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1. Genetic variants for head size share genes and pathways with cancer

Author

Knol, Maria J, Poot, Raymond A, Evans, Tavia E, Satizabal, Claudia L, Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C, van Dam-Nolen, Dianne HK, Lamballais, Sander, Pawlak, Mikolaj A, Lewis, Cora E, Carrion-Castillo, Amaia, van Erp, Theo GM, Reinbold, Céline S, Shin, Jean, Scholz, Markus, Håberg, Asta K, Kämpe, Anders, Li, Gloria HY, Avinun, Reut, Atkins, Joshua R, Hsu, Fang-Chi, Amod, Alyssa R, Lam, Max, Tsuchida, Ami, Teunissen, Mariël WA, Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S, Beyer, Frauke, Bis, Joshua C, Bos, Daniel, Bryan, R Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte AM, Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M, Franke, Barbara, Freedman, Barry I, Friedrich, Nele, Green, Melissa J, Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M Kamran, Jack, Clifford R, Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R, Li, Shuo, Lim, Keane, Longstreth, WT, Macciardi, Fabio, Consortium, The Cohorts for Heart and Aging Research in Genomic Epidemiology, Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S, Bastin, Mark E, Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L, Deary, Ian J, Fleischman, Debra A, Gottesman, Rebecca F, Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J Wouter, Liewald, David CM, Lopez, Lorna M, Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J, Nyquist, Paul, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M, Yanek, Lisa, Yang, Jingyun, and Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis

Subjects
Biomedical and Clinical Sciences, Neurosciences, Biotechnology, Genetics, Cancer, Stem Cell Research, Human Genome, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Humans, Genome-Wide Association Study, Head, Neoplasms, Female, Male, Polymorphism, Single Nucleotide, Genetic Variation, Organ Size, Signal Transduction, Adult, Genetic Predisposition to Disease, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis, Biomedical and clinical sciences
Abstract

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Published
2024

2. Alzheimer in the City

Author

Dartigues Jean-François

Subjects
Alzheimer’s disease, epidemiology, recourse to care, secular trends, Oils, fats, and waxes, TP670-699
Abstract

Alzheimer’s disease was described in 1906, but it was only in 1987 that it was recognized as a public health problem with the actions of patient family associations. Despite successive Alzheimer plans, it remains a neglected and under-diagnosed disease. The lack of curative treatment and a clash of views between general practitioners and specialists explain these findings. Paradoxically, despite this neglect, Alzheimer’s disease is receding in the city. This is the proof that prevention is possible.

Published
2018
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3. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

5. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E, Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C, Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A, Boland, Anne, Damotte, Vincent, van der Lee, Sven J, Costa, Marcos R, Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C, Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J, Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E, Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J, Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S, Calero, Miguel, Cantwell, Laura B, Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen AHR, Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D, Debette, Stéphanie, Deckert, Jürgen, and del Ser, Teodoro

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Human Genome, Prevention, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Cognitive Dysfunction, Genome-Wide Association Study, Humans, tau Proteins, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Published
2022

6. Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome‐wide association study in over 12,000 non‐demented participants

Author

Damotte, Vincent, van der Lee, Sven J, Chouraki, Vincent, Grenier‐Boley, Benjamin, Simino, Jeannette, Adams, Hieab, Tosto, Giuseppe, White, Charles, Terzikhan, Natalie, Cruchaga, Carlos, Knol, Maria J, Li, Shuo, Schraen, Susanna, Grove, Megan L, Satizabal, Claudia, Amin, Najaf, Berr, Claudine, Younkin, Steven, Initiative, Alzheimer's Disease Neuroimaging, Gottesman, Rebecca F, Buée, Luc, Beiser, Alexa, Knopman, David S, Uitterlinden, Andre, DeCarli, Charles, Bressler, Jan, DeStefano, Anita, Dartigues, Jean‐François, Yang, Qiong, Boerwinkle, Eric, Tzourio, Christophe, Fornage, Myriam, Ikram, M Arfan, Amouyel, Philippe, de Jager, Phil, Reitz, Christiane, Mosley, Thomas H, Lambert, Jean‐Charles, Seshadri, Sudha, and van Duijn, Cornelia M

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Alzheimer's Disease, Dementia, Prevention, Genetics, Aging, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Amyloid, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor, Apolipoproteins E, Aspartic Acid Endopeptidases, Brain, Genome-Wide Association Study, Healthy Volunteers, Humans, Positron-Emission Tomography, Presenilin-2, Alzheimer&apos, s disease, APOE, APP, BACE1, endophenotype, genetic epidemiology, genome&#8209, wide association study, plasma amyloid beta levels, plasma biomarkers, preclinical biomarkers, PSEN2, Alzheimer's Disease Neuroimaging Initiative, Alzheimer's disease, genome-wide association study, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionThere is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures.MethodsWe included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk.ResultsSingle-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition.DiscussionIdentification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD.

Published
2021

7. The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

Author

Perquin Magali, Schuller Anne-Marie, Vaillant Michel, Diederich Nico, Bisdorff Alexandre, Leners Jean-Claude, D’Incau Marylène, Ludewig Jean-Luc, Hoffmann Danielle, Ulbricht Dirk, Thoma Stephanie, Dondelinger René, Heuschling Paul, Couffignal Sophie, Dartigues Jean-François, and Lair Marie-Lise

Subjects
Epidemiology, Population-based study, Nested case-control cohort, Aging, Cognition, Mild cognitive impairment, Alzheimer’s disease, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. Methods/design The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. Discussion By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole.

Published
2012
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8. Health and aging in elderly farmers: the AMI cohort

Author

Pérès Karine, Matharan Fanny, Allard Michèle, Amieva Hélène, Baldi Isabelle, Barberger-Gateau Pascale, Bergua Valérie, Bourdel-Marchasson Isabelle, Delcourt Cécile, Foubert-Samier Alexandra, Fourrier-Réglat Annie, Gaimard Maryse, Laberon Sonia, Maubaret Cécilia, Postal Virginie, Chantal Chantal, Rainfray Muriel, Rascle Nicole, and Dartigues Jean-François

Subjects
Aging, Rural health, Agriculture, Cohort studies, Interdisciplinary studies, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The health of the agricultural population has been previously explored, particularly in relation to the farming exposures and among professionally active individuals. However, few studies specifically focused on health and aging among elders retired from agriculture. Yet, this population faces the long-term effects of occupational exposures and multiple difficulties related to living and aging in rural area (limited access to shops, services, and practitioners). However, these difficulties may be counter-balanced by advantages related to healthier lifestyle, richer social support and better living environment. The general aim of the AMI cohort was to study health and aging in elderly farmers living in rural area through a multidisciplinary approach, with a main focus on dementia. Methods/design The study initially included 1 002 participants, randomly selected from the Farmer Health Insurance rolls. Selection criteria were: being 65 years and older; living in rural area in Gironde (South-Western France); being retired from agriculture after at least 20 years of activity and being affiliated to the Health Insurance under own name. The study started in 2007, with two follow-up visits over 5 years. Baseline visits were conducted at home by a neuropsychologist then by a geriatrician for all cases suspected of dementia, Parkinson’s disease and depression (to confirm the diagnosis), and by a nurse for others. A large panel of data were collected through standardised questionnaires: complete neuropsychological assessment, material and social living environment, psychological transition to retirement, lifestyle (smoking, alcohol and diet), medications, disability in daily living, sensory impairments and some clinical measures (blood pressure, depression symptomatology, anxiety, visual test, anthropometry…). A blood sampling was performed with biological measurements and constitution of a biological bank, including DNA. Brain MRI were also performed on 316 of the participants. Finally, the three-year data on health-related reimbursements were extracted from the Health System database (medications, medical and paramedical consultations, biological examinations and medical devices), and the registered Long-Term Diseases (30 chronic diseases 100% covered by the Insurance System). Discussion AMI is the first French longitudinal study on health and aging set up in a population of elderly farmers living in rural area through a multidisciplinary approach.

Published
2012
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9. Inappropriate medication use and risk of falls – A prospective study in a large community-dwelling elderly cohort

Author

Fourrier Annie, Dartigues Jean-François, Bertrand Marion, Berdot Sarah, Tavernier Béatrice, Ritchie Karen, and Alpérovitch Annick

Subjects
Geriatrics, RC952-954.6
Abstract

Abstract Background Explicit criteria for determining potentially inappropriate medication consumption in elderly were elaborated by Beers et al. These lists have been used worldwide to evaluate medical prescriptions but there is little epidemiologic evidence demonstrating negative consequences of inappropriate medication use. It has been reported that some drugs could increase the risk of falls, which are a frequent and serious problem in elderly population. We aimed to evaluate the association between the use of potentially inappropriate medications and the risk of falls. Methods The 3C Study is a multicentre prospective cohort study conducted in France with 4 years of follow-up. Non-institutionalized men and women aged 65 years or over (N = 6343) were randomly selected from electoral rolls. Data on socio-demographic, medical characteristics and medication use (based on self-reports and data from the national healthcare insurance) were collected. Use of inappropriate medication for elderly was defined from established criteria. Data about falls were collected at the two follow-up examinations (2 years and 4 years after baseline). The association between the exposure to inappropriate medications and the risk of falls was evaluated using multivariate models (Cox model and logistic regression). Results 32% of subjects reported inappropriate medication use at baseline and 29% at least two of the three examinations; 22% had fallen 2 times or more during follow-up. Overall, inappropriate medication users had an increased risk of falling. This increase was mainly due to the use of long-acting benzodiazepines (adjusted odds ratio (OR) = 1.4, 95% confidence interval: [1.1–1.8], in both occasional and regular users), other inappropriate psychotropics (adjusted OR = 1.7 [1.7–2.7] in regular users), or medication with anticholinergic properties (adjusted OR = 1.6 [1.2–2.1] in regular users). Neither occasional, nor regular use of short- or intermediate-acting benzodiazepines was associated with an increased risk of falling. Further analysis in long-acting benzodiazepines users did not show any dose-effect relation between the number of prescriptions filled over a 3-year period and the risk of falling. Conclusion Our study showed that use of inappropriate medications was associated with an increased risk of falling in elderly persons. This increase was mainly due to long-acting benzodiazepines and other inappropriate psychotropics, and to medications with anticholinergic properties.

Published
2009
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10. Dynamic Modelling of Multivariate Dimensions and Their Temporal Relationships using Latent Processes: Application to Alzheimer's Disease

Author

Taddé, Bachirou O., Jacqmin-Gadda, Hélène, Dartigues, Jean-François, Commenges, Daniel, and Proust-Lima, Cécile

Subjects
Statistics - Applications
Abstract

Alzheimer's disease gradually affects several components including the cerebral dimension with brain atrophies, the cognitive dimension with a decline in various functions and the functional dimension with impairment in the daily living activities. Understanding how such dimensions interconnect is crucial for AD research. However it requires to simultaneously capture the dynamic and multidimensional aspects, and to explore temporal relationships between dimensions. We propose an original dynamic structural model that accounts for all these features. The model defines dimensions as latent processes and combines a multivariate linear mixed model and a system of difference equations to model trajectories and temporal relationships between latent processes in finely discrete time. Dimensions are simultaneously related to their observed (possibly multivariate) markers through nonlinear equations of observation. Parameters are estimated in the maximum likelihood framework enjoying a closed form for the likelihood. We demonstrate in a simulation study that this dynamic model in discrete time benefits the same causal interpretation of temporal relationships as models defined in continuous time as long as the discretization step remains small. The model is then applied to the data of the Alzheimer's Disease Neuroimaging Initiative. Three longitudinal dimensions (cerebral anatomy, cognitive ability and functional autonomy) measured by 6 markers are analyzed and their temporal structure is contrasted between different clinical stages of Alzheimer's disease. Keywords: causality, difference equations, latent process, longitudinal data, mixed models, multivariate data.

Published
2018
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11. A joint model for multiple dynamic processes and clinical endpoints: application to Alzheimer's disease

Author

Proust-Lima, Cécile, Philipps, Viviane, and Dartigues, Jean-François

Subjects
Statistics - Methodology
Abstract

As other neurodegenerative diseases, Alzheimer's disease, the most frequent dementia in the elderly, is characterized by multiple progressive impairments in the brain structure and in clinical functions such as cognitive functioning and functional disability. Until recently, these components were mostly studied independently since no joint model for multivariate longitudinal data and time to event was available in the statistical community. Yet, these components are fundamentally inter-related in the degradation process towards dementia and should be analyzed together. We thus propose a joint model to simultaneously describe the dynamics of multiple correlated components. Each component, defined as a latent process, is measured by one or several continuous markers (not necessarily Gaussian). Rather than considering the associated time to diagnosis as in standard joint models, we assume diagnosis corresponds to the passing above a covariate-specific threshold (to be estimated) of a pathological process which is modelled as a combination of the component-specific latent processes. This definition captures the clinical complexity of diagnoses such as dementia diagnosis but also benefits from simplifications for the computation of Maximum Likelihood Estimates. We show that the model and estimation procedure can also handle competing clinical endpoints. The estimation procedure, implemented in a R package, is validated by simulations and the method is illustrated on a large French population-based cohort of cerebral aging in which we focused on the dynamics of three clinical manifestations and the associated risk of dementia and death before dementia.

Published
2018
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12. Genome‐wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy

Author

Chen, Zhongbo, Chen, Jason A, Shatunov, Aleksey, Jones, Ashley R, Kravitz, Stephanie N, Huang, Alden Y, Lawrence, Lauren, Lowe, Jennifer K, Lewis, Cathryn M, Payan, Christine AM, Lieb, Wolfgang, Franke, Andre, Deloukas, Panagiotis, Amouyel, Philippe, Tzourio, Christophe, Dartigues, Jean‐François, Groups, NNIPPS and BBBIPPS Study, Ludolph, Albert, Bensimon, Gilbert, Leigh, P Nigel, Bronstein, Jeff M, Coppola, Giovanni, Geschwind, Daniel H, and Al‐Chalabi, Ammar

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Prevention, Clinical Research, Neurodegenerative, Genetics, Brain Disorders, Rare Diseases, Genetic Testing, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Age of Onset, Aged, Aged, 80 and over, DNA Copy Number Variations, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Supranuclear Palsy, Progressive, tau Proteins, copy number variation, genome-wide association study, progressive supranuclear palsy, NNIPPS and BBBIPPS Study Groups, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundProgressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic-rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome-wide association analysis of a cohort of well-characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes and Blood Brain Barrier in Parkinson Plus Syndromes studies.MethodsWe genotyped single-nucleotide polymorphisms in 283 PSP cases from the United Kingdom, Germany, and France and compared these with genotypes from 4472 controls. Copy number variants were identified from genotyping data.ResultsWe observed associations on chromosome 17 within or close to the MAPT gene and explored the genetic architecture at this locus. We confirmed the previously reported association of rs1768208 in the MOBP gene (P = 3.29 × 10-13 ) and rs1411478 in STX6 (P = 3.45 × 10-10 ). The population-attributable risk from the MAPT, MOBP, and STX6 single-nucleotide polymorphisms was found to be 0.37, 0.26, and 0.08, respectively. In addition, we found 2 instances of copy number variants spanning the MAPT gene in patients with PSP. These copy number variants include tau but few other genes within the chromosome 17 haplotype region, providing additional support for the direct pathogenicity of MAPT in PSP.ConclusionsClinicians should also be aware of MAPT duplication as a possible genetic cause of PSP, especially in patients presenting with young age at onset. © 2019 International Parkinson and Movement Disorder Society.

Published
2019

13. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
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14. Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

Author

Blanc, Frederic, Bouteloup, Vincent, Paquet, Claire, Chupin, Marie, Pasquier, Florence, Gabelle, Audrey, Ceccaldi, Mathieu, de Sousa, Paulo Loureiro, Krolak-Salmon, Pierre, David, Renaud, Fischer, Clara, Dartigues, Jean-François, Wallon, David, Moreaud, Olivier, Sauvée, Mathilde, Belin, Catherine, Harston, Sandrine, Botzung, Anne, Albasser, Timothée, Demuynck, Catherine, Namer, Izzie, Habert, Marie-Odile, Kremer, Stéphane, Bousiges, Olivier, Verny, Marc, Muller, Candice, Philippi, Nathalie, Chene, Geneviève, Cretin, Benjamin, Mangin, Jean-François, and Dufouil, Carole

Published
2022
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19. Joint latent class model for longitudinal data and interval-censored semi-competing events: Application to dementia

Author

Rouanet, Anaïs, Joly, Pierre, Dartigues, Jean-François, Proust-Lima, Cécile, and Jacqmin-Gadda, Hélène

Subjects
Statistics - Methodology
Abstract

Joint models are used in ageing studies to investigate the association between longitudinal markers and a time-to-event, and have been extended to multiple markers and/or competing risks. The competing risk of death must be considered in the elderly because death and dementia have common risk factors. Moreover, in cohort studies, time-to-dementia is interval-censored because dementia is only assessed intermittently. So subjects can become demented and die between two follow-up visits without being diagnosed. To study pre-dementia cognitive decline, we propose a joint latent class model combining a (possibly multivariate) mixed model and an illness-death model handling both interval censoring (by accounting for a possible unobserved transition to dementia) and semi-competing risks. Parameters are estimated by maximum likelihood handling interval censoring. The correlation between the marker and the times-to-events is captured by latent classes, homogeneous groups with specific risks of death and dementia and profiles of cognitive decline. We propose markovian and semi-markovian versions. Both approaches are compared to a joint latent class model for standard competing risks through a simulation study, and then applied in a prospective cohort study of cerebral and functional ageing to distinguish different profiles of cognitive decline associated with risks of dementia and death. The comparison highlights that among demented subjects, mortality depends more on age than duration of dementia. This model distinguishes the so-called terminal pre-death decline (among non-demented subjects) from the pre-dementia decline.

Published
2015
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20. Malnutrition and its determinants among older adults living in foster families in Guadeloupe (French West Indies). A cross-sectional study.

Author

Boucaud-Maitre, Denis, Simo-Tabue, Nadine, Mounsamy, Ludwig, Rambhojan, Christine, Letchimy, Laurys, Rinaldo, Leila, Dartigues, Jean-François, Amieva, Hélène, Dramé, Moustapha, and Tabué-Teguo, Maturin

Subjects
FOSTER parents, OLDER people, NUTRITIONAL status, MALNUTRITION, ALZHEIMER'S disease, CROSS-sectional method, NUTRITIONAL assessment
Abstract

Background: Foster families may represent an alternative model for dependent older adults in many countries where nursing homes are insufficiently developed. This study aimed to assess the prevalence of malnutrition and its determinants in older adults living in foster families in Guadeloupe (French West Indies). Methods: This cross-sectional study was gathered from the KASAF (Karukera Study of Ageing in Foster families) study (n = 107, 41M/66F, Mdn 81.8 years). Nutritional status was assessed with the Mini Nutritional Assessment Short‐Form (MNA‐SF). Clinical characteristics and scores on geriatric scales (Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB), Center for Epidemiologic Studies- Depression (CESD) and Questionnaire Quality of Life Alzheimer's Disease (QoL-AD)) were extracted. Bivariate analysis and logistic models adjusted for age and gender were performed to test the association of nutritional status with socio-demographic variables and geriatric scales. Results: Thirty (28.0%) older adults were malnourished (MNA-SF score ≤7). In bivariate analysis, malnutrition was associated with an increased prevalence of cardiovascular diseases (46.7% versus 19.5%, p = 0.004), the presence of hemiplegia (30.0% versus 6.5%, p = 0.003), a poorer cognitive status (MMSE score 4.7 ± 7.1versus 9.7 ± 10.7; p = 0.031), higher risk of depression (CESD score 27.3 ± 23.0 versus 13.5 ± 14.4; p = 0.035) and dependency (ADL score 1.9 ± 1.9 versus 2.3 ± 2.1; p<0.001). Malnutrition was also associated with lower caregivers'rating of QoL (QoL-AD score 21.8 ± 6.4 versus 26.0 ± 5.7; p = 0.001) but not by older adult's rating (24.1 ± 11.2 versus 28.3 ± 7.7; p = 0.156). Similar associations were observed in logistic models adjusted for age and gender. Conclusion: Malnutrition was common among foster families for older adults. Special attention towards the prevention and treatment of malnutrition in older adults from cardiovascular diseases, cognitive impairment, dependency and depression is necessary in this model of dependency support. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts

Author

Campion, Dominique, Dartigues, Jean-Francois, Deleuze, Jean-François, Genin, Emmanuelle, Lambert, Jean-Charles, Redon, Richard, Allain-Launay, Emma, Bader-Meunier, Brigitte, Belot, Alexandre, Bouayed, Kenza, Burtey, Stephane, Carbasse, Aurélia, Decramer, Stéphane, Despert, Véronique, Fain, Olivier, Fischbach, Michel, Flodrops, Hugues, Galeotti, Caroline, Hachulla, Eric, Hatchuel, Yves, Kleinmann, Jean-Francois, Kone-Paut, Isabelle, Lanteri, Aurélia, Lemelle, Irène, Maillard, Hélène, Maurier, François, Meinzer, Ulrich, Melki, Isabelle, Morell-Dubois, Sandrine, Pagnier, Anne, Piram, Maryam, Ranchin, Bruno, Reumaux, Héloise, Samaille, Charlotte, Sibilia, Jean, Weill, Olivia, Al-Abadi, Eslam, Armon, Kate, Bailey, Kathryn, Beresford, Michael, Brennan, Mary, Ciurtin, Coziana, Gardner-Medwin, Janet, Haslam, Kirsty, Hawley, Daniel, Leahy, Alice, Leone, Valentina, Mewar, Devesh, Moots, Rob, Pilkington, Clarissa, Ramanan, Athimalaipet, Rangaraj, Satyapal, Ratcliffe, Annie, Riley, Philip, Sen, Ethan, Sridhar, Arani, Wilkinson, Nick, Wood, Fiona, Rice, Gillian I, Omarjee, Sulliman Ommar, Rouchon, Quentin, Smith, Eve M D, Moreews, Marion, Tusseau, Maud, Frachette, Cécile, Bournhonesque, Raphael, Thielens, Nicole, Gaboriaud, Christine, Rouvet, Isabelle, Chopin, Emilie, Hoshino, Akihiro, Latour, Sylvain, Cimaz, Rolando, Romagnani, Paula, Malcus, Christophe, Fabien, Nicole, Sarda, Marie-Nathalie, Kassai, Behrouz, Lega, Jean-Christophe, Abou-Jaoude, Pauline, Bruce, Ian N, Simonet, Thomas, Bardel, Claire, Rollat-Farnier, Pierre Antoine, Viel, Sebastien, O'Sullivan, James, Walzer, Thierry, Mathieu, Anne-Laure, Marenne, Gaelle, Ludwig, Thomas, Ellingford, Jamie, Briggs, Tracy A, Beresford, Michael W, and Crow, Yanick J

Published
2020
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25. Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial

Author

Coley, Nicola, primary, Zetterberg, Henrik, additional, Cantet, Christelle, additional, Guyonnet, Sophie, additional, Ashton, Nicholas J, additional, Vellas, Bruno, additional, Blennow, Kaj, additional, Andrieu, Sandrine, additional, Carrié, Isabelle, additional, Brigitte, Lauréane, additional, Faisant, Catherine, additional, Lala, Françoise, additional, Delrieu, Julien, additional, Villars, Hélène, additional, Combrouze, Emeline, additional, Badufle, Carole, additional, Zueras, Audrey, additional, Morin, Christophe, additional, Abellan Van Kan, Gabor, additional, Dupuy, Charlotte, additional, Rolland, Yves, additional, Caillaud, Céline, additional, Ousset, Pierre-Jean, additional, Willis, Sherry, additional, Belleville, Sylvie, additional, Gilbert, Brigitte, additional, Fontaine, Francine, additional, Dartigues, Jean-François, additional, Marcet, Isabelle, additional, Delva, Fleur, additional, Foubert, Alexandra, additional, Cerda, Sandrine, additional, Cuffi, Marie-Noëlle, additional, Costes, Corinne, additional, Rouaud, Olivier, additional, Manckoundia, Patrick, additional, Quipourt, Valérie, additional, Marilier, Sophie, additional, Franon, Evelyne, additional, Bories, Lawrence, additional, Pader, Marie-Laure, additional, Basset, Marie-France, additional, Lapoujade, Bruno, additional, Faure, Valérie, additional, Li Yung Tong, Michael, additional, Malick-Loiseau, Christine, additional, Cazaban-Campistron, Evelyne, additional, Desclaux, Françoise, additional, Blatge, Colette, additional, Dantoine, Thierry, additional, Laubarie-Mouret, Cécile, additional, Saulnier, Isabelle, additional, Clément, Jean-Pierre, additional, Picat, Marie-Agnès, additional, Bernard-Bourzeix, Laurence, additional, Willebois, Stéphanie, additional, Désormais, Iléana, additional, Cardinaud, Noëlle, additional, Bonnefoy, Marc, additional, Livet, Pierre, additional, Rebaudet, Pascale, additional, Gédéon, Claire, additional, Burdet, Catherine, additional, Terracol, Flavien, additional, Pesce, Alain, additional, Roth, Stéphanie, additional, Chaillou, Sylvie, additional, Louchart, Sandrine, additional, Sudres, Kristel, additional, Lebrun, Nicolas, additional, Barro-Belaygues, Nadège, additional, Touchon, Jacques, additional, Bennys, Karim, additional, Gabelle, Audrey, additional, Romano, Aurélia, additional, Touati, Lynda, additional, Marelli, Cécilia, additional, Pays, Cécile, additional, Robert, Philippe, additional, Le Duff, Franck, additional, Gervais, Claire, additional, Gonfrier, Sébastien, additional, Gasnier, Yannick, additional, Bordes, Serge, additional, Begorre, Danièle, additional, Carpuat, Christian, additional, Khales, Khaled, additional, Lefebvre, Jean-François, additional, Misbah El Idrissi, Samira, additional, Skolil, Pierre, additional, Salles, Jean-Pierre, additional, Dufouil, Carole, additional, Lehéricy, Stéphane, additional, Chupin, Marie, additional, Mangin, Jean-François, additional, Bouhayia, Ali, additional, Allard, Michèle, additional, Ricolfi, Frédéric, additional, Dubois, Dominique, additional, Bonceour Martel, Marie Paule, additional, Cotton, François, additional, Bonafé, Alain, additional, Chanalet, Stéphane, additional, Hugon, Françoise, additional, Bonneville, Fabrice, additional, Cognard, Christophe, additional, Chollet, François, additional, Payoux, Pierre, additional, Voisin, Thierry, additional, Peiffer, Sophie, additional, Hitzel, Anne, additional, Zanca, Michel, additional, Monteil, Jacques, additional, Darcourt, Jacques, additional, Molinier, Laurent, additional, Derumeaux, Hélène, additional, Costa, Nadège, additional, Perret, Bertrand, additional, Vinel, Claire, additional, Caspar-Bauguil, Sylvie, additional, Olivier-Abbal, Pascale, additional, and Coley, Nicola, additional

Published
2024
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27. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.

Author

van Rheenen, Wouter, Shatunov, Aleksey, Dekker, Annelot M, McLaughlin, Russell L, Diekstra, Frank P, Pulit, Sara L, van der Spek, Rick AA, Võsa, Urmo, de Jong, Simone, Robinson, Matthew R, Yang, Jian, Fogh, Isabella, van Doormaal, Perry Tc, Tazelaar, Gijs HP, Koppers, Max, Blokhuis, Anna M, Sproviero, William, Jones, Ashley R, Kenna, Kevin P, van Eijk, Kristel R, Harschnitz, Oliver, Schellevis, Raymond D, Brands, William J, Medic, Jelena, Menelaou, Androniki, Vajda, Alice, Ticozzi, Nicola, Lin, Kuang, Rogelj, Boris, Vrabec, Katarina, Ravnik-Glavač, Metka, Koritnik, Blaž, Zidar, Janez, Leonardis, Lea, Grošelj, Leja Dolenc, Millecamps, Stéphanie, Salachas, François, Meininger, Vincent, de Carvalho, Mamede, Pinto, Susana, Mora, Jesus S, Rojas-García, Ricardo, Polak, Meraida, Chandran, Siddharthan, Colville, Shuna, Swingler, Robert, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Pittman, Alan, Sidle, Katie, Fratta, Pietro, Malaspina, Andrea, Topp, Simon, Petri, Susanne, Abdulla, Susanne, Drepper, Carsten, Sendtner, Michael, Meyer, Thomas, Ophoff, Roel A, Staats, Kim A, Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, Van Deerlin, Vivianna M, Trojanowski, John Q, Elman, Lauren, McCluskey, Leo, Basak, A Nazli, Tunca, Ceren, Hamzeiy, Hamid, Parman, Yesim, Meitinger, Thomas, Lichtner, Peter, Radivojkov-Blagojevic, Milena, Andres, Christian R, Maurel, Cindy, Bensimon, Gilbert, Landwehrmeyer, Bernhard, Brice, Alexis, Payan, Christine AM, Saker-Delye, Safaa, Dürr, Alexandra, Wood, Nicholas W, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M, Amouyel, Philippe, Tzourio, Christophe, Dartigues, Jean-François, Uitterlinden, Andre G, Rivadeneira, Fernando, Estrada, Karol, Hofman, Albert, Curtis, Charles, and Blauw, Hylke M

Subjects
PARALS Registry, SLALOM Group, SLAP Registry, FALS Sequencing Consortium, SLAGEN Consortium, NNIPPS Study Group, Humans, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Proteins, Cytoskeletal Proteins, Myelin Proteins, Case-Control Studies, Cohort Studies, Mutation, Netherlands, Munc18 Proteins, Genome-Wide Association Study, Neurosciences, Rare Diseases, Brain Disorders, Biotechnology, Prevention, Human Genome, Neurodegenerative, Genetics, ALS, Aetiology, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.

Published
2016

28. Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Author

Dubois, Bruno, Hampel, Harald, Feldman, Howard H, Scheltens, Philip, Aisen, Paul, Andrieu, Sandrine, Bakardjian, Hovagim, Benali, Habib, Bertram, Lars, Blennow, Kaj, Broich, Karl, Cavedo, Enrica, Crutch, Sebastian, Dartigues, Jean-François, Duyckaerts, Charles, Epelbaum, Stéphane, Frisoni, Giovanni B, Gauthier, Serge, Genthon, Remy, Gouw, Alida A, Habert, Marie-Odile, Holtzman, David M, Kivipelto, Miia, Lista, Simone, Molinuevo, José-Luis, O'Bryant, Sid E, Rabinovici, Gil D, Rowe, Christopher, Salloway, Stephen, Schneider, Lon S, Sperling, Reisa, Teichmann, Marc, Carrillo, Maria C, Cummings, Jeffrey, Jack, Cliff R, Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on “The Preclinical State of AD”, July 23, 2015, and Washington DC, USA

Subjects
Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on “The Preclinical State of AD”, July 23, 2015, Washington DC, USA, Brain, Animals, Humans, Alzheimer Disease, Disease Progression, Alzheimer's disease, Amyloid PET, Asymptomatic, Biomarkers, Blood biomarkers, CSF biomarkers, Diagnostic criteria, Genetics, MRI, Pathophysiology, Preclinical, Tau PET, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Dementia, Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Human Genome, Neurosciences, Neurological, Clinical Sciences, Geriatrics
Abstract

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Published
2016

29. Joint modelling of repeated multivariate cognitive measures and competing risks of dementia and death: a latent process and latent class approach

Author

Proust-Lima, Cécile, Dartigues, Jean-François, and Jacqmin-Gadda, Hélène

Subjects
Statistics - Applications
Abstract

Joint models initially dedicated to a single longitudinal marker and a single time-to-event need to be extended to account for the rich longitudinal data of cohort studies. Multiple causes of clinical progression are indeed usually observed, and multiple longitudinal markers are collected when the true latent trait of interest is hard to capture (e.g. quality of life, functional dependency, cognitive level). These multivariate and longitudinal data also usually have nonstandard distributions (discrete, asymmetric, bounded,...). We propose a joint model based on a latent process and latent classes to analyze simultaneously such multiple longitudinal markers of different natures, and multiple causes of progression. A latent process model describes the latent trait of interest and links it to the observed longitudinal outcomes using flexible measurement models adapted to different types of data, and a latent class structure links the longitudinal and the cause-specific survival models. The joint model is estimated in the maximum likelihood framework. A score test is developed to evaluate the assumption of conditional independence of the longitudinal markers and each cause of progression given the latent classes. In addition, individual dynamic cumulative incidences of each cause of progression based on the repeated marker data are derived. The methodology is validated in a simulation study and applied on real data about cognitive aging coming from a large population-based study. The aim is to predict the risk of dementia by accounting for the competing death according to the profiles of semantic memory measured by two asymmetric psychometric tests.

Published
2014
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34. The genetic history of France

Author

Saint Pierre, Aude, Giemza, Joanna, Alves, Isabel, Karakachoff, Matilde, Gaudin, Marinna, Amouyel, Philippe, Dartigues, Jean-François, Tzourio, Christophe, Monteil, Martial, Galan, Pilar, Hercberg, Serge, Mathieson, Iain, Redon, Richard, Génin, Emmanuelle, and Dina, Christian

Published
2020
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35. Egocentric vision IT technologies for Alzheimer disease assessment and studies

Author

Boujut, Hugo, Buso, Vincent, Bourmaud, Guillaume, Benois-Pineau, Jenny, Mégret, Rémi, Domenger, Jean-Philippe, Gaëstel, Yann, and Dartigues, Jean-François

Subjects
Computer Science - Human-Computer Interaction, Computer Science - Computer Vision and Pattern Recognition
Abstract

Egocentric vision technology consists in capturing the actions of persons from their own visual point of view using wearable camera sensors. We apply this new paradigm to instrumental activities monitoring with the objective of providing new tools for the clinical evaluation of the impact of the disease on persons with dementia. In this paper, we introduce the current state of the development of this technology and focus on two technology modules: automatic location estimation and visual saliency estimation for content interpretation., Comment: RITS - Recherche en Imagerie et Technologies pour la Sant\'e, France (2013)

Published
2013

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

Author

Richard, Edo, van Gool, Pim, van Charante, Eric Moll, Beishuizen, Cathrien, Jongstra, Susan, van Middelaar, Tessa, van Wanrooij, Lennard, Hoevenaar-Blom, Marieke, Soininen, Hilkka, Ngandu, Tiia, Barbera, Mariagnese, Kivipelto, Miia, Mangiasche, Francesca, Andrieu, Sandrine, Coley, Nicola, Guillemont, Juliette, Meiller, Yannick, van de Groep, Bram, Brayne, Carol, Solomon, Alina, Laatikainen, Tiina, Strandberg, Timo, Tuomilehto, Jaakko, Antikainen, Riitta, Lindström, Jaana, Lehtisalo, Jenni, Havulinna, Satu, Rauramaa, Rainer, Hänninen, Tuomo, Bäckman, Lars, Stigsdotter-Neely, Anna, Jula, Antti, Peltonen, Markku, Levälahti, Esko, Grönholm, Marko, Hemiö, Katri, Vellas, Bruno, Guyonnet, Sophie, Carrié, Isabelle, Brigitte, Lauréane, Faisant, Catherine, Lala, Françoise, Delrieu, Julien, Villars, Hélène, Combrouze, Emeline, Badufle, Carole, Zueras, Audrey, Cantet, Christelle, Morin, Christophe, Van Kan, Gabor Abellan, Dupuy, Charlotte, Rolland, Yves, Caillaud, Céline, Ousset, Pierre-Jean, Fougère, Bertrand, Willis, Sherry, Belleville, Sylvie, Gilbert, Brigitte, Fontaine, Francine, Dartigues, Jean-François, Marcet, Isabelle, Delva, Fleur, Foubert, Alexandra, Cerda, Sandrine, Marie-Noëlle-Cuffi, Costes, Corinne, Rouaud, Olivier, Manckoundia, Patrick, Quipourt, Valérie, Marilier, Sophie, Franon, Evelyne, Bories, Lawrence, Pader, Marie-Laure, Basset, Marie-France, Lapoujade, Bruno, Faure, Valérie, Yung Tong, Michael Li, Malick-Loiseau, Christine, Cazaban-Campistron, Evelyne, Desclaux, Françoise, Blatge, Colette, Dantoine, Thierry, Laubarie-Mouret, Cécile, Saulnier, Isabelle, Clément, Jean-Pierre, Picat, Marie-Agnès, Bernard-Bourzeix, Laurence, Willebois, Stéphanie, Désormais, Iléana, Cardinaud, Noëlle, Bonnefoy, Marc, Livet, Pierre, Rebaudet, Pascale, Gédéon, Claire, Burdet, Catherine, Terracol, Flavien, Pesce, Alain, Roth, Stéphanie, Chaillou, Sylvie, Louchart, Sandrine, Sudres, Kristelle, Lebrun, Nicolas, Barro-Belaygues, Nadège, Touchon, Jacques, Bennys, Karim, Gabelle, Audrey, Romano, Aurélia, Touati, Lynda, Marelli, Cécilia, Pays, Cécile, Robert, Philippe, Le Duff, Franck, Gervais, Claire, Gonfrier, Sébastien, Gasnier, Yannick, Bordes, Serge, Begorre, Danièle, Carpuat, Christian, Khales, Khaled, Lefebvre, Jean-François, El Idrissi, Samira Misbah, Skolil, Pierre, Salles, Jean-Pierre, Dufouil, Carole, Lehéricy, Stéphane, Chupin, Marie, Mangin, Jean-François, Bouhayia, Ali, Allard, Michèle, Ricolfi, Frédéric, Dubois, Dominique, Bonceour Martel, Marie Paule, Cotton, François, Bonafé, Alain, Chanalet, Stéphane, Hugon, Françoise, Bonneville, Fabrice, Cognard, Christophe, Chollet, François, Payoux, Pierre, Voisin, Thierry, Peiffer, Sophie, Hitzel, Anne, Zanca, Michel, Monteil, Jacques, Darcourt, Jacques, Molinier, Laurent, Derumeaux, Hélène, Costa, Nadège, Vincent, Christian, Perret, Bertrand, Vinel, Claire, and Olivier-Abbal, Pascale

Published
2019
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39. Hierarchical Hidden Markov Model in Detecting Activities of Daily Living in Wearable Videos for Studies of Dementia

Author

Karaman, Svebor, Benois-Pineau, Jenny, Dovgalecs, Vladislavs, Mégret, Rémi, Pinquier, Julien, André-Obrecht, Régine, Gaëstel, Yann, and Dartigues, Jean-François

Subjects
Computer Science - Multimedia
Abstract

This paper presents a method for indexing activities of daily living in videos obtained from wearable cameras. In the context of dementia diagnosis by doctors, the videos are recorded at patients' houses and later visualized by the medical practitioners. The videos may last up to two hours, therefore a tool for an efficient navigation in terms of activities of interest is crucial for the doctors. The specific recording mode provides video data which are really difficult, being a single sequence shot where strong motion and sharp lighting changes often appear. Our work introduces an automatic motion based segmentation of the video and a video structuring approach in terms of activities by a hierarchical two-level Hidden Markov Model. We define our description space over motion and visual characteristics of video and audio channels. Experiments on real data obtained from the recording at home of several patients show the difficulty of the task and the promising results of our approach.

Published
2011
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40. Activities of Daily Living Indexing by Hierarchical HMM for Dementia Diagnostics

Author

Karaman, Svebor, Benois-Pineau, Jenny, Dartigues, Jean-François, Gaëstel, Yann, Mégret, Rémi, and Pinquier, Julien

Subjects
Computer Science - Multimedia
Abstract

This paper presents a method for indexing human ac- tivities in videos captured from a wearable camera being worn by patients, for studies of progression of the dementia diseases. Our method aims to produce indexes to facilitate the navigation throughout the individual video recordings, which could help doctors search for early signs of the dis- ease in the activities of daily living. The recorded videos have strong motion and sharp lighting changes, inducing noise for the analysis. The proposed approach is based on a two steps analysis. First, we propose a new approach to segment this type of video, based on apparent motion. Each segment is characterized by two original motion de- scriptors, as well as color, and audio descriptors. Second, a Hidden-Markov Model formulation is used to merge the multimodal audio and video features, and classify the test segments. Experiments show the good properties of the ap- proach on real data., Comment: 2011 9th International Workshop on Content-Based Multimedia Indexing (CBMI), Madrid : Spain (2011)

Published
2011
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41. Human Daily Activities Indexing in Videos from Wearable Cameras for Monitoring of Patients with Dementia Diseases

Author

Karaman, Svebor, Benois-Pineau, Jenny, Mégret, Rémi, Dovgalecs, Vladislavs, Dartigues, Jean-François, and Gaëstel, Yann

Subjects
Computer Science - Multimedia, Statistics - Machine Learning
Abstract

Our research focuses on analysing human activities according to a known behaviorist scenario, in case of noisy and high dimensional collected data. The data come from the monitoring of patients with dementia diseases by wearable cameras. We define a structural model of video recordings based on a Hidden Markov Model. New spatio-temporal features, color features and localization features are proposed as observations. First results in recognition of activities are promising.

Published
2010
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42. Estimating long‐term multivariate progression from short‐term data

Author

Donohue, Michael C, Jacqmin‐Gadda, Hélène, Le Goff, Mélanie, Thomas, Ronald G, Raman, Rema, Gamst, Anthony C, Beckett, Laurel A, Jack, Clifford R, Weiner, Michael W, Dartigues, Jean‐François, and Aisen, Paul S

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Acquired Cognitive Impairment, Bioengineering, Brain Disorders, Alzheimer's Disease, Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Algorithms, Alzheimer Disease, Computer Simulation, Databases, Factual, Disease Progression, Humans, Models, Biological, Multivariate Analysis, Prognosis, Software, Multiple outcomes, Semiparametric regression, Self-modeling regression, Progression curves, Growth curves, Geriatrics, Clinical sciences, Biological psychology
Abstract

Motivation: Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes Agées Quid" study. Results: We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Availability: Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging. © 2014 The Alzheimer's Association.

Published
2014

43. The role of cardiovascular health and vascular events in the relationship between excessive daytime sleepiness and dementia risk.

Author

Cavaillès, Clémence, Letellier, Noémie, Berr, Claudine, Samieri, Cecilia, Empana, Jean‐Philippe, Tzourio, Christophe, Dartigues, Jean‐François, Benmarhnia, Tarik, Dauvilliers, Yves, and Jaussent, Isabelle

Subjects
DROWSINESS, DISEASE risk factors, ALZHEIMER'S disease, VASCULAR dementia, OLDER people, DEMENTIA
Abstract

Summary: Many studies suggest a relationship between excessive daytime sleepiness (EDS) and dementia incidence, but the underlying mechanisms remain uncertain. The study aimed to investigate the role of cardiovascular burden in the relationship between EDS and dementia incidence over a 12‐year follow‐up in community‐dwelling older adults. We performed analyses on 6171 subjects (aged ≥65 years) free of dementia and vascular disease at baseline. Participants self‐reported EDS at baseline and an expert committee validated both prevalent and incident dementia. We defined cardiovascular burden by a low Cardiovascular Health score, constructed using the American Heart Association metrics, and incident vascular events. To explore the potential role of the cardiovascular burden in the relationship between EDS and dementia, we conducted mediation analyses with inverse odds ratio‐weighted estimation, using multivariable‐adjusted proportional hazard Cox and logistic regression models. Subjects with EDS had a higher risk of all‐cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13–1.69) and dementia with vascular component (DVC) (HR 2.14, 95% CI 1.30–3.51), but not Alzheimer's disease (HR 1.18, 95% CI 0.93–1.51). Cardiovascular burden explained 5% (95% CI 4.1–5.2) and 11% (95% CI 9.7–11.3) of the relationship between EDS and all‐cause dementia and DVC, respectively. These findings confirm that EDS may be implicated in the development of dementia and indicate a weaker than expected role of cardiovascular burden in the relationship between EDS and DVC. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Transferability of a European-derived Alzheimer’s Disease Genetic Risk Score across Multi-Ancestry Populations

Author

Nicolas, Aude, primary, Grenier-Boley, Benjamin, additional, Sherva, Richard, additional, Kim, Yoontae, additional, Kikuchi, Masataka, additional, de Rojas, Itziar, additional, Dalmasso, Carolina, additional, Zhou, Xiaopu, additional, Guen, Yann Le, additional, Arboleda-Bustos, Carlos E, additional, Camargos Bicalho, Maria Aparecida, additional, Guerchet, Maëlenn, additional, van der Lee, Sven, additional, Goss, Monica, additional, Castillo, Atahualpa, additional, Bellenguez, Céline, additional, Küçükali, Fahri, additional, Satizabal Barrera, Claudia, additional, Fongang, Bernard, additional, yang, Qiong, additional, Peters, Oliver, additional, Schneider, Anja, additional, Dichgans, Martin, additional, Rujescu, Dan, additional, Scherbaum, Norbert, additional, Deckert, Jürgen, additional, Riedel-Heller, Steffi, additional, Hausner, Lucrezia, additional, Molina Porcel, Laura, additional, Düzel, Emrah, additional, Grimmer, Timo, additional, Wiltfang, Jens, additional, Heilmann-Heimbach, Stefanie, additional, Moebus, Susanne, additional, Tegos, Thomas, additional, Scarmeas, Nikolaos, additional, Dols-Icardo, Oriol, additional, Moreno, Fermin, additional, Pérez-Tur, Jordi, additional, Bullido, María J., additional, Pastor, Pau, additional, Sánchez-Valle, Raquel, additional, Álvarez, Victoria, additional, Cao, Han, additional, Ip, Nancy Y., additional, Fu, Amy K. Y., additional, Ip, Fanny C. F., additional, Olivar, Natividad, additional, Muchnik, Carolina, additional, Cuesta, Carolina, additional, Campanelli, Lorenzo, additional, Solis, Patricia, additional, Politis, Daniel Gustavo, additional, Kochen, Silvia, additional, Brusco, Luis Ignacio, additional, Boada, Mercè, additional, García-González, Pablo, additional, Puerta, Raquel, additional, Mir, Pablo, additional, Real, Luis M, additional, Piñol-Ripoll, Gerard, additional, María García-Alberca, Jose, additional, Luís Royo, Jose, additional, Rodriguez-Rodriguez, Eloy, additional, Soininen, Hilkka, additional, Heikkinen, Sami, additional, de Mendonça, Alexandre, additional, Mehrabian, Shima, additional, Traykov, Latchezar, additional, Hort, Jakub, additional, Vyhnalek, Martin, additional, Rasmussen, Katrine Laura, additional, Qvist Thomassen, Jesper, additional, Pijnenburg, Yolande A.L., additional, Holstege, Henne, additional, van Swieten, John, additional, Ramakers, Inez, additional, Verhey, Frans, additional, van der Lugt, Aad, additional, Scheltens, Philip, additional, Ortega-Rojas, Jenny, additional, Concha Mera, Ana Gabriela, additional, Mahecha, Maria F., additional, Pardo, Rodrogo, additional, Arboleda, Gonzalo, additional, Graff, Caroline, additional, Papenberg, Goran, additional, Giedraitis, Vilmantas, additional, Boland, Anne, additional, Deleuze, Jean-François, additional, Armando de Marco, Luiz, additional, Nunes de Moraes, Edgar, additional, de Viana, Bernardo, additional, Túlio Gualberto Cintra, Marco, additional, Grsiwold, Anthony, additional, Forund, Tatiana, additional, Cruchaga, Carlos, additional, Haines, Jonathan, additional, Farrer, Lindsay, additional, DeStefano, Anita, additional, Wijsman, Ellen, additional, Mayeux, Richard, additional, Pericak-Vance, Margaret, additional, Kunkle, Brian, additional, Goate, Alison, additional, Schellenberg, Gerard D., additional, Vardarajan, Badri, additional, Wang, Li-San, additional, Leung, Yuk Yee, additional, Dalgard, Clifton, additional, Nicolas, Gael, additional, Wallon, David, additional, Dufouil, Carole, additional, Pasquier, Florence, additional, Hanon, Olivier, additional, Debette, Stéphanie, additional, Grünblatt, Edna, additional, Popp, Julius, additional, Angel, Bárbara, additional, Golger, Sergio, additional, Victoria Chacon, Maria, additional, Aranguiz, Rafael, additional, Orellana, Paulina, additional, Slachevsky, Andrea, additional, Gonzalez-Billault, Christian, additional, Albala, Cecilia, additional, Fuentes, Patricio, additional, Porter, Tenielle, additional, Laws, Simon M, additional, Sachdev, Perminder, additional, Mather, Karen, additional, Hauger, Richard L., additional, Merritt, Victoria, additional, Panizzon, Matthew, additional, Zhang, Rui, additional, Gaziano, Michael, additional, Ghidoni, Roberta, additional, Galimberti, Daniela, additional, Arosio, Beatrice, additional, Mecocci, Patrizia, additional, Solfrizzi, Vincenzo, additional, Parnetti, Lucilla, additional, Squassina, Alessio, additional, Tremolizzo, Lucio, additional, Borroni, Barbara, additional, Nacmias, Benedetta, additional, Caffarra, Paolo, additional, Seripa, Davide, additional, Rainero, Innocenzo, additional, Daniele, Antonio, additional, Piras, Fabrizio, additional, Miyashita, Akinori, additional, Hara, Norikazu, additional, Ozaki, Kouichi, additional, Niida, Shumpei, additional, Williams, Julie, additional, Masullo, Carlo, additional, Amouyel, Philippe, additional, Preux, Pierre-Marie, additional, Mbelesso, Pascal, additional, Bandzouzi, Bébène, additional, Saykin, Andy, additional, Jessen, Frank, additional, Kehoe, Patrick, additional, Van Duijn, Cornelia, additional, Gim, Jungsoo, additional, Ben Salem, Nesrine, additional, Frikke-Schmidt, Ruth, additional, Cherni, Lofti, additional, Greicius, Michael D., additional, Tsolaki, Magda, additional, Sánchez-Juan, Pascual, additional, Romano Silva, Marco Aurélio, additional, Sleegers, Kristel, additional, Ingelsson, Martin, additional, Dartigues, Jean-François, additional, Seshadri, Sudha, additional, Rossi, Giacomina, additional, Morelli, Laura, additional, Hiltunen, Mikko, additional, Sims, Rebecca, additional, van der Flier, Wiesje, additional, Andreassen, Ole, additional, Arboleda, Humberto, additional, Escott-Price, Valentina, additional, Ruiz, Agustín, additional, Lee, Kun Ho, additional, Ikeuchi, Takeshi, additional, Ramirez, Alfredo, additional, Logue, Mark, additional, and Lambert, Jean-Charles, additional

Published
2023
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45. The role of cardiovascular health and vascular events in the relationship between excessive daytime sleepiness and dementia risk

Author

Cavaillès, Clémence, primary, Letellier, Noémie, additional, Berr, Claudine, additional, Samieri, Cecilia, additional, Empana, Jean‐Philippe, additional, Tzourio, Christophe, additional, Dartigues, Jean‐François, additional, Benmarhnia, Tarik, additional, Dauvilliers, Yves, additional, and Jaussent, Isabelle, additional

Published
2023
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46. The PAQUID study

Author

Fabrigoule, Colette, primary, Barberger-Gateau, Pascale, additional, and Dartigues, Jean-François, additional

Published
2019
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47. Red blood cell membrane omega-3 fatty acid levels and physical performance: Cross-sectional data from the MAPT study

Author

Vellas, Bruno, Guyonnet, Sophie, Carrié, Isabelle, Brigitte, Lauréane, Faisant, Catherine, Lala, Françoise, Delrieu, Julien, Villars, Hélène, Combrouze, Emeline, Badufle, Carole, Zueras, Audrey, Andrieu, Sandrine, Cantet, Christelle, Morin, Christophe, Van Kan, Gabor Abellan, Dupuy, Charlotte, Rolland, Yves, Caillaud, Céline, Ousset, Pierre-Jean, Fougère, Bertrand, Willis, Sherry, Belleville, Sylvie, Gilbert, Brigitte, Fontaine, Francine, Dartigues, Jean-François, Marcet, Isabelle, Delva, Fleur, Foubert, Alexandra, Marie-Noëlle-Cuffi, Sandrine Cerda, Costes, Corinne, Rouaud, Olivier, Manckoundia, Patrick, Quipourt, Valérie, Marilier, Sophie, Franon, Evelyne, Bories, Lawrence, Pader, Marie-Laure, Basset, Marie-France, Lapoujade, Bruno, Faure, Valérie, Yung Tong, Michael Li, Malick-Loiseau, Christine, Cazaban-Campistron, Evelyne, Desclaux, Françoise, Blatge, Colette, Dantoine, Thierry, Laubarie-Mouret, Cécile, Saulnier, Isabelle, Clément, Jean-Pierre, Picat, Marie-Agnès, Bernard-Bourzeix, Laurence, Willebois, Stéphanie, Désormais, Iléana, Cardinaud, Noëlle, Bonnefoy, Marc, Livet, Pierre, Rebaudet, Pascale, Gédéon, Claire, Burdet, Catherine, Terracol, Flavien, Pesce, Alain, Roth, Stéphanie, Chaillou, Sylvie, Louchart, Sandrine, Sudres, Kristel, Lebrun, Nicolas, Barro-Belaygues, Nadège, Touchon, Jacques, Bennys, Karim, Gabelle, Audrey, Romano, Aurélia, Touati, Lynda, Marelli, Cécilia, Pays, Cécile, Robert, Philippe, Le Duff, Franck, Gervais, Claire, Gonfrier, Sébastien, Gasnier, Yannick, Bordes, Serge, Begorre, Danièle, Carpuat, Christian, Khales, Khaled, Lefebvre, Jean-François, El Idrissi, Samira Misbah, Skolil, Pierre, Salles, Jean-Pierre, Dufouil, Carole, Lehéricy, Stéphane, Chupin, Marie, Mangin, Jean-François, Bouhayia, Ali, Allard, Michèle, Ricolfi, Frédéric, Dubois, Dominique, Bonceour Martel, Marie Paule, Cotton, François, Bonafé, Alain, Chanalet, Stéphane, Hugon, Françoise, Bonneville, Fabrice, Cognard, Christophe, Chollet, François, Payoux, Pierre, Voisin, Thierry, Peiffer, Sophie, Hitzel, Anne, Zanca, Michel, Monteil, Jacques, Darcourt, Jacques, Molinier, Laurent, Derumeaux, Hélène, Costa, Nadège, Vincent, Christian, Perret, Bertrand, Vinel, Claire, Olivier-Abbal, Pascale, de Souto Barreto, Philipe, Goisser, Sabine, and Soriano, Gaëlle

Published
2018
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