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1. Association of APOE ε4 with cerebral gray matter volumes in non-demented older adults: The MEMENTO cohort study

Author

Mélina Régy, Aline Dugravot, Séverine Sabia, Aurore Fayosse, Jean-Francois Mangin, Marie Chupin, Clara Fischer, Vincent Bouteloup, Carole Dufouil, Geneviève Chêne, Claire Paquet, Bernard Hanseeuw, Archana Singh-Manoux, and Julien Dumurgier

Subjects
APOE genotype, MRI, Longitudinal analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Data on 2,045 non-demented individuals with memory complaints were drawn from the Memento cohort study to examine the association between Apolipoprotein E ε4 allele (APOE4) and regional brain gray matter volumes. Linear regression was used to examine the association of APOE4 and measures of regional gray matter volumes in cross-sectional analysis and change therein using longitudinal analyses based on two brain MRI performed at baseline and at two-year follow-up. Overall, in analyses adjusted for age, sex, and intracranial volume, the presence of APOE4 was associated with lower total gray matter volume at baseline and with a higher atrophy rate over the follow-up. The hippocampus and entorhinal cortex were the two gray matter regions most associated with APOE4. Further adjustment for cardiovascular risk factors had little impact on these associations. There was an interaction between age, APOE4 status and total brain volume atrophy rate, with evidence of an earlier age at onset of atrophy in hippocampal volume in APOE4 carriers compared to non-carriers. Those results are in accordance with the role of medial temporal structures in the greater risk of dementia observed in people carrying the APOE4 allele.

Published
2022
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2. Consensus-based guidance for conducting and reporting multi-analyst studies

Author

Balazs Aczel, Barnabas Szaszi, Gustav Nilsonne, Olmo R van den Akker, Casper J Albers, Marcel ALM van Assen, Jojanneke A Bastiaansen, Daniel Benjamin, Udo Boehm, Rotem Botvinik-Nezer, Laura F Bringmann, Niko A Busch, Emmanuel Caruyer, Andrea M Cataldo, Nelson Cowan, Andrew Delios, Noah NN van Dongen, Chris Donkin, Johnny B van Doorn, Anna Dreber, Gilles Dutilh, Gary F Egan, Morton Ann Gernsbacher, Rink Hoekstra, Sabine Hoffmann, Felix Holzmeister, Juergen Huber, Magnus Johannesson, Kai J Jonas, Alexander T Kindel, Michael Kirchler, Yoram K Kunkels, D Stephen Lindsay, Jean-Francois Mangin, Dora Matzke, Marcus R Munafò, Ben R Newell, Brian A Nosek, Russell A Poldrack, Don van Ravenzwaaij, Jörg Rieskamp, Matthew J Salganik, Alexandra Sarafoglou, Tom Schonberg, Martin Schweinsberg, David Shanks, Raphael Silberzahn, Daniel J Simons, Barbara A Spellman, Samuel St-Jean, Jeffrey J Starns, Eric Luis Uhlmann, Jelte Wicherts, and Eric-Jan Wagenmakers

Subjects
multi-analyst, metascience, statistical practice, science forum, expert consensus, analytical variability, Medicine, Science, Biology (General), QH301-705.5
Abstract

Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

Published
2021
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4. Neocortical morphometry in Huntington's disease: Indication of the coexistence of abnormal neurodevelopmental and neurodegenerative processes

Author

Jean-Francois Mangin, Denis Rivière, Edouard Duchesnay, Yann Cointepas, Véronique Gaura, Christophe Verny, Philippe Damier, Pierre Krystkowiak, Anne-Catherine Bachoud-Lévi, Philippe Hantraye, Philippe Remy, and Gwenaëlle Douaud

Subjects
Huntington's disease, MRI, Cortical morphometry, Sylvian fissure, Neurodevelopment, Asymmetry, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD. Here, we investigated cortical sulcal depth, related to degenerative process, as well as cortical sulcal length, related to developmental process, in early-stage HD and age-matched healthy controls. This morphometric analysis revealed significant differences in the HD participants compared with the healthy controls bilaterally in the central and intra-parietal sulcus, but also in the left intermediate frontal sulcus and calcarine fissure. As the primary visual cortex is not connected to the striatum, the latter result adds to the increasing in vivo evidence for primary cortical degeneration in HD. Those sulcal measures that differed between HD and healthy populations were mainly atrophy-related, showing shallower sulci in HD. Conversely, the sulcal morphometry also revealed a crucial difference in the imprint of the Sylvian fissure that could not be related to loss of grey matter volume: an absence of asymmetry in the length of this fissure in HD. Strong asymmetry in that cortical region is typically observed in healthy development. As the formation of the Sylvian fissure appears early in utero, and marked asymmetry is specifically found in this area of the neocortex in newborns, this novel finding likely indicates the foetal timing of a disease-specific, genetic interplay with neurodevelopment.

Published
2020
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5. Three-Dimensional Probabilistic Maps of Mesial Temporal Lobe Structures in Children and Adolescents’ Brains

Author

Antoine Bouyeure, David Germanaud, Dhaif Bekha, Victor Delattre, Julien Lefèvre, Charlotte Pinabiaux, Jean-Francois Mangin, Denis Rivière, Clara Fischer, Catherine Chiron, Lucie Hertz-Pannier, and Marion Noulhiane

Subjects
medial temporal lobe, probabilistic maps, development, hippocampus, parahippocampal gyrus, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Human anatomy, QM1-695
Abstract

The hippocampus and the adjacent perirhinal, entorhinal, temporopolar, and parahippocampal cortices are interconnected in a hierarchical MTL system crucial for memory processes. A probabilistic description of the anatomical location and spatial variability of MTL cortices in the child and adolescent brain would help to assess structure-function relationships. The rhinal sulcus (RS) and the collateral sulcus (CS) that border MTL cortices and influence their morphology have never been described in these populations. In this study, we identified the aforementioned structures on magnetic resonance images of 38 healthy subjects aged 7–17 years old. Relative to sulcal morphometry in the MTL, we showed RS-CS conformation is an additional factor of variability in the MTL that is not explained by other variables such as age, sex and brain volume; with an innovative method using permutation testing of the extrema of structures of interest, we showed that RS-SC conformation was not associated with differences of location of MTL sulci. Relative to probabilistic maps, we offered for the first time a systematic mapping of MTL structures in children and adolescent, mapping all the structures of the MTL system while taking sulcal morphology into account. Our results, with the probabilistic maps described here being freely available for download, will help to understand the anatomy of this region and help functional and clinical studies to accurately test structure-function hypotheses in the MTL during development.Free access to MTL pediatric atlas:http://neurovault.org/collections/2381/.

Published
2018
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6. An Example-Based Multi-Atlas Approach to Automatic Labeling of White Matter Tracts.

Author

Sang Wook Yoo, Pamela Guevara, Yong Jeong, Kwangsun Yoo, Joseph S Shin, Jean-Francois Mangin, and Joon-Kyung Seong

Subjects
Medicine, Science
Abstract

We present an example-based multi-atlas approach for classifying white matter (WM) tracts into anatomic bundles. Our approach exploits expert-provided example data to automatically classify the WM tracts of a subject. Multiple atlases are constructed to model the example data from multiple subjects in order to reflect the individual variability of bundle shapes and trajectories over subjects. For each example subject, an atlas is maintained to allow the example data of a subject to be added or deleted flexibly. A voting scheme is proposed to facilitate the multi-atlas exploitation of example data. For conceptual simplicity, we adopt the same metrics in both example data construction and WM tract labeling. Due to the huge number of WM tracts in a subject, it is time-consuming to label each WM tract individually. Thus, the WM tracts are grouped according to their shape similarity, and WM tracts within each group are labeled simultaneously. To further enhance the computational efficiency, we implemented our approach on the graphics processing unit (GPU). Through nested cross-validation we demonstrated that our approach yielded high classification performance. The average sensitivities for bundles in the left and right hemispheres were 89.5% and 91.0%, respectively, and their average false discovery rates were 14.9% and 14.2%, respectively.

Published
2015
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7. Diabetes mellitus and cognition: A pathway analysis in the MEMENTO cohort

Author

Eric, Frison, Cecile, Proust-Lima, Jean-Francois, Mangin, Marie-Odile, Habert, Stephanie, Bombois, Pierre-Jean, Ousset, Florence, Pasquier, Olivier, Hanon, Claire, Paquet, Audrey, Gabelle, Mathieu, Ceccaldi, Cédric, Annweiler, Pierre, Krolak-Salmon, Yannick, Béjot, Catherine, Belin, David, Wallon, Mathilde, Sauvee, Emilie, Beaufils, Isabelle, Bourdel-Marchasson, Isabelle, Jalenques, Marie, Chupin, Geneviève, Chêne, Carole, Dufouil, Jean, Zinszner, 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), CATI Multicenter Neuroimaging Platform (CATI), IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Groupe hospitalier Broca, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), University of Western Ontario (UWO), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hopital Saint-Louis [AP-HP] (AP-HP), 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), Centre Mémoire de Ressources et de Recherche [Grenoble] (CMRR), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), 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), Support within the 'Investissement d'Avenir' (ANR-10-AIHU-06) program., Gestionnaire, Hal Sorbonne Université, Service de Médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine nucléaire [CHU Pitié-Salpétrière], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, [SDV]Life Sciences [q-bio], Comorbidity, Neuropsychological Tests, Cohort Studies, Alzheimer Disease, Diabetes Mellitus, Humans, Cognitive Dysfunction, Aged, Aged, 80 and over, Amyloid beta-Peptides, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Cerebral Small Vessel Diseases, Positron-Emission Tomography, Nerve Degeneration, Female, France, Biomarkers, Research Article
Abstract

International audience; Objective: To assess the role of biomarkers of Alzheimer's Disease (AD), neurodegeneration and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition.Methods: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent or self-report. We used structural equation modelling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ42/Aβ40 ratio and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (five neuropsychological tests), adjusting for potential confounders.Results: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089; -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning.Conclusion: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.

Published
2021
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8. A study of feasibility for genome-wide haplotype association of complex traits in imaging genetics

Author

Jean-Francois Mangin, Edith Le Floch, Morgane Pierre-Jean, Vincent Frouin, Slim Karkar, Cathy Philippe, Claire Dandine-Roulland, Yann Le Guen, Unité Analyse et Traitement de l'Information (UNATI), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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, and Centre National de Recherche en Génomique Humaine (CNRGH)

Subjects
[SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Imaging genetics, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 05 social sciences, Haplotype, Computational biology, Biology, Sulcus, Biobank, Genome, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neuroimaging, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], medicine, 0501 psychology and cognitive sciences, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Association (psychology), Chromosome 21, 030217 neurology & neurosurgery
Abstract

International audience; Imaging-genetics cohorts allow to find associations between genotyped variants and brain imaging features. They are invaluable tools to evaluate the part of genetics and environment in the brain characteristic variance observed in normal and pathological populations. The present analyses were conducted using the 2018 UK Biobank (UKB) data release, and included 15,040 subjects for which sulcal opening, a measure of sulcus width, are extracted for 126 sulci using BrainVisa/Morphologist pipeline. Based on genetic maps, continuous blocks of high-confidence phase are extracted using the haplotype dataset of UK Biobank. The feasibility study analyzes 13,942 haplotypes of 1,756 blocks on chromosome 21, obtained with a stringent block definition, and shows that block-based test seems underpowered compared to haplotype-based association test.

Published
2018

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