparing meals, 03 medical and health sciences, Eating, Food Preferences, 0302 clinical medicine, Cognition, Elderly, Shopping, medicine, Humans, Longitudinal Studies, Prospective Studies, Cooking, Meals, Aged, Randomized Controlled Trials as Topic, 2. Zero hunger, Aged, 80 and over, Meal, 030109 nutrition & dietetics, Nutrition and Dietetics, Proportional hazards model, business.industry, Depression, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Functional Status, Female, Independent Living, medicine.symptom, business
Abstract: International audience; BACKGROUND: Difficulties with meal-related activities (preparing meals and food shopping) may influence food intake, and contribute to nutritional risk among elderly people. All known studies on this topic had a cross-sectional design, thereby no causal relationships could be derived. We aim to investigate if difficulties with meal-related activities can contribute to subsequent weight loss in community-dwelling older people. METHODS: We used data of older subjects from the MAPT Study (n = 1531, median age = 74 years, 64% women), who provided prospective data on weight every 6 months and cognitive, physical condition, and functional capacities every year during a 3-year period. Difficulties preparing meals and shopping were evaluated each year with the Alzheimer's Disease Cooperative Study-Activities of Daily Living Prevention Instrument (ADCS ADL-PI) Scale. The risk of losing weight (≥5% or ≥ 3 kg in the following year) was estimated using a time-dependent Cox regression model. RESULTS: During the 3-year follow-up, a total of 851 subjects experienced at least a 5% or 3 kg weight loss. Two hundred thirty-seven subjects declared having difficulties with meal preparation at least once, and 133 declared having difficulties shopping. Subjects reporting any meal-related difficulties were older (p \textless 0.001), had more depressive symptoms (p \textless 0.001), and a lower physical function (p \textless 0.001) compared to those without difficulties. They also had a lower cognitive score (preparing meals: p \textless 0.001; shopping: p = 0.005) and a lower body mass index (preparing meals: p = 0.005; shopping: p = 0.023) at the end of the study. Meal-related activities were not associated with weight loss in unadjusted analysis and after adjustment for sex, age, depression, physical and cognitive status. CONCLUSION: Difficulties preparing meals and shopping had no effect on weight loss in community-dwelling older people, despite their association with advanced age, functional decline, and depressive symptoms.
Published: 2020

5. High Prevalence of Social Cognition Disorders and Mild Cognitive Impairment Long Term After Stroke

Author: Ariane Piver, Yannick Béjot, Anny Graule-Petot, Bénédicte Sensenbrenner, Sophie Guillemin, Agnès Jacquin-Piques, Olivier Rouaud, Maurice Giroud, Memory Centre, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Population, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Social cognition, Interquartile range, Prevalence, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Neuropsychological assessment, Social Behavior, education, Stroke, Aged, Aged, 80 and over, education.field_of_study, Rehabilitation, medicine.diagnostic_test, business.industry, Age Factors, Cognition, Middle Aged, medicine.disease, 3. Good health, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Physical therapy, Female, Geriatrics and Gerontology, Cognition Disorders, business, Gerontology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; PURPOSE: Social cognition disorders after stroke are poorly described. Yet, rehabilitation difficulties are frequent after stroke. This study aimed to evaluate the frequency of social cognition disorders 3 years after a first-ever stroke and to assess the factors associated with this condition. The second aim was to describe all the cognitive domains altered in the same population. METHODS: Patients who suffered from a first-ever ischemic or hemorrhagic stroke underwent clinical and neuropsychological assessment, which included the mini-Social cognition and Emotional Assessment (SEA) for evaluating social cognition. RESULTS: The 43 included patients were 67+/-15 years old, with a median Neurological Institute of Health Stroke Scale (NIHSS) (+/- interquartile range) at 0+/-1, and a median modified Rankin Scale (+/- interquartile range) at 1+/-1. Twenty patients (46.5%) had poor results in the facial emotions subtest; this factor was associated with a low educational grade (P=0.001). Fourteen patients (34.2%) had poor results on the "faux-pas" recognition subtest; this factor was associated with nonverbal episodic memory disorders (P=0.01). Thirty four patients (79.1%) had cognitive impairment, with at least 1 cognitive domain affected. CONCLUSIONS: The study demonstrates the high frequency of social cognition impairment 3 years after the first-ever stroke in young patients. Doctors and nurses should be sensitized to cognitive handicap after stroke because of difficulties for rehabilitation and returning to work.
Published: 2019

6. In the here and now: Short term memory predictions are preserved in Alzheimer's disease

Author: Audrey Mazancieux, Céline Souchay, Yannick Béjot, Olivier Rouaud, Julie M. F. Bertrand, Chris J. A. Moulin, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Bourgogne (UB), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, and Centre Leenaards de la mémoire
Subjects: Male, Cognitive Neuroscience, media_common.quotation_subject, Short-term memory, Experimental and Cognitive Psychology, behavioral disciplines and activities, 050105 experimental psychology, Task (project management), [SCCO]Cognitive science, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Metamemory, Memory span, medicine, Humans, 0501 psychology and cognitive sciences, Function (engineering), ComputingMilieux_MISCELLANEOUS, Aged, media_common, Memory Disorders, Working memory, Anosognosia, 05 social sciences, Awareness, Impaired memory, medicine.disease, Memory, Short-Term, Neuropsychology and Physiological Psychology, [SCCO.PSYC]Cognitive science/Psychology, Agnosia, Female, Metacognition, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: According to neuropsychological models of anosognosia, there is a failure to transfer on-line awareness of dysfunction into a more generalised long term belief about memory function in Alzheimer's disease. This failure results in specific metamemory deficits for global predictions: patients overestimate their performance before the task but are able to monitor their memory performance after having experienced the task. However, after a delay, they are still not able to make accurate predictions. As previous work has mainly focused on long-term memory, the present study investigates this issue in short-term and working memory. Using both global and item-by-item metacognitive judgements in a digit span task, we showed that Alzheimer's disease patients are as accurate as older adults in monitoring their performance despite impaired memory. When they have the opportunity to test themselves, or when they have already performed the task, patients are able to use feedback to adjust their metacognitive judgements. Overall, these results show that even for a relatively complex task, patients with Alzheimer's disease are aware of their difficulties in the here-and-now.
Published: 2019

7. Improving the Diagnosis of the Frontal Variant of Alzheimer's Disease with the DAPHNE Scale

Author: Catherine Thomas-Antérion, Amandine Pallardy, Elsa Lehingue, Jean-Benoit Hardouin, Hélène Courtemanche, Frédérique Etcharry-Bouyx, Sandra Jourdaa, Olivier Rouaud, Claire Boutoleau-Bretonnière, Hélène Mollion, Julien Gueniat, Cédric Bretonnière, Sophie Auriacombe, Laetitia Rocher, Maité Formaglio, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Perseveration, media_common.quotation_subject, Disease, Audiology, Neuropsychological Tests, frontotemporal dementia, 050105 experimental psychology, Neglect, scale, Cohort Studies, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, 0501 psychology and cognitive sciences, Apathy, behavioral disorders, media_common, Aged, business.industry, General Neuroscience, 05 social sciences, General Medicine, Middle Aged, medicine.disease, Frontal Lobe, Psychiatry and Mental health, Clinical Psychology, Disinhibition, Orbitofrontal cortex, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Geriatrics and Gerontology, medicine.symptom, Differential diagnosis, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Frontotemporal dementia, Research Article
Abstract: Background: The frontal variant of Alzheimer’s disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD). For fAD, there is some dissociation between the clinical frontal presentation and imaging and neuropathological studies, which do not always find a specific involvement of the frontal lobes. DAPHNE is a behavioral scale, which demonstrated excellent performance to distinguish between bvFTD and AD. Objective: The aim of the present study was to assess the reliability of this new tool to improve the clinical diagnosis of fAD. Methods: Twenty fAD patients and their caregivers were prospectively included and were compared with 36 bvFTD and 22 AD patients. Results: The three main behavioral disorders in the fAD patients were apathy, loss of empathy, and disinhibition. Three disorders were discriminant because they were less frequent and less severe in the fAD patients than in the bvFTD patients, namely hyperorality, neglect, and perseverations. This specific pattern of behavioral disorders was corroborated by SPECT or 18FDG PET-CT scan that showed that patients with fAD could have a medial frontal hypoperfusion, whereas in bvFTD patients the orbitofrontal cortex was the main involved region, with more diffuse hypoperfusion. Conclusion: We demonstrated that DAPHNE had good sensitivity and good specificity to discriminate between the three groups and in particular between fAD and bvFTD patients. DAPHNE is a quick tool that could help clinicians in memory clinics not only to differentiate bvFTD from typical AD but also from fAD.
Published: 2021

8. Biomarker counseling, disclosure of diagnosis, and follow‐up in patients with mild cognitive impairment: A European survey of EADC centers

Author: Alexandre de Mendonça, Timo Grimmer, Katerina Sheardova, Marcel G. M. Olde Rikkert, Jacques Hugon, Bruno Dubois, Anne M. Koivisto, Bernard Hanseeuw, Robert Perneczky, Ildebrando Apollonio, Lucrezia Hausner, Luiza Spiru, Audrey Gabelle, Birgitte Bo Andersen, Gunhild Waldemar, Stephanie Sloan, Görsev Yener, Jakub Hort, Flavio Nobili, Isabel Santana, Pierre Jean Ousset, David Robinson, Mathieu Ceccaldi, Kristian Steen Frederiksen, Sebastiaan Engelborghs, Tomasz Gabryelewicz, Olivier Rouaud, Rune Kristian Lundedal Nielsen, Nikolaos Scarmeas, and Latchezar Traykov
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Biomarker (medicine), Dementia, In patient, Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business, Cognitive impairment
Published: 2020

9. Associations Between Physical Activity, Blood-Based Biomarkers of Neurodegeneration, and Cognition in Healthy Older Adults: The MAPT Study

Author: Randall J. Bateman, Jean-Pierre Salles, Pascale Rebaudet, Jacques Touchon, Christian Carpuat, Claire Vinel, Dominique Dubois, Aurélia Romano, Flavien Terracol, Emeline Combrouze, Marc Bonnefoy, Philipe de Souto Barreto, Thierry Dantoine, Sylvie Caspar-Bauguil, Stéphane Chanalet, Marie-Laure Pader, Isabelle Saulnier, Sandrine Andrieu, Philippe Robert, Mapt, Céline Caillaud, Michèle Allard, Christelle Cantet, Pierre Payoux, Christine Malick-Loiseau, Sandrine Louchart, Nicola Coley, Lynda Touati, Françoise Hugon, Charlotte Dupuy, Alexandra Foubert, Olivier Rouaud, Kristel Sudres, Alain Bonafe, Geetika Aggarwal, Audrey Gabelle, Sophie Peiffer, Karim Bennys, Francine Fontaine, H. Villars, N. Costa, Evelyne Franon, Jean-François Dartigues, Jean-François Lefebvre, Carole Badufle, Sandrine Cerda, Catherine Burdet, Pierre Livet, Frédéric Ricolfi, Jean-François Mangin, Andrew D. Nguyen, Michael Li Yung Tong, Sylvie Chaillou, Lawrence Bories, Jérémy Raffin, Yan Li, Samira Misbah El Idrissi, Sophie Marilier, Nadège Barro-Belaygues, Bruno Vellas, Marie-Agnès Picat, Catherine Faisant, Françoise Desclaux, Bertrand Perret, Serge Bordes, Pierre-Jean Ousset, Laurent Molinier, Cécile Pays, Yves Rolland, Jean-Pierre Clément, Stéphanie Willebois, Patrick Manckoundia, Michel Zanca, Yannick Gasnier, Valérie Quipourt, Isabelle Carrié, Valérie Faure, Christophe Morin, Christophe Cognard, Claire Gédéon, Lauréane Brigitte, Colette Blatge, Julien Delrieu, Claire Gervais, Pascale Olivier-Abbal, Hélène Derumeaux, Carole Dufouil, Ali Bouhayia, Danièle Begorre, Alain Pesce, Marie Chupin, Françoise Lala, Fabrice Bonneville, Brigitte Gilbert, Franck Le Duff, Laurence Bernard-Bourzeix, Evelyne Cazaban-Campistron, Isabelle Marcet, Jacques Darcourt, François Cotton, Bruno Lapoujade, Gabor Abellan van Kan, John E. Morley, Sophie Guyonnet, Corinne Costes, Sebastien Gonfrier, Audrey Zueras, Anne Hitzel, Stéphanie Roth, Cecilia Marelli, Fleur Delva, Stéphane Lehéricy, Nicolas Lebrun, Pierre Skolil, Khaled Khales, Cécile Laubarie-Mouret, Jacques Monteil, Marie-France Basset, Thierry Voisin, François Chollet, Noëlle Cardinaud, Marie Paule Bonceour Martel, and Ileana Desormais
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Aging, Amyloid, Physical exercise, Neuropsychological Tests, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Cognition, Alzheimer Disease, Neurofilament Proteins, Internal medicine, Medicine, Humans, Cognitive Dysfunction, Cognitive decline, Correlation of Data, Exercise, Geriatric Assessment, Aged, Amyloid beta-Peptides, business.industry, Peptide Fragments, Cognitive test, 030104 developmental biology, Cross-Sectional Studies, Quartile, Concomitant, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Physical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of PA with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related to cognition. Four-hundred and sixty-five nondemented older adults engaged in an interventional study and who had a concomitant assessment of PA levels and blood measurements of NFL (pg/mL) and Aβ 42/40 were analyzed. A composite Z-score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500–999 and 2000+ MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with a lower probability of having high NFL concentrations (ie, ≥91.961 pg/mL [third quartile]). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ 42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ 42/40. Furthermore, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favorable relationship between PA and cognition. More investigations on non demented older adults are required for further validation of the present findings.
Published: 2020

10. Clinical Reasoning: A 69-year-old man with rare complex visual symptoms

Author: Renaud Du Pasquier, Alex Vicino, Olivier Rouaud, and Davide Strambo
Subjects: Male, medicine.medical_specialty, Evening, genetic structures, Alarm clock, media_common.quotation_subject, Vision Disorders, Audiology, Blindness, law.invention, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Humans, 030212 general & internal medicine, media_common, Aged, Clinical reasoning, Brain, Emergency department, Visual symptoms, Gaze, Magnetic Resonance Imaging, eye diseases, Visual field, Feeling, Neurology (clinical), Psychology, 030217 neurology & neurosurgery
Abstract: A 69-year-old man was admitted from the emergency department of our hospital for subacute onset of visual complaints. The evening before admission, around 10 pm, while watching TV, he experienced binocular and persistent discomposed colors in the lower left visual field (appearing both inside and outside the television screen) that did not change with the direction of gaze. He went to bed and woke up at 1 am for usual nocturia; then, trying to read his alarm clock, he was unable to understand what time it was despite correctly seeing the numbers. He did not report other visual difficulties at that moment. When he woke again at 3 am, he had the impression he could not correctly define his position in space and, returning to bed, bumped into a lamp and had the feeling that his head went inside the lamp. At 5 am, waking up again, he found he was completely blind.
Published: 2020

11. Lipid Biomarkers in Alzheimer's Disease

Author: Gérard Lizard, Mohamed Hammami, Amira Zarrouk, Mohamed El Ayeb, Thibault Moreau, Mustapha Cherkaoui-Malki, Meryam Debbabi, El Mostafa Karym, Boubker Nasser, Asmaa Badreddine, Maryem Bezine, Olivier Rouaud, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Monastir - University of Monastir (UM), Université de Sousse, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Université Hassan 1er [Settat], The work on lipid biomarkers carried out by the team ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ EA7270 / Univ. Bourgogne Franche-Comté / INSERM is financially supported by: INSERM, Université de Bourgogne, ASSAD (Louhans, France), Department of Neurology (University Hospital, Dijon, France), Memory Center, Resources and Research of Burgundy (CMRR / University Hospital, Dijon, France), and Association pour le Développement des Sciences Neurologiques en Bourgogne (ADSNB, Dijon, France) and Association Bourguignonne pour les Applications des Sciences de l'Information en Médecine (ABASIM, Dijon, France). This work was also supported by grants from: Univ. Monastir (Monastir, Tunisia), Univ. El Manar (Tunis, Tunisia), Pasteur Institut (Tunis, Tunisia), Action Intégrée of the Comité Mixte Inter-Universitaire Franco-Marocain (CMIFM, AIMA/14/310, EGIDE) from the PHC Volubilis/Toubkal program, Ministère des Affaires Etrangères, Conseil Régional de Bourgogne, Ministère de l’enseignement et de la Recherche and Projet Sectoriel CNRST.
Subjects: 0301 basic medicine, medicine.medical_specialty, Lipid Metabolism Disorder, Amyloid, phospholipids, [SDV]Life Sciences [q-bio], Biology, fatty acids, lipids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Animals, Humans, Dementia, MESH: Animals, MESH: Lipid Metabolism, MESH: Humans, Cholesterol, biomarkers, cholesterol, Lipid metabolism, Peroxisome, Lipid Metabolism, medicine.disease, MESH: Lipids, 3. Good health, 030104 developmental biology, Endocrinology, Neurology, chemistry, Docosahexaenoic acid, Alzheimer, MESH: Biomarkers, oxysterols, lipids (amino acids, peptides, and proteins), Neurology (clinical), Alzheimer's disease, MESH: Alzheimer Disease, 030217 neurology & neurosurgery
Abstract: Background: There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer’s disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease. Methods: A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed. Results: Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage. Conclusion: There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.
Published: 2018

12. RETRACTED ARTICLE: Omega-3 fatty acid levels in red blood cell membranes and physical decline over 3 years: longitudinal data from the MAPT study

Author: Philipe De Souto Barreto, Marc Bonnefoy, Matteo Cesari, Francois Cotton, PERRET Bertrand, Olivier Rouaud, Pierre Payoux, Fleur Delva, Christophe Cognard, and Pascale OLIVIER
Subjects: 0301 basic medicine, 2. Zero hunger, chemistry.chemical_classification, Aging, medicine.medical_specialty, 030109 nutrition & dietetics, Fatty acid, Eicosapentaenoic acid, 03 medical and health sciences, Grip strength, 0302 clinical medicine, Geography, Quartile, chemistry, Docosahexaenoic acid, Internal medicine, Physical therapy, medicine, 030212 general & internal medicine, Geriatrics and Gerontology, Omega 3 fatty acid, Body mass index, Polyunsaturated fatty acid
Abstract: Studies have shown that omega-3 polyunsaturated fatty acids (PUFAs) are associated with brain, cardiovascular, and immune function, as well as physical performance and bone health in older adults. So far, few studies have investigated the associations between PUFA status and performance-based tests of physical function. The objective of this study was to investigate the associations between the omega-3 PUFA levels (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) in red blood cell (RBC) membranes and physical performance, in a sample of community-dwelling older adults. This is a longitudinal observational study using data from the Multidomain Alzheimer's Disease Trial (MAPT), a randomized, placebo-controlled trial. Four hundred participants from MAPT placebo group with available PUFA data were included. Omega-3 PUFA levels in RBC membranes were measured at baseline, and their percentage of total RBC membrane fatty acid content was calculated. We dichotomized the standardized omega-3 PUFA levels in RBC membranes as low (lowest quartile) vs. high (three upper quartiles). Gait speed (in m/s) and short physical performance battery (SPPB) score (range from 0 to 12, higher is better) were used to assess physical performance at baseline and after 6, 12, 24, and 36 months. Participants were 75.2 (± 4.3) years old and 68% were female. Bivariate analyses found that the characteristic of the participants in the lowest quartile of omega-3 PUFA levels (Q1) and those in the three upper quartiles (Q2-Q4) was not different at baseline; only those in Q1 were slightly older. In an unadjusted model, the difference in gait speed after 3 years of follow-up was significant (- 0.09 ± 0.03 m/s; p = 0.008) between participants in Q1 and those in Q2-Q4. In a model adjusted for age, gender, educational level, cognitive function, depressive status, body mass index, physical activity, grip strength, and their time interaction, this difference remained clinically relevant (- 0.07 ± 0.04 m/s; p = 0.075). No difference between the two groups was found for the SPPB score development over 3 years. Older adults with subjective memory complaints and in the lower quartile of omega-3 have a faster decline on gait speed compared to people in the three upper quartiles. Other longitudinal studies are needed to explore this association and to examine mechanisms.
Published: 2017

13. Cross-sectional associations of cortical β-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints

Author: Claire Vinel, Philipe De Souto Barreto, Francois Cotton, PERRET Bertrand, Olivier Rouaud, Pierre Payoux, Fleur Delva, Christophe Cognard, Pascale OLIVIER, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Adult, Male, 0301 basic medicine, Apolipoprotein E, Amyloid, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Linoleic acid, Apolipoprotein E4, Subjective memory, Biology, Placebo, Biochemistry, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Cognition, 0302 clinical medicine, Memory, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, chemistry.chemical_classification, Aniline Compounds, Erythrocyte Membrane, Middle Aged, Erythrocyte membrane, 030104 developmental biology, Endocrinology, chemistry, Fatty Acids, Unsaturated, Ethylene Glycols, Female, Arachidonic acid, 030217 neurology & neurosurgery, Polyunsaturated fatty acid
Abstract: Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical β-amyloid (Aβ) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial (MAPT) placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [18F] florbetapir positron emission tomography (PET). Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aβ and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aβ and erythrocyte membrane arachidonic acid (No apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01,0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00,0.06; p = 0.04) and Aβ and erythrocyte membrane linoleic acid (No apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04,0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04,0.00; p = 0.09). Furthermore, the association between Aβ and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E e4 non-carriers (B-coefficient 0.03, CI: 0.00,0.06, p = 0.03, n=36). In contrast, no association was found between Aβ and erythrocyte membrane linoleic acid in Apolipoprotein E e4 stratified analysis. Investigating the relationships between Aβ and PUFAs longitudinally would provide evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aβ-dependent mechanisms. This article is protected by copyright. All rights reserved.
Published: 2017

14. Effectiveness of a Standardized and Specific Follow-Up in Memory Centers in Patients with Alzheimer’s Disease

Author: Laure Rouch, Philippe Cestac, Charlene Cool, Catherine Helmer, Jean-Francois Dartigues, Claudine Berr, Olivier Rouaud, Bruno Vellas, Sandrine Andrieu, and null the REAL-FR Study Group and the 3C Study Group
Subjects: Male, 0301 basic medicine, Gerontology, Pediatrics, medicine.medical_specialty, Population, Kaplan-Meier Estimate, Disease, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Dementia, Prospective Studies, Treatment Failure, education, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, Mini–Mental State Examination, medicine.diagnostic_test, Proportional hazards model, business.industry, Hazard ratio, Cognition, medicine.disease, Confidence interval, 030104 developmental biology, Socioeconomic Factors, Neurology, Multivariate Analysis, Linear Models, Female, France, Neurology (clinical), Mental Status Schedule, Superior Sagittal Sinus, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objectives: To compare the 4-year survival, institutionalization, cognitive and functional decline of Alzheimer’s patients with specific follow-up in memory centers versus usual care. Design: Four year longitudinal follow-up. Settings: The French Network of memory centers in Alzheimer’s disease (REAL-FR study) and The French population-based study (3C study). Participants: 728 patients aged ≥ 65, living at home, meeting criteria for probable Alzheimer’s disease and having Mini Mental State Examination (MMSE) scores between 10 and 26 at baseline were included. Measurements: Cox proportional hazards models were performed to test the effectiveness of a specific follow-up in memory centers (REAL-FR study) versus usual care (3C study) on the 4-year survival and institutionalization. Linear mixed models were used to assess cognitive and functional decline in both groups. Results: After adjustment for confounding factors, the 4-year survival did not differ significantly between patients followed-up in memory centers and those who had recourse to usual care (usual care: Hazard Ratio adjusted (HRa) = 0.87, 95% confidence interval (CI) 0.53-1.43, p=0.59). Patients with a specific follow-up in memory centers had a higher risk of being institutionalized (usual care: HRa = 0.24, 95% CI 0.12-0.48, p Conclusion: Our findings failed to demonstrate any potential benefits of a specific follow-up in memory centers on clinically meaningful outcomes in the natural history of Alzheimer’s disease. Recourse to care in memory centers may have been the consequence of a faster dementia progression and a greater burden of Alzheimer’s disease, all leading to detrimental consequences on various prognostic outcomes.
Published: 2017

15. Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer’s Disease Before 51 Years

Author: Aline Zarea, Eloi Magnin, Stéphane Epelbaum, Claire Paquet, Valérie Chauviré, Florence Pasquier, Anne Boland, Marie Sarazin, David Wallon, Bruno Salomon, Dominique Campion, Olivier Godefroy, Olivier Martinaud, Mathilde Sauvée, Sophie Auriacombe, Cecilia Marelli, Frédérique Etcharry-Bouyx, Gaël Nicolas, Jean-François Deleuze, Anne-Claire Richard, Vincent de la Sayette, Audrey Gabelle, Thérèse Rivasseau Jonveaux, Stéphane Rousseau, Jérémie Pariente, Mathieu Ceccaldi, Maïté Formaglio, Anne Rovelet-Lecrux, Didier Hannequin, Adeline Rollin-Sillaire, Bernard Croisile, Isabelle Le Ber, Morgane Lacour, Olivier Quenez, Olivier Rouaud, Muriel Quillard-Muraine, Claire Boutoleau-Bretonnière, 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), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Rouen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), 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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Hospices Civils de Lyon (HCL), 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 Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), 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), 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), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and 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)
Subjects: 0301 basic medicine, Male, MESH: Mutation, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, MESH: Whole Exome Sequencing, Alzheimer Disease, Risk Factors, MESH: Risk Factors, MESH: Amyloid beta-Protein Precursor, PSEN2, Genotype, Genetic variation, Presenilin-2, Exome Sequencing, medicine, PSEN1, Presenilin-1, Humans, Early-onset Alzheimer's disease, Genetic Predisposition to Disease, Risk factor, Allele, Exome sequencing, Genetics, MESH: Humans, MESH: Middle Aged, business.industry, General Neuroscience, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, medicine.disease, MESH: Presenilin-1, MESH: Male, 3. Good health, MESH: Presenilin-2, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Female, Geriatrics and Gerontology, business, MESH: Female, 030217 neurology & neurosurgery, MESH: Alzheimer Disease
Abstract: International audience; Background:Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer’s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.Objective:To describe the proportion of each genetic variation among patients with very young-onset sporadic AD. Methods:We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved. Results:Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset (p
Published: 2019

16. Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials

Author: Noëlle Cardinaud, Francine Fontaine, Marie Paule Bonceour Martel, Danièle Begorre, Claire Vinel, Dominique Dubois, Serge Bordes, Charlotte Dupuy, Jean-François Dartigues, Lars Bäckman, Marie-Laure Pader, Colette Blatge, Jacques Touchon, Julien Delrieu, Karim Bennys, Miia Kivipelto, Pierre Payoux, Christian Vincent, Ileana Desormais, Françoise Hugon, Isabelle Saulnier, Michèle Allard, Pascale Olivier-Abbal, Patrick Manckoundia, Audrey Gabelle, Yannick Gasnier, Olivier Rouaud, Christine Malick-Loiseau, Carole Badufle, Christian Carpuat, Sophie Marilier, Sophie Peiffer, Stéphane Chanalet, Riitta Antikainen, Jean-Pierre Salles, Stéphanie Roth, Catherine Burdet, Pierre Livet, Nadège Barro-Belaygues, François Cotton, Tiia Ngandu, Pim van Gool, Alexandra Foubert, Eric P. Moll van Charante, Khaled Khales, Pierre-Jean Ousset, Hilkka Soininen, Valérie Faure, Sandrine Andrieu, Corinne Costes, Marie-Noelle-Cuffi, Frédéric Ricolfi, Pascale Rebaudet, Samira Misbah El Idrissi, Céline Caillaud, Marie Chupin, Alain Pesce, Françoise Lala, N. Costa, Emeline Combrouze, Carol Brayne, Bertrand Fougère, Michel Zanca, H. Villars, Sebastien Gonfrier, Fabrice Bonneville, Lynda Touati, Sandrine Cerda, Katri Hemio, Esko Levälahti, Jacques Darcourt, Philippe Robert, Christophe Morin, Brigitte Gilbert, Alain Bonafe, Catherine Faisant, Jacques Monteil, Lawrence Bories, Bram van de Groep, Edo Richard, Gabor Abellan van Kan, Valérie Quipourt, Marc Bonnefoy, Françoise Desclaux, Kristelle Sudres, Thierry Voisin, Timo E. Strandberg, Yves Rolland, Evelyne Franon, Susan Jongstra, Anna Stigsdotter-Neely, Marie-France Basset, Thierry Dantoine, Laurent Molinier, Tiina Laatikainen, Audrey Zueras, Jean-François Lefebvre, Claire Gédéon, Christelle Cantet, Jean-Pierre Clément, Jean-François Mangin, Aurélia Romano, François Chollet, Tuomo Hänninen, Yannick Meiller, Marie-Agnès Picat, Satu Havulinna, Tessa van Middelaar, Jenni Lehtisalo, Isabelle Marcet, Stéphanie Willebois, Christophe Cognard, Hélène Derumeaux, Cécile Pays, Laurence Bernard-Bourzeix, Sylvie Belleville, Anne Hitzel, Cathrien Beishuizen, Ali Bouhayia, Sylvie Chaillou, Bruno Lapoujade, Franck Le Duff, Bruno Vellas, Michael Li Yung Tong, Marieke P. Hoevenaar-Blom, Cecilia Marelli, Rainer Rauramaa, Flavien Terracol, Marko Gronholm, Fleur Delva, Mariagnese Barbera, Sandrine Louchart, Isabelle Carrié, Lauréane Brigitte, Alina Solomon, Bertrand Perret, Claire Gervais, Jaakko Tuomilehto, Carole Dufouil, Sherry L. Willis, Lennard L. van Wanrooij, Cécile Laubarie-Mouret, Nicolas Lebrun, Pierre Skolil, Francesca Mangiasche, Stéphane Lehéricy, Sophie Guyonnet, Jaana Lindström, Evelyne Cazaban-Campistron, Markku Peltonen, Antti Jula, Juliette Guillemont, Nicola Coley, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Karolinska Institutet [Stockholm], University of Helsinki, Faculty of Health Sciences [UEF, Kuopio, Finland], University of Eastern Finland, Vrije Universiteit Amsterdam [Amsterdam] (VU), Nijmegen Medical Centre [Nijmegen], Centre d'investigation clinique de Toulouse (CIC 1436), 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 Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), General practice, Public and occupational health, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Aging & Later Life, Graduate School, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CCSD, Accord Elsevier, Department of Public Health, Oral and Maxillofacial Surgery, Department of Medicine, Timo Strandberg / Principal Investigator, and HUS Internal Medicine and Rehabilitation
Subjects: Epidemiology, LIFE-STYLE INTERVENTIONS, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychological intervention, 3124 Neurology and psychiatry, Trial, 0302 clinical medicine, Risk Factors, Outcome Assessment, Health Care, 030212 general & internal medicine, PREDICTORS, Cognitive impairment, Finland, Depression (differential diagnoses), Clinical Trials as Topic, Health Policy, DEPRESSION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cognitive training, Exercise Therapy, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Female, medicine.medical_specialty, DISABILITY FINGER, Physical activity, Intervention, Placebo, EXERCISE ADHERENCE, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Intervention (counseling), Fatty Acids, Omega-3, medicine, Humans, Dementia, OLDER-ADULTS, Life Style, Aged, Cognitive Behavioral Therapy, business.industry, Prevention, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 3112 Neurosciences, COGNITIVE IMPAIRMENT, medicine.disease, Multidomain, FINNISH GERIATRIC INTERVENTION, PHYSICAL-ACTIVITY, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adherence, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Published: 2019

17. How many patients are eligible for disease-modifying treatment in Alzheimer’s disease? A French national observational study over 5 years

Author: Frédéric Blanc, Adrien Julian, Julie Bellet, Julien Dumurgier, Claire Boutoleau-Bretonnière, Renaud David, David Wallon, Jacques Hugon, P. Robert, Emmanuelle Liegey, Aurélie Mouton, Florence Pasquier, Claire Paquet, Samir Bekadar, Marc Paccalin, Stéphane Epelbaum, Didier Hannequin, Thérèse Rivasseau Jonveaux, Annick Besozzi, Bruno Dubois, Caroline Hommet, Roxane Fabre, Laetitia Berly, Olivier Madec, Walter Deberdt, Tiphaine Charriau, Olivier Rouaud, Stéphane Pouponneau, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), 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 [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], National Reference Center for Rare or Early Dementias and Center of Excellence of Neurodegenerative Disease (CoEN), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de gériatrie [Poitiers], Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nice (CHU Nice), 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 [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Eli Lilly and Company [Indianapolis], 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), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence sur les démences rares et maladie de Pick, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Département de neurologie [Lille], 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), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Charles Nicolle [Rouen], Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Centres Mémoire de Ressources et de Recherche [CHRU Nancy] (CMRR de Lorraine), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de Gériatrie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de jour St François [Strasbourg], Hôpital de la Milétrie, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Service de neurologie 1 [CHU Pitié-Salpétrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Epelbaum, Stéphane
Subjects: Male, Pediatrics, medicine.medical_specialty, Population, Prodromal Symptoms, Disease, 03 medical and health sciences, mild cognitive impairment, 0302 clinical medicine, Alzheimer Disease, Epidemiology, medicine, Humans, 030212 general & internal medicine, Stage (cooking), education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Research, prodromal Alzheimer’s disease, Incidence (epidemiology), General Medicine, Middle Aged, Mental Status and Dementia Tests, 3. Good health, Clinical trial, Databases as Topic, Neurology, mild Alzheimer’s disease, [SCCO.PSYC]Cognitive science/Psychology, Medicine, Female, epidemiology, National database, Observational study, France, business, Neurocognitive, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveWe aimed to study the epidemiology of the prodromal and mild stages of Alzheimer’s disease (AD) patients who are eligible for clinical trials with disease-modifying therapies.SettingsWe analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists. Data from 2014 to 2018 have been analysed.ParticipantsPatients, 50–85 years old, diagnosed with AD who had an Mini-Mental State Exam (MMSE) score of ≥20 were included. We excluded patients with mixed and non-AD neurocognitive disorders.Primary outcome measureDescriptive statistics of the population of interest was the primary measure.ResultsIn the National Alzheimer Database, 550 198 patients were assessed. Among them, 72 174 (13.1%) were diagnosed with AD and had an MMSE ≥20. Using corrections for specificity of clinical diagnosis of AD, we estimated that about 50 000 (9.1%) had a prodromal or mild AD. In the combined electronic clinical records database of 11 French expert memory centres, a diagnosis of prodromal or mild AD, certified by the use of cerebrospinal fluid AD biomarkers, could be established in 195 (1.3%) out of 14 596 patients.ConclusionsAD was not frequently diagnosed at a prodromal or mild dementia stage in France in 2014 to 2018. Diagnosis rarely relied on a pathophysiological marker even in expert memory centres. National databases will be valuable to monitor early stage AD diagnosis efficacy in memory centres when a disease-modifying treatment becomes available.
Published: 2019

18. Reduced Regional Cortical Thickness Rate of Change in Donepezil-Treated Subjects With Suspected Prodromal Alzheimer’s Disease

Author: Marie Chupin, Enrica Cavedo, Marie Sarazin, Guy Louis Tisserand, Florence Pasquier, Nadine Girard, Olivier Rouaud, Harald Hampel, Samantha Galluzzi, Alain Vighetto, Didier Dormont, Bruno Dubois, Simone Lista, Christine Delmaire, Olivier Colliot, Alain Bonafe, Stéphane Lehéricy, Bernard Croisile, Frédéric Ricolfi, Mathieu Ceccaldi, Françoise Duveau, Jacques Touchon, Pierre-Jean Ousset, Université Pierre et Marie Curie - Paris 6 (UPMC), 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), 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), Algorithms, models and methods for images and signals of the human brain (ARAMIS), 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], 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)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Casselardit - Junod, Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), IRCCS Fatebenefratelli - Brescia, Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), IEF, Université Paris-Sud - Paris 11 (UP11), Eisai, CHU Saint-Antoine [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], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (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 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)-Inria de Paris, Service de Neuroradiologie [CHU Pitié-Salpêtrière], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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 National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, and Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV]
Subjects: Male, 0301 basic medicine, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, law.invention, 0302 clinical medicine, Piperidines, Randomized controlled trial, law, Outcome Assessment, Health Care, Donepezil, Longitudinal Studies, Nootropic Agents, Aged, 80 and over, Cerebral Cortex, medicine.diagnostic_test, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Cerebral cortex, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Indans, Disease Progression, Cardiology, Female, Alzheimer's disease, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, medicine.drug, medicine.medical_specialty, Prodromal Symptoms, Placebo, 03 medical and health sciences, Double-Blind Method, Alzheimer Disease, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Dementia, Cognitive Dysfunction, Aged, Surrogate endpoint, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Amnesia, Neuroscience, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day). The study started in November 2006 and concluded in August 2010. All subjects underwent 2 brain structural magnetic resonance imaging (MRI) scans, at baseline and at the end of the trial. Structural MRI images had been processed using the automated pipeline for longitudinal segmentation and surface reconstruction implemented in FreeSurfer. The primary outcome measure of this post hoc study was the annualized percentage change (APC) of cortical thickness. RESULTS: The donepezil group exhibited reduced APC cortical thinning compared to placebo in the rostral anterior cingulate (right: P = .048; left: P = .032), the orbitofrontal (right: P = .012; left: P < .048), and the right inferior frontal (P = .022) cortices and in the right insula (P = .010). These results were not statistically significant after Bonferroni correction likely due to insufficient power for cortical thickness measurements in the study group powered for the predefined hippocampus outcome. CONCLUSIONS: Our findings support the hypothesis that cortical thickness is a reliable candidate surrogate outcome in early predementia AD trials. In addition, donepezil treatment may have an impact on cortical structure/morphology in areas innervated by the medial and lateral cholinergic pathways. BACKGROUND: ClinicalTrials.gov identifier: NCT00403520. 77
Published: 2016

19. Gender effect on driving cessation in pre-dementia and dementia phases: results of the 3C population-based study

Author: Bernard Laumon, Catherine Helmer, Olivier Rouaud, Sophie Auriacombe, Colette Fabrigoule, Sylviane Lafont, Claudine Berr, and Laetitia Marie Dit Asse
Subjects: Gerontology, Cognition, medicine.disease, Population based study, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Gender effect, Cohort, medicine, Dementia, 030212 general & internal medicine, Geriatrics and Gerontology, Driving cessation, Prospective cohort study, Psychology, 030217 neurology & neurosurgery
Abstract: Objectives: Aging entails deterioration in sensory, physical, and cognitive functions, raising doubt in the driving capacity of older drivers, especially when the deficits are severe, as in dementia. Many older drivers, especially women, adapt their driving habits in order to compensate for these deficits and eventually stop driving. The present prospective study assessed driving cessation in men and women throughout the dementia process, including a 2-year pre-dementia phase. Methods: The study was based on a three-city cohort of subjects who were aged 65 years and older in 2000 and followed for more than 10 years. Active dementia detection was conducted at each followup. The probability of driving cessation was assessed in men and women during the 2-year predementia phase and until 5 years after diagnosis. Results: In the 2-year pre-dementia phase, both men and women ceased driving earlier than drivers with no central nervous system pathology (p
Published: 2016

20. Semantic memory assessment in 15 patients with amyotrophic lateral sclerosis

Author: Olivier Rouaud, A. Graule Petot, Marie Hervieu-Bègue, A. Catteau, and M. Giroud
Subjects: Adult, Male, medicine.medical_specialty, Semantic dementia, Disease, Neuropsychological Tests, Audiology, Severity of Illness Index, 050105 experimental psychology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Memory, Severity of illness, medicine, Humans, Verbal fluency test, Semantic memory, 0501 psychology and cognitive sciences, Amyotrophic lateral sclerosis, Aged, Aged, 80 and over, Memory Disorders, business.industry, Amyotrophic Lateral Sclerosis, 05 social sciences, Neuropsychology, Cognition, Middle Aged, medicine.disease, Semantics, Neurology, Female, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Introduction A total of 30 to 50% of amyotrophic lateral sclerosis patients suffer from cognitive disorders. The aim of the study is to characterize these disorders and to assess semantic memory in non-demented ALS patients. The secondary aim is to look for a link between disease type and neuropsychological characteristics. Method Patients were followed in an ALS center in Dijon. The following neuropsychological tests were used in this study: Folstein test, BREF test, verbal fluency, Isaac test, GRESEM test and TOP 30 test. Results Fifteen ALS patients were included. Nine of them (60%) were suffering from a semantic memory disorder. There was no correlation between ALS characteristics and the semantic memory disorder. Discussion This is the first study to reveal a semantic memory disorder in ALS. This result accentuates the hypothesis that ALS and semantic dementia are two phenotypes of the same degenerative process linked to TDP 43 proteinopathy.
Published: 2016

21. Combined microwave processing and enzymatic proteolysis of bovine whey proteins: the impact on bovine β-lactoglobulin allergenicity

Author: Hanitra Rabesona, Sébastien Curet, Colette Larré, Kamel Eddine El Mecherfi, Thomas Haertlé, Roberta Lupi, Olivier Rouaud, Yvan Choiset, Laboratoire de Physiologie de la Nutrition et Sécurité Alimentaire, Département de Biologie, Faculté des Sciences, Université Oran 1 Ahmed Ben Bella, Optimisation - Système - Energie (GEPEA-OSE), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), UMR1268, Biopolymères, Interactions Assemblages (BIA), Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN), and Region Pays de la Loire-France
Subjects: Whey protein, Globulin, Proteolysis, Thermal process, Basophil degranulation, Hydrolysate, Whey protein isolate, 03 medical and health sciences, 0404 agricultural biotechnology, Enzymatic hydrolysis, medicine, Pepsin, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Microwaves, Beta-lactoglobulin, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Chromatography, beta-Lactoglobulin, biology, medicine.diagnostic_test, Chemistry, Allergen, food and beverages, 04 agricultural and veterinary sciences, 040401 food science, Specific IgE, biology.protein, Original Article, Food Science
Abstract: International audience; The main aim of this study was to develop a continuous microwave treatment system of whey proteins and then apply this process at 37 degrees C, 50 degrees C, 65 degrees C and 70 degrees C to achieve pepsinolysis and produce extensively hydrolysed bovine whey protein hydrolysates with low allergenic properties. The microwave process was compared to a conventional thermal treatment with similar temperature set points. Both processes were deeply analysed in terms of the thermal kinetics and operating conditions. The pepsin hydrolysates obtained by the continuous microwave treatment and conventional heating were characterized by SDS-PAGE and RP-HPLC. The allergenicity of the whey protein hydrolysates was explored using a human IgE sensitized rat basophil leukaemia cell assay. The results indicate that extensively hydrolysed whey protein hydrolysates were obtained by microwave only at 65 degrees C and in a shorter time compared with the conventional thermal treatment. In the same temperature conditions under conventional heating, -lactoglobulin was resistant to pepsinolysis, and 37% of it remained intact. As demonstrated by an in vitro degranulation assay using specific human IgE-sensitized rat basophils, the extensively hydrolysed whey protein obtained by microwave showed maximum degranulation values of 6.53% compared to those of the native whey protein isolate (45.97%) and hence elicited no more allergenic reactions in basophils. This work emphasizes the potential industrial use of microwave heating specific to milk protein processing to reduce their allergenicity and improve their end-use properties.
Published: 2018

22. Temporal trends in the premorbid use of preventive treatments in patients with acute ischemic cerebrovascular events and a history of vascular disease: The Dijon Stroke Registry (1985–2010)

Author: Cécile Chazalon, Yannick Béjot, Olivier Rouaud, Catherine Vergely, Guy-Victor Osseby, Catia Khoumri, Marie Hervieu-Bègue, Christelle Blanc, Jérôme Durier, Maurice Giroud, Benoit Delpont, Benoit Daubail, Henri Bailly, Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), and Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, Pediatrics, medicine.medical_specialty, Stroke registry, Time Factors, Population, Coronary Artery Disease, Disease, 030204 cardiovascular system & hematology, Logistic regression, Coronary artery disease, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Secondary Prevention, medicine, Humans, In patient, Prospective Studies, Registries, education, Antihypertensive Agents, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Secondary prevention, education.field_of_study, Vascular disease, business.industry, General Medicine, Middle Aged, medicine.disease, 3. Good health, Stroke, Female, France, business, 030217 neurology & neurosurgery
Abstract: Although secondary prevention in patients with arterial vascular diseases has improved, a gap between recommendations and clinical practice may exist.We aimed to evaluate temporal trends in the premorbid use of preventive treatments in patients with ischemic cerebrovascular events (ICVE) and prior vascular disease.Patients with acute ICVE (ischemic stroke/TIA) were identified through the population-based stroke registry of Dijon, France (1985-2010). Only those with history of arterial vascular disease were included and were classified into four groups: patients with previous coronary artery disease only (CAD), previous peripheral artery disease only (PAD), previous ICVE only, and patients with at least two different past vascular diseases (polyvascular group). We assessed trends in the proportion of patients who were treated with antihypertensive treatments and antithrombotics at the time of their ICVE using multivariable logistic regression models.Among the 5309 patients with acute ICVE, 2128 had a history of vascular disease (mean age 77.3±11.9, 51% men; 25.1% CAD 7.5% PAD, 39.8% ICVE, and 27.5% poylvascular). A total of 45.8% of them were on antithrombotics, 64.1% on antihypertensive treatment, and 34.4% on both. Compared with period 1985-1993, periods 1994-2002 and 2003-2010 were associated with a greater frequency of prior-to-ICVE use of antithrombotics (adjusted OR=5.94; 95% CI: 4.61-7.65, P0.01, and adjusted OR=6.92; 95% CI: 5.33-8.98, P0.01, respectively) but not of antihypertensive drugs. Consistent results were found when analyses were stratified according to the type of history of arterial vascular disease.Patients with ICVE and previous vascular disease were still undertreated with recommended preventive therapies.
Published: 2017

23. Physical Activity and Amyloid-β Brain Levels in Elderly Adults with Intact Cognition and Mild Cognitive Impairment

Author: Claire Vinel, Philipe De Souto Barreto, Marc Bonnefoy, Francois Cotton, PERRET Bertrand, Olivier Rouaud, Pierre Payoux, Christophe Cognard, Daviet, Jean-Christophe, Géosciences Paris Sud ( GEOPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Eugène Marquis ( CRLCC ), Epidémiologie et anlyses en santé publique: risques, maladies chroniques et handicaps, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Géosciences Paris Sud (GEOPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, Oncology, Gerontology, Apolipoprotein E, medicine.medical_specialty, Multivariate analysis, Amyloid, Physical activity, Standardized uptake value, Motor Activity, Cognition, Alzheimer Disease, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Humans, Medicine, Dementia, Cognitive Dysfunction, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Brain, medicine.disease, Cross-Sectional Studies, Positron emission tomography, Positron-Emission Tomography, Female, Geriatrics and Gerontology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives To examine the associations between amyloid-β brain deposition and physical activity (PA) in elderly adults without dementia and to investigate whether the association has a dose-response relationship. Design Cross-sectional study. Setting French community-dwelling people. Participants Elderly adults with normal or mildly impaired cognition (mean age 74.7 ± 4.2; 60.4% female) with available information on current self-reported PA and amyloid-β brain deposition measured using positron emission tomography (PET) using the PET-ligand florbetapir F 18 (n = 268). Measurements A standardized uptake value ratio (SUVR) was obtained for each subject. Participants were divided according to amyloid plaque cortical retention defined according to a SUVR cutoff of 1.10 (SUVR+ vs SUVR−). Results Bivariate and multivariate analyses showed that PA was not significantly associated with SUVR. SUVR+ and SUVR− participants did not differ in terms of volume (continuous PA variables) and levels (categorical PA variables) of PA. PA was not correlated with SUVR in apolipoprotein E e4 carriers or noncarriers. PA was not associated with cognitive function. Conclusion Although PA protects against dementia, there is no solid evidence that this protection involves a reduction in amyloid-β brain deposition. Further studies are needed to determine whether PA (ideally measured at several time-points using objective measures) is involved in the pathophysiology of Alzheimer's disease.
Published: 2015

24. Fatty Acid Profiles in Demented Patients: Identification of Hexacosanoic Acid (C26:0) as a Blood Lipid Biomarker of Dementia

Author: Meryam Debbabi, Samia Hadj Ahmed, Wafa Chaabane, Sofiene Ben Ammou, Mahbouba Frih, Amira Zarrouk, Olivier Rouaud, Jean-Marc Riedinger, Gérard Lizard, Mohamed Hammami, and Sonia Hammami
Subjects: Male, medicine.medical_specialty, Pathology, Chromatography, Gas, Erythrocytes, Blood lipids, Neuropsychological Tests, Biology, Mass Spectrometry, chemistry.chemical_compound, Internal medicine, medicine, Humans, Dementia, Vascular dementia, Aged, Aged, 80 and over, chemistry.chemical_classification, Fatty acid metabolism, General Neuroscience, Fatty Acids, Fatty acid, Lipid metabolism, General Medicine, Middle Aged, Peroxisome, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Endocrinology, ROC Curve, chemistry, Biomarker (medicine), Female, Geriatrics and Gerontology, Mental Status Schedule
Abstract: Background: Several lipid metabolism alterations have been described in the brain and plasma of Alzheimer’s disease (AD) patients, suggesting a relation between lipid metabolism alteration and dementia. 15 16 Objective: We attempted to identify blood fatty acids as biomarkers of dementia. 17 Methods: Fatty acid profiles were established using gas chromatography with or without mass spectrometry on matched plasma and red blood cells (RBCs) of demented patients diagnosed with AD, vascular dementia, or other dementia, and compared with a control group of elderly individuals. The severity of dementia was evaluated with the Mini-Mental State Examination test. 18 19 20 Results: Fatty acid analysis showed significant variations of fatty acid levels in demented patients including AD patients. The highest plasma and RBC accumulation was found with hexacosanoic acid (C26:0). These data suggest that alterations of desaturase and elongase activity may contribute to cognitive dysfunction. 21 22 23 Conclusion: The variations of fatty acid levels and the accumulation of C26:0 in the plasma and RBCs highlight an alteration of fatty acid metabolism in demented patients and point toward possible peroxisomal dysfunction. It is suggested that C26:0 may constitute a convenient blood biomarker of dementia that could be useful in routine medical practice. 24 25 26
Published: 2015

25. Carotid plaque as a predictor of dementia in older adults: The Three‐City Study

Author: Olivier Rouaud, Bilal Majed, Christophe Tzourio, Mahmoud Zureik, Jean-François Dartigues, Karen Ritchie, Matthieu Plichart, Jean-Philippe Empana, and Laure Carcaillon
Subjects: Carotid Artery Diseases, Male, Risk, medicine.medical_specialty, Epidemiology, Disease, Competing risks, Carotid Intima-Media Thickness, Sensitivity and Specificity, Cellular and Molecular Neuroscience, Developmental Neuroscience, Risk Factors, Internal medicine, Humans, Medicine, Dementia, Prospective Studies, cardiovascular diseases, Stroke, Aged, Aged, 80 and over, business.industry, Incidence, Health Policy, Carotid ultrasonography, Prognosis, medicine.disease, Plaque, Atherosclerotic, Confidence interval, Surgery, Psychiatry and Mental health, Carotid Arteries, Intima-media thickness, cardiovascular system, Cardiology, Female, Neurology (clinical), Geriatrics and Gerontology, business, Follow-Up Studies
Abstract: Background The contribution of carotid atherosclerosis to incident dementia remains unclear. We examined the association between carotid plaques (CP) and common carotid intima media thickness (CCA-IMT) with incident dementia and its subtypes, and their added value for dementia risk prediction. Methods At baseline, 6025 dementia-free subjects aged 65–86 years underwent bilateral carotid ultrasonography measures of CP and plaque-free CCA-IMT. Subjects were followed-up over 7 years for the detection of dementia. Results After a mean 5.4 years of follow-up, 421 subjects developed dementia including 272 Alzheimer's disease and 83 vascular/mixed dementia (VaD). Only CP were independently related to VaD (HR ≥2 sites with plaques = 1.92; 95% confidence interval or CI = 1.13–3.22) and improved VaD risk prediction (continuous Net Reclassification Index = 30.1%; 95%CI = 8.4–51.7) beyond known dementia risk factors. Accounting for stroke or competing risk by death marginally modified the results. Conclusion In older adults, CP are independent predictors of incident VaD and may improve VaD risk prediction.
Published: 2014

26. [O1–13–05]: IS THE PROSPECTIVE ASSOCIATION BETWEEN DOMAIN‐SPECIFIC COGNITIVE IMPAIRMENT AND INCIDENT DEMENTIA MODIFIED BY EDUCATION? THE MEMENTO COHORT

Author: Frédéric Blanc, Jacques Hugon, Bruno Dubois, Serge Belliard, Mathieu Ceccaldi, Sophie Auriacombe, Olivier Hanon, Olivier Rouaud, Geneviève Chêne, Pierre Jean Ousset, Catherine Thomas-Antérion, Renaud David, Florence Pasquier, Alexandra Foubert-Samier, Carole Dufouil, Pierre Krolak Salmon, and Audrey Gabelle
Subjects: Epidemiology, business.industry, Health Policy, medicine.disease, Domain (software engineering), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, Medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment, Association (psychology), Clinical psychology
Published: 2017

27. [O2–10–05]: SHORT‐TERM PREDICTION OF CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO DEMENTIA IN PATIENTS IN THE MEMENTO COHORT, 2011–2016

Author: Renaud David, Jean-François Mangin, Emilie Beaufils, Clélia Favary, Florence Pasquier, Jacques Hugon, Vincent Bouteloup, Bruno Vellas, Frédéric Blanc, Marie Chupin, Bruno Dubois, Carole Dufouil, Olivier Hanon, Pierre Krolak Salmon, Olivier Rouaud, Mathieu Ceccaldi, Geneviève Chêne, Audrey Gabelle, and François Tison
Subjects: Pediatrics, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Term (time), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, medicine, Dementia, In patient, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment
Published: 2017

28. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial

Author: Sandrine Andrieu, Sophie Guyonnet, Nicola Coley, Christelle Cantet, Marc Bonnefoy, Serge Bordes, Lawrence Bories, Marie-Noëlle Cufi, Thierry Dantoine, Jean-François Dartigues, Françoise Desclaux, Audrey Gabelle, Yannick Gasnier, Alain Pesce, Kristel Sudres, Jacques Touchon, Philippe Robert, Olivier Rouaud, Philippe Legrand, Pierre Payoux, Jean-Paul Caubere, Michael Weiner, Isabelle Carrié, Pierre-Jean Ousset, Bruno Vellas, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie Noëlle-Cuffi, Corinne Costes, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li, Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Colette Blatge, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Nicolas Lebrun, Nadège Barro-Belaygues, Karim Bennys, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule, Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital de Tarbes, Service de Gériatrie (CHARLES FOIX - Gériatrie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hopital de castres, CHU Limoges, CHU Bordeaux [Bordeaux], Hopital Lavaur, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Princesse Grace [Monaco], Centre hospitalier de Montauban, Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cognition Behaviour Technology (CobTek), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut Claude Pompidou [Nice] (ICP - Nice)-Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Recherche Agronomique (INRA), Department of Nuclear Medicine, CHU de Toulouse (CHU), Centre de Recherche Pierre Fabre, University of California [San Francisco] (UCSF), University of California, Service d'Etudes du Comportement des Matériaux de Conditionnement (SECM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, École de sages-femmes Baudelocque (ESF Baudelocque), Université Paris Descartes - Paris 5 (UPD5), Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Service de médecine gériatrique (CHU de Dijon - Centre gériatrique de Champmaillot - EHPAD), Cabinet médical [Dijon], Cabinet médical, Handicap, Activité, Vieillissement, Autonomie, Environnement (HAVAE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Sciences et Société, Historicité, Éducation et Pratiques (EA S2HEP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Mémoire de Ressources et de Recherches [Limoges] (CMRR Limoges), CHU Limoges-CH Esquirol [Limoges] (CH Esquirol), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Centre d'EPistémologie et d'ERgologie Comparatives - UMR 7304 (CEPERC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de droit privé fondamental (CDPF), Université de Strasbourg (UNISTRA)-L'europe en mutation : histoire, droit, économie et identités culturelles, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Service de Neurologie, Université Montpellier 1 (UM1)-Hôpital Guy de Chauliac-Centre Mémoire Ressources Recherche Languedoc - Roussillon, Laboratoire d'Informatique Médicale (LIM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), The Smithsonian Museum Conservation Institute, Chercheur indépendant, Centre Léon Bérard [Lyon], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Urgence et post-urgence psychiatrique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pasteur [Nice] (CHU), 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), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse]-Hôpital Rangueil, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), 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 Paris-Saclay-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Service de l'Information Médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-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 Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre hospitalier de Montauban (CH Montauban), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), Service de Médecine Nucléaire - Rangueil [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Tours (UT), Université Paris Descartes - École de sages-femmes Baudelocque (UPD ESF Baudelocque), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'EPistémologie et d'ERgologie Comparatives (CEPERC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-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), Université Montpellier 1 (UM1)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Mémoire Ressources Recherche Languedoc - Roussillon, Université de Rennes (UR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Hôpital Gui de Chauliac [CHU Montpellier], Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), 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)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Département d'Information Médicale [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), 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), French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute [Basel], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Gérontopôle, Department of Geriatrics, Centre Hospitalier Universitaire de Toulouse, Geriatrics Department, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), hopital de Foix, U897, Memory Research Resource Center for Alzheimer's Disease, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Princesse Grace, Hopital Montauban, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), Memory Research Resource Center, Neurology Department, Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, Department of Nuclear Medicine, National Institute of Neurosurgery, Toulouse NeuroImaging Centre, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], 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), UMR E4320 (TIRO-MATOs), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, [SDV]Life Sciences [q-bio], Placebo-controlled study, Neuropsychological Tests, decline, law.invention, 0302 clinical medicine, Cognition, Randomized controlled trial, prevention, law, Medicine, 030212 general & internal medicine, Cognitive decline, alzheimers-disease, risk, chemistry.chemical_classification, Aged, 80 and over, education.field_of_study, Eicosapentaenoic acid, 3. Good health, Exercise Therapy, Treatment Outcome, Female, performance, Polyunsaturated fatty acid, medicine.medical_specialty, brain, Population, Placebo, 03 medical and health sciences, Double-Blind Method, Fatty Acids, Omega-3, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, plasma, Aged, clinical-trials, Memory Disorders, Cognitive Behavioral Therapy, business.industry, Clinical trial, chemistry, Dietary Supplements, Physical therapy, Neurology (clinical), business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, gait speed, 030217 neurology & neurosurgery, dementia
Abstract: Summary Background No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. Methods The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). Findings 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (−0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (−0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. Interpretation The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. Funding French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.
Published: 2017

29. 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

30. Dual effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-Induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells

Author: Jean-Marc Riedinger, Thomas Nury, Amira Zarrouk, Gérard Lizard, Mohamed Hammami, and Olivier Rouaud
Subjects: medicine.medical_specialty, Docosahexaenoic Acids, Medicine (miscellaneous), Mitochondrion, medicine.disease_cause, Cell Line, Lipid peroxidation, chemistry.chemical_compound, Alzheimer Disease, Internal medicine, medicine, Humans, Cytotoxic T cell, Cell Proliferation, Neurons, chemistry.chemical_classification, Reactive oxygen species, Nutrition and Dietetics, business.industry, Cell growth, Fatty Acids, Glutathione, Mitochondria, Oxidative Stress, Endocrinology, chemistry, Docosahexaenoic acid, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, Geriatrics and Gerontology, Reactive Oxygen Species, business, Oxidative stress
Abstract: Increased levels of C22:0, C24:0 and C26:0 were found in cortical lesions of patients with Alzheimer's disease (AD). So, it was of interest to precise the cytotoxic effects of these fatty acids, and to determine whether docosahexaenoic acid (DHA), described to prevent AD, can attenuate their eventual side effects. Human neuronal SK-N-BE cells were cultured in the absence or presence of C22:0, C24:0 or C26:0 (0.1-20 µM) without or with DHA (50-150 µM). C22:0, C24:0 and C26:0 induce an inhibition of cell growth, a loss of Δψm, an overproduction of reactive oxygen species (ROS), a decrease of reduced glutathione, and a lipid peroxidation. DHA attenuates C22:0, C24:0 and C26:0 induced-mitochondrial dysfunctions and/or cell growth inhibition measured with MTT whatever the concentrations considered, whereas it can either decrease or amplify (especially at 150 µM) ROS overproduction. C22:0, C24:0 and C26:0 have neurotoxic activities, and depending on its concentration, DHA attenuates or not fatty acid-induced side effects.
Published: 2014

31. Post-Stroke Cognitive Impairment: High Prevalence and Determining Factors in a Cohort of Mild Stroke

Author: Anny Graule-Petot, Christine Binquet, Benoit Daubail, Claire Bonithon-Kopp, Maurice Giroud, Yannick Béjot, Guy-Victor Osseby, Olivier Rouaud, and Agnès Jacquin
Subjects: Male, medicine.medical_specialty, Observation, Neuropsychological Tests, Cohort Studies, Diabetes mellitus, Aphasia, Internal medicine, Prevalence, Humans, Medicine, Dementia, Prospective cohort study, Stroke, Aged, Aged, 80 and over, business.industry, General Neuroscience, Age Factors, Montreal Cognitive Assessment, Cognition, General Medicine, Middle Aged, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Cohort, Female, Geriatrics and Gerontology, medicine.symptom, Cognition Disorders, Mental Status Schedule, business
Abstract: BACKGROUND Because of the aging population and a rise in the number of stroke survivors, the prevalence of post-stroke cognitive impairment (PSCI) is increasing. OBJECTIVE To identify the factors associated with 3-month PSCI. METHODS All consecutive stroke patients without pre-stroke dementia, mild cognitive disorders, or severe aphasia hospitalized in the Neurology Department of Dijon, University Hospital, France (November 2010 - February 2012) were included in this prospective cohort study. Demographics, vascular risk factors, and stroke data were collected. A first cognitive evaluation was performed during the hospitalization using the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MOCA). Patients assessable at 3 months were categorized as cognitively impaired if the MMSE score was ≤26/30 and MOCA
Published: 2014

32. Impact of a premature menopause on cognitive function in later life

Author: Karen Ritchie, Hélène Amieva, Joanne Ryan, Isabelle Carrière, Jacqueline Scali, M-L Ancelin, Olivier Rouaud, and Claudine Berr
Subjects: Gerontology, Pediatrics, medicine.medical_specialty, Ovariectomy, Menopause, Premature, Transdermal Patch, Neuropsychological Tests, Primary Ovarian Insufficiency, Surgical Menopause, Cognition, Visual memory, Risk Factors, Humans, Medicine, Verbal fluency test, Premature Menopause, Aged, Aged, 80 and over, Psychomotor learning, Estradiol, business.industry, Estrogen Replacement Therapy, Obstetrics and Gynecology, Estrogens, medicine.disease, Premature ovarian failure, Menopause, Logistic Models, Multivariate Analysis, Dementia, Female, business, Psychomotor Performance
Abstract: To determine whether premature menopause (≤40 years) can have long-lasting effects on later-life cognition and investigate whether this association varies depending on the type of menopause and use of hormone treatment (HT).Population-based cohort study.The French Three-City Study.Four thousand eight hundred and sixty-eight women aged at least 65 years.Multivariable-adjusted logistic regression models were used to determine the association between age at menopause, type of menopause (surgical, natural), and the use of menopausal HT and later-life cognitive function.Performance on a cognitive test battery (at baseline and over 7 years) and clinical dementia diagnosis.Menopause at or before the age of 40 years, both premature bilateral ovariectomy and premature ovarian failure (non-surgical loss of ovarian function), was associated with worse verbal fluency (OR 1.56, 95%CI 1.12-1.87, P=0.004) and visual memory (OR 1.39, 95%CI 1.09-1.77, P=0.007) in later life. HT at the time of premature menopause appeared beneficial for later-life visual memory but increased the risk of poor verbal fluency. Type of menopause was not significantly associated with cognitive function. Premature menopause was associated with a 30% increased risk of decline in psychomotor speed and global cognitive function over 7 years.Both premature surgical menopause and premature ovarian failure were associated with long-term negative effects on cognitive function, which are not entirely offset by menopausal HT. In terms of surgical menopause, these results suggest that the potential long-term effects on cognitive function should form part of the risk/benefit ratio when considering ovariectomy in younger women.
Published: 2014

33. The Impact of World and European Football Cups on Stroke in the Population of Dijon, France: A Longitudinal Study from 1986 to 2006

Author: Catherine Quantin, Guy-Victor Osseby, Marie Hervieu-Bègue, Agnès Jacquin, Yannick Béjot, Jérôme Durier, Jonathan Cottenet, Olivier Rouaud, Corine Aboa-Eboulé, Maurice Giroud, and Mehni Khellaf
Subjects: Male, Competitive Behavior, Longitudinal study, Time Factors, Population, Football, Risk Assessment, symbols.namesake, Risk Factors, Soccer, Odds Ratio, Humans, Medicine, Longitudinal Studies, Registries, Poisson regression, Championship, education, Stroke, Aged, Retrospective Studies, education.field_of_study, Chi-Square Distribution, business.industry, Rehabilitation, Euphoria, Middle Aged, medicine.disease, Confidence interval, Relative risk, Multivariate Analysis, symbols, Female, Television, Surgery, France, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Stress, Psychological, Demography
Abstract: Background: Acute stress may trigger vascular events. We aimed to investigate whether important football competitions involving the French football team increased the occurrence of stroke. Methods: We retrospectively retrieved data of fatal and nonfatal stroke during 4 World Football Cups (1986, 1998, 2002, and 2006) and 4 European Championships (1992, 1996, 2000, and 2004), based on data from the population-based Stroke Registry of Dijon, France. One period of exposure was analyzed: the period of competition extended to 15 days before and after the competitions. The number of strokes was compared between exposed and unexposed corresponding periods of preceding and following years using Poisson regression. Results: A total of 175 strokes were observed during the exposed periods compared with 192 and 217 strokes in the unexposed preceding and following periods. Multivariate regression analyses showed an overall 30% significant decrease in stroke numbers between periods of competition and unexposed periods of following year (risk ratio (RR) 5 1.3; 95% confidence interval [CI] 5 1.0-1.6; P 5.029) but not with that of preceding year (RR 5 1.1; 95% CI 5 .9-1.3; P 5.367). This was mostly explained by a 40% decrease in stroke numbers during European Championships, compared with the unexposed following periods (RR 5 1.4; 95% CI 5 1.0-1.9; P 5.044) in stratified analyses by football competitions. Conclusions: Watching European football competitions had a positive impact in the city of Dijon with a decrease of stroke numbers. European championship is possibly associated with higher television audience and long-lasting euphoria although other factors may be involved. Further studies using nationwide data are recommended to vali
Published: 2014

34. Assessment of French bread texture by a multi-indentation test

Author: A. Rzigue, Aamir Shehzad, Hubert Chiron, G. Della Valle, Laurent Chaunier, Olivier Rouaud, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), National Institute of Food Science & Technology, and University of Agriculture Faisalabad - UAF (PAKISTAN)
Subjects: Materials science, 030309 nutrition & dietetics, Mixing (process engineering), Density, Mineralogy, Mechanical properties, Materials testing, Force sensor, 03 medical and health sciences, 0404 agricultural biotechnology, Indentation, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Texture (crystalline), Composite material, 0303 health sciences, Compression, Stiffness, Fibres, 04 agricultural and veterinary sciences, Compression (physics), Crust, 040401 food science, Constant rate, medicine.symptom, Baking, Food Science
Abstract: A specific equipment, made of an assembly of 10-20 vertical metal pins, has been implemented to assess the crusty texture of French breads by a so called multi-indentation test. It was connected to a force sensor set on a material testing machine in the range [0; 100 N]. The height of each pin was adjustable to the irregular surface of the crust of the tested specimen. Breads with varying texture were prepared under various dough mixing conditions and formats, different baking times (8, 11, 15 and 17 min), and with various contents of bioprocessed fibres. They were crushed, by the multi-indenter at a constant rate (50 mm/min), followed by a relaxation step while maintaining stable the final strain at 2/3rd of the initial sample height. Main variables measured from the resulting texture profile were related to crust stiffness and crumb firmness. The relevant bread format, accurate baking time and fibres content could be selected in function of given crust properties. Overall, the multi-indentation test proved a useful procedure to contribute to the design of breads with target texture. (C) 2013 Elsevier Ltd. All rights reserved.
Published: 2014

35. High plasma estradiol interacts with diabetes on risk of dementia in older postmenopausal women

Author: Anne Guiochon-Mantel, Jean-François Dartigues, Marie-Laure Ancelin, Sylvie Brailly-Tabard, Olivier Rouaud, Pierre-Yves Scarabin, and Laure Carcaillon
Subjects: Risk, medicine.medical_specialty, Population, Cohort Studies, Fibrin Fibrinogen Degradation Products, Risk Factors, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Thrombophilia, Dementia, Testosterone, Prospective cohort study, education, Aged, Proportional Hazards Models, Aged, 80 and over, Inflammation, education.field_of_study, Estradiol, biology, Proportional hazards model, business.industry, Hazard ratio, C-reactive protein, Thrombin, Case-control study, Fibrinogen, medicine.disease, Postmenopause, C-Reactive Protein, Case-Control Studies, Multivariate Analysis, biology.protein, Female, France, Neurology (clinical), business, Biomarkers
Abstract: We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association.Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases.Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1-4.5] and HR = 2.4 [1.2-5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60-123] and HR = 3.4 [0.1-147], respectively, p interaction0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone.High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.
Published: 2014

36. MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER’S DISEASE: DESIGN AND BASELINE DATA

Author: Stéphane Lehéricy, Sophie Gillette-Guyonnet, Charlotte Dupuy, P Cestac, Alain Pesce, Françoise Lala, Sherry L. Willis, Sandrine Andrieu, Laurent Molinier, Christelle Cantet, Serge Bordes, G. Abellan Van Kan, Marie Chupin, D. Adel, Maria Soto, Olivier Rouaud, Sylvie Belleville, Fati Nourhashemi, Yves Rolland, Catherine Faisant, M.-N. Cuffi, Matteo Cesari, Philippe Legrand, Thierry Voisin, Jacques Touchon, Isabelle Carrié, J. Delrieu, Lawrence Bories, Carole Dufouil, M. Zaim, Bruno Vellas, Pierre Payoux, Kristelle Sudres, Jean-François Mangin, Pierre-Jean Ousset, Françoise Desclaux, Marc Bonnefoy, D Catheline, J. F. Dartigues, Thierry Dantoine, P. Robert, M. Weiner, Nadège Costa, C Kanony, and Yannick Gasnier
Subjects: Gerontology, medicine.medical_specialty, Cognitive stimulation, business.industry, Psychological intervention, Cognition, Physical exercise, Disease, Baseline data, Nutritional counseling, Physical medicine and rehabilitation, Neuroimaging, medicine, business
Abstract: Objective: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). Design, patients: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). Interventions: 1/ Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6–8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. Baseline population: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. Discussion: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.
Published: 2014

37. Trends in the incidence of ischaemic stroke in young adults between 1985 and 2011: the Dijon Stroke Registry

Author: Yannick Béjot, Olivier Rouaud, Agnès Jacquin, Maurice Giroud, Benoit Daubail, Guy-Victor Osseby, and Jérôme Durier
Subjects: Male, Stroke registry, Pediatrics, medicine.medical_specialty, Population, Brain Ischemia, symbols.namesake, Risk Factors, Ischaemic stroke, Epidemiology, medicine, Humans, Registries, Poisson regression, Young adult, education, Stroke, Aged, Cerebral Hemorrhage, Aged, 80 and over, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), Age Factors, Middle Aged, medicine.disease, Psychiatry and Mental health, symbols, Female, Surgery, France, Neurology (clinical), business
Abstract: Recent data have suggested that stroke incidence in young people may be rising. In this population-based study, we aimed to determine whether the incidence of stroke in people aged55 years old had changed over the last three decades.All cases of first-ever stroke (ischaemic stroke, spontaneous intracerebral haemorrhage, and undetermined stroke) occurring in Dijon, France, from 1985 to 2011 were prospectively collected from a population-based registry. Incidence rates were calculated and temporal trends were analysed by age groups and stroke subtypes using a Poisson regression to estimate incidence rate ratios (IRR). Risk factors and premorbid treatments were analysed.Over the 27-year study period, 4506 patients were recorded (53% women, mean age 74.6±14.4, 10.1% aged55 years). An increase in overall stroke incidence was noted, as was a rise in ischaemic stroke in individuals aged55 years (IRR 1.308; 95% CI 0.982 to 1.741, p=0.066 for period 1994-2002 vs period 1985-1993, and IRR 1.697; 95% CI 1.340 to 2.150, p0.001 for period 2003-2011 vs period 1994-2002), which was consistent for men and women. In these young patients, smoking was the most frequent risk factor (43%).Multiple factors may account for the increased incidence of ischaemic stroke in people aged55 years including changes in vascular risk factors, better awareness of the disease and treatment options in the population and among practitioners leading to more frequent referrals for specialised care, and improvements in stroke diagnosis. Stroke prevention must be encouraged even in young adults.
Published: 2013

38. Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H) in a French Family

Author: Marie Sarazin, Maurice Giroud, Inna Dygai-Cochet, Yannick Béjot, Pierre Soichot, Tania Stojkovic, Olivier Rouaud, Agnès Jacquin, Thibault Moreau, and Martine Lemesle-Martin
Subjects: medicine.medical_specialty, Weakness, business.industry, Disease, Irritability, medicine.disease, lcsh:RC346-429, Aphasia, medicine, Anxiety, Neurology (clinical), Published online: October, 2013, medicine.symptom, VCP mutation, Psychiatry, business, Inclusion body myopathy, Psychiatric disorders, lcsh:Neurology. Diseases of the nervous system, Depression (differential diagnoses), Frontotemporal dementia, Executive dysfunction
Abstract: Introduction: Inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD) is a rare late-onset autosomal dominant disorder due to a mutation of the valosin-containing protein (VCP) gene. Case Report: We report the case of a patient who developed progressive weakness of the limbs in his fifties, until he was confined to a wheelchair. At that time, he developed acute behavioural changes including irritability, severe anxiety and major depression, which led to him being hospitalised in a psychiatric hospital. He also suffered from aphasia and executive function impairment, which helped us to diagnose a behavioural form of frontotemporal dementia (FTD). The diagnosis of IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the VCP gene (R155H mutation). Discussion: The clinical diagnosis of IBMPFD is suggested by the presence of at least one of three major manifestations as follows: inclusion body myopathy (mean onset at 42 years of age), Paget's disease of the bone and FTD (mean onset at 55 years of age). It is mostly the behavioural form of FTD (behavioural changes, executive dysfunction and aphasia). One interesting finding in our report is the predominance of the psychiatric symptoms at the beginning of the behavioural changes, which led to the diagnosis of FTD. The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in the VCP gene.
Published: 2013

39. Sex Differences in the Associations Between Lipid Levels and Incident Dementia

Author: Pascale Barberger-Gateau, Anne-Marie Dupuy, Sophie Auriacombe, Olivier Rouaud, Emmanuelle Ripoche, Isabelle Carrière, Marie-Laure Ancelin, Claudine Berr, Karen Ritchie, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, 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), Laboratoire d'explorations du système nerveux (hôpital général, CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Mémoire de Ressources et de Recherche (CMRR)-Hôpital général (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Neuroscience Division, Imperial College London-St Mary's Hospital, and Fondation pour la recherche médicale, Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon and, the Fondation de France, the Ministry of Research-Inserm Programme 'Cohorts and collection of biological material'
Subjects: Male, medicine.medical_specialty, Article, Cohort Studies, 03 medical and health sciences, Elderly, 0302 clinical medicine, Internal medicine, medicine, Humans, Dementia, Risk factor, Vascular dementia, Prospective cohort study, Triglycerides, Aged, 030304 developmental biology, Aged, 80 and over, Sex Characteristics, 0303 health sciences, business.industry, Proportional hazards model, Vascular disease, Incidence, General Neuroscience, Cholesterol, HDL, Cholesterol, LDL, General Medicine, Alzheimer's disease, Prospective cohort, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Atherosclerosis, Lipid Metabolism, medicine.disease, Lipids, Apolipoprotein, Psychiatry and Mental health, Clinical Psychology, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Dyslipidemia, Follow-Up Studies, Sex characteristics
Abstract: International audience; Cholesterol is a risk factor for developing vascular pathologies, which is in turn an important risk factor for dementia. Previous studies linking lipids and dementia have yielded inconsistent results, which may be attributable to sex differences in the etiology of both vascular disease and dementia. The aim of this study was to evaluate the associations between lipids and incident dementia in 7053 community-dwelling elderly. Dementia was diagnosed at baseline, and 2, 4, and 7-year follow-up. Multivariate Cox models stratified by sex and history of vascular pathologies at baseline were adjusted for sociodemographic, mental and physical health variables, and genetic vulnerability. In men without vascular pathologies, an increased incidence of all-cause dementia but not Alzheimer's disease (AD) was associated with high triglyceride (TG) (HR = 1.55, 95% CI = 1.04-2.32, p = 0.03) and low HDL-cholesterol levels (HR = 1.49, 95% CI = 0.99-2.23, p = 0.05). In women without vascular pathologies, low TG levels were associated with a decreased risk of AD (HR = 0.65, 95% CI = 0.43-0.97, p = 0.03). A decreased risk was also found with high TG levels which may depend on genetic vulnerability to dyslipidemia related to APOA5. For both sexes, no significant associations were found between total- or LDL-cholesterol and dementia or AD. Low HDL-cholesterol and high TG levels may be risk factors of dementia in elderly men whereas low TG is associated with decreased incident AD in women. This data suggests a complex sex-specific etiology of vascular dementia and AD.
Published: 2013

40. Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study

Author: Maurice Giroud, Corine Aboa-Eboulé, Olivier Rouaud, Yannick Béjot, Charlotte Cordonnier, and Jérôme Durier
Subjects: Male, Pediatrics, medicine.medical_specialty, Population, Risk Factors, Antithrombotic, medicine, Humans, Registries, education, Stroke, Aged, Cerebral Hemorrhage, Aged, 80 and over, education.field_of_study, business.industry, Incidence (epidemiology), Middle Aged, Bleed, medicine.disease, Confidence interval, Blood pressure, Population Surveillance, Female, France, Neurology (clinical), Cerebral amyloid angiopathy, business
Abstract: Incidence of intracerebral haemorrhage over the past three decades is reported as stable. This disappointing finding is questionable and suggests that any reduction in intracerebral haemorrhage incidence associated with improvements in primary prevention, namely, better control of blood pressure, might have been offset by an increase in cases of intracerebral haemorrhage owing to other factors, including the use of antithrombotic drugs in the ageing population. Therefore, we aimed to analyse trends in intracerebral haemorrhage incidence from 1985 to 2008 in the population-based registry of Dijon, France, taking into consideration the intracerebral haemorrhage location, the effect of age and the changes in the distribution of risk factors and premorbid treatments. Incidence rates were calculated and temporal trends were analysed by age groups (
Published: 2013

41. Prestroke antiplatelet therapy and early prognosis in stroke patients: the Dijon Stroke Registry

Author: M. Hervieu, Yannick Béjot, Olivier Rouaud, Guy-Victor Osseby, M. Giroud, Agnès Jacquin, E. de Maistre, O. Troisgros, and Corine Aboa-Eboulé
Subjects: Male, medicine.medical_specialty, Stroke registry, Multivariate analysis, Population, Kaplan-Meier Estimate, Lower risk, Risk Factors, Internal medicine, medicine, Humans, Registries, education, Stroke, Aged, Aged, 80 and over, education.field_of_study, business.industry, Hazard ratio, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Early Diagnosis, Treatment Outcome, Neurology, Female, France, Neurology (clinical), business, Platelet Aggregation Inhibitors
Abstract: Background and purpose Previous antiplatelet therapy (APT) in cardiovascular prevention is common in patients with first-ever stroke. We aimed to evaluate the prognostic value of APT on early outcome in stroke patients. Methods All first-ever strokes from 1985 to 2011 were identified from the population-based Stroke Registry of Dijon, France. Demographic features, risk factors, prestroke treatments and clinical information were recorded. Multivariate analyses were performed to evaluate the associations between pre-admission APT and both severe handicap at discharge, and mortality at 1 month and 1 year. Results Among the 4275 patients, 870 (20.4%) were previously treated with APT. Severe handicap at discharge was noted in 233 (26.8%) APT users and in 974 (28.7%) non-users. Prestroke APT use was associated with lower odds of severe handicap at discharge [adjusted odds ratio (OR): 0.79; 95% confidence interval (CI): 063–1.00; P = 0.046], non-significant better survival at 1 month [adjusted hazard ratio (HR): 0.87; 95% CI: 0.70–1.09; P = 0.222] and no effect on 1-year mortality (HR: 0.94; 95% CI 0.80–1.10; P = 0.429). In stratum-specific analyses, APT was associated with a lower risk of 1-month mortality in patients with cardioembolic ischaemic stroke (HR: 0.65; 95% CI: 0.43–0.98; P = 0.040). Conclusions APT before stroke was associated with less severe handicap at discharge, with no significant protective effect for mortality at 1 month except in patients with cardioembolic stroke. No protective effect of APT was observed for mortality at 1 year. Further studies are needed to understand the mechanisms underlying the distinct effects of prior APT observed across the ischaemic stroke subtypes.
Published: 2012

42. Diagnostic Procedures in Ischaemic Stroke Patients with Dementia. A Population-Based Study

Author: Maurice Giroud, M. Hervieu, Guy-Victor Osseby, Odile Troisgros, Corine Aboa-Eboulé, Yannick Béjot, Agnès Jacquin, and Olivier Rouaud
Subjects: Aged, 80 and over, Male, medicine.medical_specialty, business.industry, Middle Aged, Stroke care, medicine.disease, Stroke, Population based study, Neurology, Emergency medicine, Epidemiology, Ischaemic stroke, Physical therapy, Humans, Medicine, Dementia, Female, business, Aged
Abstract: Background Dementia is a frequent condition in stroke patients. Aims To investigate the effect of dementia on access to diagnostic procedures in ischaemic stroke patients. Methods All cases of ischaemic stroke from 2006 to 2010 were identified from the population-based Stroke Registry of Dijon, France. Patients' characteristics were recorded, as was the use of brain computed tomography scans, brain magnetic resonance imaging, electrocardiogram, echocardiography, and Doppler ultrasonography of the cervical arteries. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Logistic regression models were used to evaluate the associations between dementia and the use of the diagnostic procedures. Results Of the 907 patients recorded, 104 were excluded because of death and inability to test cognition. Among the remaining 803 patients, 149 (18·5%) had dementia. Almost all of the patients underwent a brain computed tomography scan and an electrocardiogram during their stay. In contrast, the use of both Doppler ultrasonography of the cervical arteries (79·2% versus 90·2%, P < 0·001), echocardiography (32·9% versus 43·6%, P = 0·02), and brain magnetic resonance imaging (21·5% versus 34·4%, P < 0·001) were significantly lower in stroke patients with dementia than in those without. In multivariate logistic regression, dementia was associated with a lower use of both Doppler ultrasonography (odds ratio = 0·49; 95% confidence interval: 0·29–0·81, P = 0·005), echocardiography (odds ratio = 0·57; 95% confidence interval: 0·37–0·89, P = 0·012), brain magnetic resonance imaging (odds ratio = 0·55; 95% confidence interval: 0·34–0·89, P = 0·015), and a comprehensive assessment (odds ratio = 0·62; 95% confidence interval: 0·40–0·96, P = 0·033). Conclusion Demented patients were less likely to undergo diagnostic procedures after ischaemic stroke. Further studies are needed to determine whether this lower utilization could account for the reported excess in recurrent events in these patients.
Published: 2012

43. The Early Indicators of Functional Decrease in Mild Cognitive Impairment

Author: Olivier Rouaud, Alexandre Kubicki, Lilian Fautrelle, Julien Bourrelier, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), UFR Sciences du Sport (STAPS) (Université de Bourgogne), Université de Bourgogne ( UB ), Institut de Formation aux Métiers de la Santé [Belfort et Montbéliard] ( IFMS ), Hôpital Nord Franche-Comté [Hôpital de Trévenans] ( HNFC ), Université Paris Nanterre - UFR Sciences et Techniques des Activités Physiques et Sportives ( UPN STAPS ), Université Paris Nanterre ( UPN ), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Centre Mémoire de Ressources et de Recherche [Nice] ( CMRR Nice ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -CHU Nice, UFR des Sciences de Santé (Université de Bourgogne), ANR MAAMI project (Maladie d'Alzheimer et Apprentissage Moteur Implicite), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB), Institut de Formation aux Métiers de la Santé [Belfort et Montbéliard] (IFMS), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Université Paris Nanterre - UFR Sciences et techniques des activités physiques et sportives (UPN STAPS), Université Paris Nanterre (UPN), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Aging, medicine.medical_specialty, cognitive functions, Mild Cognitive Impairments, Cognitive Neuroscience, Population, Motor program, [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, low-back-pain, arm movements, behavioral disciplines and activities, equilibrium, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, part-b, mental disorders, medicine, motor control, voluntary, older-adults, Young adult, alzheimers-disease, education, Muscle synergy, anticipatory postural adjustments, Original Research, education.field_of_study, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, muscle synergy, age-related-changes, Motor control, Cognition, Executive functions, Low back pain, nervous system diseases, 030104 developmental biology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Physical therapy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], parkinsons-disease, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Neuroscience
Abstract: OBJECTIVES: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity of the muscle synergy involved in an arm-pointing movement in MCI patients, non-impaired functionally. Thus, we were able to test the hypothesis that early motor indicators exist in this population at a preclinical level. METHODS: The electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Aged Adults (AA), and MCI patients. The AA and MCI groups presented the same functional status. Each subject performed twenty arm-pointing movements from a standing position. RESULTS: The main differences were (1) delayed activation of the right Biceps Femoris and the right Erector Spinae at L3 in MCI patients and AA compared with YA groups ; (2) earlier activation of the left Obliquus internus in MCI compared with AA group and (3) concerning the left Erector spinae at L3, a delay for the AA compared with YA but an earlier activation for the MCI compared with both AA and YA. These temporal differences in muscle synergies were linked with executive functions of MCI patients. INTERPRETATION: The motor program changes highlighted in our patient (MCI) group suggest that discrete modifications of the motor command seem to exist even in the absence of functional impairment. Instead of showing an indication of delayed muscle activation in the MCI patients, our results highlight some early activation of several trunk muscles, probably used in a more cautious motor behavior.
Published: 2016

44. O1‐08‐05: Apoe Gene Modifies the Link Between Type 2 Diabetes and Dementia Risk: the Memento Cohort

Author: Pierre Jean Ousset, Pierre Krolak Salmon, Frédéric Blanc, Mathieu Ceccaldi, Olivier Rouaud, Jean-François Mangin, Geneviève Chêne, Jacques Hugon, Bruno Dubois, Carole Dufouil, Sophie Auriacombe, Renaud David, Olivier Hanon, Florence Pasquier, Marie Chupin, and Audrey Gabelle
Subjects: Oncology, Apolipoprotein E, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Type 2 diabetes, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cohort, Medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2016

45. P2‐078: Are Alzheimer’s Disease Risk Genes Related to Markers of Brain Pathology? The Memento Cohort

Author: Bruno Dubois, Olivier Rouaud, Bruno Vellas, Jean-François Mangin, Geneviève Chêne, Philippe Amouyel, Florence Pasquier, Marie Chupin, Audrey Gabelle, Frédéric Blanc, Renaud David, Mathieu Ceccaldi, Jacques Hugon, Grégory Operto, Carole Dufouil, Jean-François Dartigues, Olivier Hanon, and Pierre Krolak Salmon
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cohort, medicine, Disease risk, Neurology (clinical), Geriatrics and Gerontology, business, Gene
Published: 2016

46. P1‐394: Prevalence and Characteristics of Patients with Alzheimer’s Disease Eligible for a Disease Modifying Drug (Panacea)

Author: Bruno Dubois, Florence Pasquier, Martine Vercelletto, Athanase Benetos, David Wallon, Olivier Rouaud, Philippe Robert, Pierre Krolak Salmon, Didier Hannequin, Stéphane Epelbaum, Anne-Sophie Rigaud, François Sellal, Caroline Hommet, Claire Boutoleau-Bretonnière, and Aurélie Mouton
Subjects: Drug, medicine.medical_specialty, biology, Epidemiology, business.industry, Health Policy, media_common.quotation_subject, Disease, biology.organism_classification, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Physical therapy, Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business, Panacea (butterfly), media_common
Published: 2016

47. P2‐304: Deficits in Visual Recognition Memory: A Marker of Early Mesial Temporal Lobe Degeneration in Nondemented Outpatients from Memory Clinics?

Author: Bruno Dubois, Mira Didic, Jacques Hugon, Florence Pasquier, Olivier Hanon, Mathieu Ceccaldi, Frédéric Blanc, Vincent Bouteloup, Pierre Jean Ousset, Jean-François Dartigues, Pierre Krolak Salmon, Audrey Gabelle, Renaud David, Carole Dufouil, Emmanuel J. Barbeau, Olivier Rouaud, Jean-François Mangin, and Geneviève Chêne
Subjects: Epidemiology, business.industry, Health Policy, Degeneration (medical), Temporal lobe, Visual recognition, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published: 2016

48. Telemedicine for the acute management of stroke in Burgundy, France: an evaluation of effectiveness and safety

Author: Benoit Daubail, M. Giroud, Marie Hervieu-Bègue, Yannick Béjot, Guy-Victor Osseby, Olivier Rouaud, Benoit Delpont, Anaïs Daumas, Nicolas Legris, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Registre Dijonnais des Accidents Vasculaires Cérébraux (AVC) - Dijon Stroke Registry, Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), UNICANCER-UNICANCER-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Adult, Male, medicine.medical_specialty, thrombolysis, medicine.medical_treatment, Context (language use), 030204 cardiovascular system & hematology, Logistic regression, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Modified Rankin Scale, Neoplasms, Case fatality rate, medicine, Humans, Thrombolytic Therapy, Intensive care medicine, Stroke, Aged, Aged, 80 and over, business.industry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Thrombolysis, Odds ratio, Middle Aged, medicine.disease, stroke, Confidence interval, 3. Good health, Treatment Outcome, Neurology, Tissue Plasminogen Activator, Emergency medicine, outcome, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, Patient Safety, prognosis, telemedicine, business, 030217 neurology & neurosurgery
Abstract: Background In the context of the development of telemedicine in France to address low thrombolysis rates and limited stroke infrastructures, a star-shaped telestroke network was implemented in Burgundy (1.6 million inhabitants). We evaluated the safety and effectiveness of this network for thrombolysis in acute ischemic stroke patients. Methods One hundred and thirty-two consecutive patients who received intravenous thrombolysis during a telemedicine procedure (2012–2014) and 222 consecutive patients who were treated at the stroke center of Dijon University Hospital, France (2011–2012) were included. Main outcomes were the modified Rankin scale (mRS) score and case fatality at 3 months. Comparisons between groups were made using multivariable ordinal logistic regression and logistic regression analyses, respectively. Results Baseline characteristics of telethrombolysis patients were similar to those of patients undergoing thrombolysis locally except for a higher frequency of previous cancer and pre-morbid handicap, and a trend towards greater severity at admission in the former. The distribution of mRS scores at 3 months was similar between groups, as were case-fatality rates (18.9% in the telethrombolysis group versus 16.5%, P = 0.56). In multivariable models, telethrombolysis did not independently influence functional outcomes at 3 months (odds ratio for a shift towards a worse outcome on the mRS, 1.11; 95% confidence interval, 0.74–1.66, P = 0.62) or death (odds ratio, 0.86; 95% confidence interval, 0.44–1.69, P = 0.66). Conclusion The implementation of a regional telemedicine network for the management of acute ischemic stroke appeared to be effective and safe. Thanks to this network, the proportion of patients who benefit from thrombolysis will increase. Further research is needed to evaluate economic benefits.
Published: 2016

49. Temporal trends in early case-fatality rates in patients with intracerebral hemorrhage

Author: Maurice Giroud, Charlotte Cordonnier, Michael Grelat, Marie Hervieu-Bègue, Jérôme Durier, Benoit Delpont, Guy-Victor Osseby, Olivier Rouaud, and Yannick Béjot
Subjects: Male, medicine.medical_specialty, Population, Community Health Planning, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Case fatality rate, medicine, Humans, In patient, 030212 general & internal medicine, Mortality, education, Aged, Cerebral Hemorrhage, Proportional Hazards Models, Intracerebral hemorrhage, Aged, 80 and over, education.field_of_study, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Female, Neurology (clinical), France, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objective:To assess whether temporal trends in very early (within 48 hours) case-fatality rates may differ from those occurring between 48 hours and 30 days in patients with spontaneous intracerebral hemorrhage (ICH).Methods:All cases of ICH that occurred in Dijon, France (151,000 inhabitants), were prospectively collected between 1985 and 2011, using a population-based registry. Time trends in 30-day case fatality were analyzed in 3 periods: 1985–1993, 1994–2002, and 2003–2011. Cox regression models were used to evaluate associations between time periods and case fatality within 48 hours and between 48 hours and 30 days, after adjustments for demographics, risk factors, severity, and ICH location.Results:A total of 531 ICH cases were recorded (mean age 72.9 ± 15.8, 52.7% women). Thirty-day case fatality gradually decreased with time from 40.9% in 1985–1993 to 33.5% 1994–2002 and to 29.6% in 2003–2011 (adjusted hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.47–1.07, p = 0.106, for 1994–2002, and adjusted HR 0.49, 95% CI 0.32–0.73, p < 0.001, for 2003–2011). Over the whole study period, 43.6% of 1-month deaths occurred within the first 48 hours following ICH onset. There was no temporal change in case fatality occurring within the first 48 hours but a decrease in deaths occurring between 48 hours and 30 days was observed with time (HR 0.53, 95% CI 0.31–0.90, p = 0.02, for 1994–2002, and HR 0.32, 95% CI 0.32–0.55, p < 0.01, for 2003–2011, compared with 1985–1993).Conclusion:Although 30-day case fatality significantly decreased over the last 27 years, additional improvements in acute management of ICH are needed since very early case-fatality rates (within 48 hours) did not improve.
Published: 2016

50. Psychotropic drug prescription in patients with dementia: nursing home residents versus patients living at home

Author: Olivier Rouaud, Maurice Giroud, Philippe Robert, Bruno Vellas, Agnès Jacquin-Piques, Neda Tavassoli, Guillaume Sacco, Sylvie Bonin-Guillaume, Yannick Béjot, Centre Mémoire de Ressources et de Recherches, Department of Neurology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Mémoire de Ressource et de Recherche, EA CoBTeK, Université de Nice Sophia-Antipolis (UNSA), Pôle Gériatrie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Internal Medicine and Geriatrics, Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Gérontopôle de Toulouse, Département de Médecine Interne et Gérontologie Clinique, and Centre Hospitalier Universitaire de Toulouse
Subjects: Male, Databases, Factual, medicine.medical_treatment, Psychological intervention, drogue, Hypnotic, psychotrope, 0302 clinical medicine, Residence Characteristics, old age homes, 030212 general & internal medicine, senior citizens, Aged, 80 and over, General Neuroscience, General Medicine, maison de retraite, 3. Good health, Psychiatry and Mental health, Clinical Psychology, nursing home, Psychotropic drug, antidepressants, Population study, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychosocial, psychotropic drug, posologie, medicine.medical_specialty, medicine.drug_class, national Alzheimer’s data bank, Drug Prescriptions, personne âgée, 03 medical and health sciences, antidépresseur, medicine, Dementia, Humans, Medical prescription, Antipsychotic, Psychiatry, Aged, Psychotropic Drugs, prescription, Chi-Square Distribution, démence, business.industry, medicine.disease, Nursing Homes, Cross-Sectional Studies, narcotics, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, dementia
Abstract: Background: Psychotropic drugs are frequently prescribed in nursing homes (NH). Nonetheless, we hoped that institutionalization decreases the number of psychotropic drug classes prescribed, because NH residents may have more psychosocial interventions than patients living at home. Objective: The aim was to compare the type and number of psychotropic drugs prescribed in elderly NH residents with dementia with those in community-living patients. Methods: This cross-sectional study included elderly patients (at least 75 years old) with dementia recorded in the National Alzheimer’s data Bank (“Banque Nationale Alzheimer”) during the year 2012 and who were taking at least one psychotropic drug. Psychotropic drugs were classified as follows: antidepressant, anxiolytic, hypnotic, and antipsychotic drugs. Patients were classified into three categories of dementia severity according to the MMSE score. Results: Among the 50,932 patients with dementia recorded in the BNA, 40.1% had at least one psychotropic drug prescribed. Most of the patients who were treated by at least one psychotropic drug class had antidepressant therapy (69.0%), whatever their residence type, and 16.1% were treated with antipsychotics. Among the study population, 51.9% of the NH residents and 67.4% of the patients living at home had only one psychotropic drug class prescribed. Living in a NH was significantly associated with the more frequent prescription of anxiolytic, hypnotic, and antipsychotic drugs, and with a greater number of psychotropic drug classes prescribed, whatever the severity of the dementia. Conclusion: We underlined the more frequent prescription of psychotropic drugs in NH residents regardless of MMSE scores.
Published: 2016

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