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

Author: Frederic Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro de Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Sandrine Harston, Anne Botzung, Timothée Albasser, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Stéphane Kremer, Olivier Bousiges, Marc Verny, Candice Muller, Nathalie Philippi, Geneviève Chene, Benjamin Cretin, Jean-François Mangin, and Carole Dufouil
Subjects: Dementia with Lewy bodies, Prodromal, Mild cognitive impairment, Subjective cognitive impairment, Lewy body disease, Mild neurocognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT01926249
Published: 2022
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2. Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author: Leslie Grasset, Cécile Proust-Lima, Jean-François Mangin, Marie-Odile Habert, Bruno Dubois, Claire Paquet, Olivier Hanon, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Renaud David, Therese Jonveaux, Catherine Belin, Adrien Julian, Isabelle Rouch-Leroyer, Jérémie Pariente, Maxime Locatelli, Marie Chupin, Geneviève Chêne, Carole Dufouil, and on behalf of the Memento Cohort Study group
Subjects: Social factors, Lifestyle factors, Cognitive function, Brain markers, Pathology, Pathways, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer’s disease and related dementia (ADRD), and cognition. Methods The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. Results Participants’ mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β = − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD. Conclusions Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.
Published: 2022
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3. Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Author: Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Jacques Hugon, Olivier Hanon, Jean-François Dartigues, Sandrine Harston, Audrey Gabelle, Mathieu Ceccaldi, Olivier Beauchet, Pierre Krolak-Salmon, Renaud David, Olivier Rouaud, Olivier Godefroy, Catherine Belin, Isabelle Rouch, Nicolas Auguste, David Wallon, Athanase Benetos, Jérémie Pariente, Marc Paccalin, Olivier Moreaud, Caroline Hommet, François Sellal, Claire Boutoleau-Bretonniére, Isabelle Jalenques, Armelle Gentric, Pierre Vandel, Chabha Azouani, Ludovic Fillon, Clara Fischer, Helen Savarieau, Gregory Operto, Hugo Bertin, Marie Chupin, Vincent Bouteloup, Marie-Odile Habert, Jean-François Mangin, Geneviève Chêne, and on behalf of the MEMENTO cohort Study Group
Subjects: Alzheimer’s disease, Cognitive aging, Cohort studies, Natural history studies (prognosis), Neuroimaging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The natural history and disease mechanisms of Alzheimer’s disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. Methods In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR]
Published: 2017
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4. The need for harmonisation and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group

Author: Alberto Costa, Thomas Bak, Paolo Caffarra, Carlo Caltagirone, Mathieu Ceccaldi, Fabienne Collette, Sebastian Crutch, Sergio Della Sala, Jean François Démonet, Bruno Dubois, Emrah Duzel, Peter Nestor, Sokratis G. Papageorgiou, Eric Salmon, Sietske Sikkes, Pietro Tiraboschi, Wiesje M. van der Flier, Pieter Jelle Visser, and Stefano F. Cappa
Subjects: Neurodegenerative dementia, Cognitive assessment, Behavioural assessment, Neuropsychological tests, Longitudinal studies, European research, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status. Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a “big data” common data set. We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe. A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries.
Published: 2017
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5. Un trouble à symptomatologie neurologique fonctionnelle dans le contexte de la pandémie de la Covid-19

Author: Lucas Ronat, Stéphan Grimaldi, Léa Corneille, Eric Guedj, and Mathieu Ceccaldi
Subjects: Behavioral Neuroscience, Neuropsychology and Physiological Psychology, Cognitive Neuroscience
Published: 2022
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6. Semantic loss marks early Alzheimer's disease‐related neurodegeneration in older adults without dementia

Author: Jet M. J. Vonk, Vincent Bouteloup, Jean‐François Mangin, Bruno Dubois, Frédéric Blanc, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Pierre Krolak‐Salmon, Catherine Belin, Thérèse Rivasseau‐Jonveaux, Adrien Julian, François Sellal, Eloi Magnin, Marie Chupin, Marie‐Odile Habert, Geneviève Chêne, Carole Dufouil, and and on behalf of the MEMENTO cohort Study Group
Subjects: Alzheimer's disease, amnestic, biomarkers, category fluency, cognitive aging, cohort studies, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Objective To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)‐specific neurodegeneration using longitudinal multimodal neuroimaging measures. Methods Change in verbal fluency was analyzed among 2261 non‐demented individuals with a follow‐up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non‐amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow‐up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F‐fluorodeoxyglucose brain positron emission tomography (18F‐FDG‐PET) imaging (n = 756) using linear regression models across 2 years of follow‐up. Results Semantic fluency declined—fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)—while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F‐FDG‐PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus–posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole‐brain neurodegeneration over time was associated with faster decline in both fluencies, while AD‐specific regions were associated with a faster rate of decline in semantic but not letter fluency. Interpretation This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD‐specific neurodegeneration.
Published: 2020
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7. Primary progressive aphasias associated with C9orf72 expansions: Another side of the story

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

Author: Jacques-Yves Campion, Eric Guedj, Tatiana Horowitz, Mathieu Ceccaldi, Fanny Barthelemy, Serge Cammilleri, Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Otten, Lisa
Subjects: Male, deconditioning, Emotions, Physiology, SARS‐CoV‐2, lockdown, Deconditioning, Cortex (anatomy), Longitudinal Studies, Social isolation, FDG-PET, long COVID, Research Articles, Aged, 80 and over, Radiological and Ultrasound Technology, Motor Cortex, Brain, Cognition, Middle Aged, medicine.anatomical_structure, Social Isolation, Neurology, Quarantine, Female, Anatomy, medicine.symptom, Research Article, deconfinement, FDG‐PET, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Context (language use), pyramidal tract, Post-Acute COVID-19 Syndrome, COVID‐19, Fluorodeoxyglucose F18, medicine, Humans, Radiology, Nuclear Medicine and imaging, Exercise, Pandemics, Aged, Retrospective Studies, Pyramidal tracts, SARS-CoV-2, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, physical activities, COVID-19, Somatosensory Cortex, brain metabolism, Positron-Emission Tomography, Neurology (clinical), Nerve Net, Radiopharmaceuticals, business
Abstract: This study aims to evaluate the impact of French national lockdown of 55 days on brain metabolism of patients with neurological disorders. Whole‐brain voxel‐based PET analysis was used to correlate 18F‐FDG metabolism to the number of days after March 17, 2020 (in 95 patients; mean age: 54.3 years ± 15.7; 59 men), in comparison to the same period in 2019 before the SARS‐CoV‐2 outbreak (in 212 patients; mean age: 59.5 years ± 15.8; 114 men), and to the first 55 days of deconfinement (in 188 patients; mean age: 57.5 years ± 16.5; 93 men). Lockdown duration was negatively correlated to the metabolism of the sensory‐motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap was found with the reported pattern of hypometabolism in long COVID (, Lockdown duration is negatively correlated to the metabolism of the sensory‐motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap is found with the reported pattern of hypometabolism in long COVID (
Published: 2021
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9. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

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

Author: Jérémie, Lespinasse, Geneviève, Chêne, Jean-Francois, Mangin, Bruno, Dubois, Frederic, Blanc, Claire, Paquet, Olivier, Hanon, Vincent, Planche, Audrey, Gabelle, Mathieu, Ceccaldi, Cedric, Annweiler, Pierre, Krolak-Salmon, Olivier, Godefroy, David, Wallon, Mathilde, Sauvée, Sébastien, Bergeret, Marie, Chupin, Cécile, Proust-Lima, Carole, Dufouil, Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lariboisière-François Widal, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Bordeaux (UB), Centre Mémoire de Ressources et de Recherches [Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM), U708, Neuroepidemiology, Paris, France
Subjects: cognition, hypertension, Epidemiology, Health Policy, structural equation model, amyloid beta 42, hippocampal volume, cortical thickness, white matter hyperintensities, fluorodeoxyglucose positron emission tomography, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, mediation, tau, Neurology (clinical), Geriatrics and Gerontology, positron emission tomography amyloid, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood.Methods: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data.Results: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers.Discussion: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association.Highlights: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.
Published: 2022
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11. Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

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

Author: Natalina Gour, Jean-Philippe Ranjeva, Mathieu Ceccaldi, Sylviane Confort-Gouny, Emmanuel J. Barbeau, Elisabeth Soulier, Maxime Guye, Mira Didic, and Olivier Felician
Published: 2011
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13. Biomarker counseling, disclosure of diagnosis and follow‐up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey

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

Author: Frederic Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Sandrine Harston, Anne Botzung, Timothée Albasser, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Stéphane Kremer, Olivier Bousiges, Marc Verny, Candice Muller, Nathalie Philippi, Geneviève Chene, Benjamin Cretin, Jean-François Mangin, and Carole Dufouil
Subjects: nervous system, mental disorders, behavioral disciplines and activities, nervous system diseases
Abstract: Background: Isolated subjective cognitive impairment (SCI) and mild neurocognitive impairment (MCI) are prodromal phase of dementia with Lewy bodies (DLB). Memento is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods: Participants of the French Memento cohort study recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB group (pro-DLB) was done using a two-criteria cut-off score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group), and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET and amyloid PET were done.Results: The Pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia. The Pro-DLB group had isolated lower P-Tau and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected). Conclusions: Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. Biomarkers confirmed the non-Alzheimer profile. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients.Trial registration: Clinicaltrials.gov, NCT01926249 .
Published: 2022
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15. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

Author: Sven Joubert, Olivier Felician, Emmanuel J. Barbeau, Mira Didic, Michel Poncet, and Mathieu Ceccaldi
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment). The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.
Published: 2008
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16. Telemedicine in French memory clinics during Covid‐19 crisis

Author: Alexandre Morin, Thibault Pressat‐Laffouilhere, Marie Sarazin, Julien Lagarde, Carole Roue‐Jagot, Claire Paquet, Emmanuel Cognat, Julien Dumurgier, Florence Pasquier, Thibaud Lebouvier, Mathieu Ceccaldi, Olivier Godefroy, Olivier Martinaud, Julien Grosjean, Aline Zarea, David Maltête, and David Wallon
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021
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17. SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration

Author: Barbier, Mathieu, Camuzat, Agnès, Hachimi, Khalid El, Guegan, Justine, Rinaldi, Daisy, Lattante, Serena, Houot, Marion, Sánchez-Valle, Raquel, Sabatelli, Mario, Antonell, Anna, Molina-Porcel, Laura, Clot, Fabienne, Couratier, Philippe, van der Ende, Emma, van der Zee, Julie, Manzoni, Claudia, Camu, William, Cazeneuve, Cécile, Sellal, François, Didic, Mira, Golfier, Véronique, Pasquier, Florence, Duyckaerts, Charles, Rossi, Giacomina, Bruni, Amalia C, Alvarez, Victoria, Gómez-Tortosa, Estrella, de Mendonça, Alexandre, Graff, Caroline, Masellis, Mario, Nacmias, Benedetta, Oumoussa, Badreddine Mohand, Jornea, Ludmila, Forlani, Sylvie, Van Deerlin, Viviana, Rohrer, Jonathan D, Gelpi, Ellen, Rademakers, Rosa, Van Swieten, John, Le Guern, Eric, Van Broeckhoven, Christine, Ferrari, Raffaele, Génin, Emmanuelle, Brice, Alexis, Ber, Le, Isabelle Alexis Brice, Sophie, Auriacombe, Serge, Belliard, Anne, Bertrand, Anne, Bissery, Fre ́ de, ́ ric Blanc, Marie-Paule, Boncoeur, Ste, ́ phanie Bombois, Claire Boutoleau-Bretonnie` re, Agne`, s Camuzat, Mathieu, Ceccaldi, Marie, Chupin, Philippe, Couratier, Olivier, Colliot, Vincent, Deramecourt, Mira, Didic, Bruno, Dubois, Charles, Duyckaerts, Fre ́ de, ́ rique Etcharry-Bouyx, Aure, ́ lie Guignebert-Funkiewiez, Maı ̈te, ́ Formaglio, ́ ronique Golfier, Ve, Marie-Odile, Habert, Didier, Hannequin, Lucette, Lacomblez, Julien, Lagarde, ́ raldine Lautrette, Ge, Isabelle Le Ber, Benjamin Le Toullec, Richard, Levy, Marie-Anne, Mackowiak, Bernard-Franc ̧ois Michel, Florence, Pasquier, Thibaud, Lebouvier, Carole Roue, ́ -Jagot, Christel Thauvin- Robinet, Catherine, Thomas-Anterion, Je ́ re, ́ mie Pariente, Franc ̧ois Salachas, Sabrina, Sayah, Franc ̧ois Sellal, Assi-Herve, ́ Oya, Daisy, Rinaldi, Adeline, Rollin-Sillaire, Martine, Vercelletto, David, Wallon, Armelle, Rametti-Lacroux, Raffaele, Ferrari, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Adaikalavan, Ramasamy, Kwok, John B. J., Carol Dobson- Stone, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Olivier, Piguet, Lauren, Bartley, Elizabeth, Thompson, Isabel Herna, ́ ndez, Agustı ́n Ruiz, Merce`, Boada, Barbara, Borroni, Alessandro, Padovani, Carlos, Cruchaga, Cairns, Nigel J., Luisa, Benussi, Giuliano, Binetti, Roberta, Ghidoni, Gianluigi, Forloni, Diego, Albani, Daniela, Galimberti, Chiara, Fenoglio, Maria, Serpente, Elio, Scarpini, ́ n, Jordi Clarimo, Alberto Lleo, ́, Rafael, Blesa, Maria Landqvist Waldo, ̈, Karin, Nilsson, Christer, Nilsson, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Jordan, Grafman, Morris, Christopher M., Johannes, Attems, Griffiths, Timothy D., Mckeith, Ian G., Thomas, Alan J., Pietro, Pietrini, Edward, Uey, Wassermann, Eric M., Atik, Baborie, Evelyn, Jaros, Tierney, Michael C., Pau, Pastor, Cristina, Razquin, Sara, Ortega-Cubero, Elena, Alonso, Robert, Perneczky, Janine, Diehl-Schmid, Panagiotis, Alexopoulos, Alexander, Kurz, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Ekaterina, Rogaeva, Peter St George-Hyslop, Giacomina, Rossi, Fabrizio, Tagliavini, Giorgio, Giaccone, Rowe, James B., Schlachetzki, Johannes C. M., James, Uphill, John, Collinge, Simon, Mead, Adrian, Danek, Van Deerlin, Vivianna M., Murray, Grossman, Trojanowski, John Q., Julie van der Zee, Christine Van Broeckhoven, Cappa, Stefano F., Isabelle, Leber, Alexis, Brice, Benedetta, Nacmias, Sandro, Sorbi, Silvia, Bagnoli, Irene, Piaceri, Nielsen, Jørgen E., Hjermind, Lena E., Matthias, Riemenschneider, Manuel, Mayhaus, Bernd, Ibach, Gilles, Gasparoni, Sabrina, Pichler, Wei, Gu, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Maria Grazia Spillantini, Morris, Huw R., Patrizia, Rizzu, Peter, Heutink, Snowden, Julie S., Sara, Rollinson, Anna, Richardson, Alexander, Gerhard, Bruni, Amalia C., Raffaele, Maletta, Francesca, Frangipane, Chiara, Cupidi, Livia, Bernardi, Maria, Anfossi, Maura, Gallo, Maria Elena Conidi, Nicoletta, Smirne, Rosa, Rademakers, Matt, Baker, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., David, Knopman, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Howard, Rosen, van Swieten, John C., Dopper, Elise G. P., Harro, Seelaar, Pijnenburg, Yolande A. L., Philip, Scheltens, Giancarlo, Logroscino, Rosa, Capozzo, Valeria, Novelli, Puca, Annibale A., Massimo, Franceschi, Alfredo, Postiglione, Graziella, Milan, Paolo, Sorrentino, Mark, Kristiansen, Huei-Hsin, Chiang, Caroline, Graff, Adeline, Rollin, Dimitrios, Kapogiannis, Luigi, Ferrucci, Stuart, Pickering-Brown, Singleton, Andrew B., John, Hardy, Parastoo, Momeni., Neurology, Amsterdam Neuroscience - Neurodegeneration, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Dupuytren [CHU Limoges], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Molecular Neurology (VIB-UAntwerp), University of Antwerp (UA), University College of London [London] (UCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Yves le Foll, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Hospital Central de Asturias, Institute of Health Research of Principado de Asturias (ISPA), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Karolinska University Hospital [Stockholm], Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione Don Carlo Gnocchi, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), The French clinical and genetic Research network on FTLD/FTLD-ALS and PREVDEMALS, The International Frontotemporal Dementia Genomics Consortium, The European Early Onset Dementia (EU -EOD) Consortium, Brainbank Neuro-CEB Neuropathology Network, and Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS
Subjects: Adult, Male, TDP-43, C9orf72, SLITRK2, amyotrophic lateral sclerosis, frontotemporal dementia, Nerve Tissue Proteins, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Cohort Studies, Genes, X-Linked, 80 and over, Medicine, Dementia, Humans, Allele, Age of Onset, Polymorphism, Aged, Aged, 80 and over, biology, C9orf72 Protein, business.industry, Membrane Proteins, MESH: Frontotemporal Lobar Degeneration / epidemiology, Frontotemporal Lobar, Degeneration / genetics, Genes, X-Linked / genetics, Genome-Wide Association Study / methods, Frontotemporal lobar degeneration, Single Nucleotide, Middle Aged, X-Linked, medicine.disease, Amyotrophic lateral sclerosis, Minor allele frequency, Genes, Immunology, Synaptophysin, biology.protein, Female, MESH: Adult, C9orf72 Protein / genetics, Frontotemporal Lobar Degeneration / diagnosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Human medicine, Neurology (clinical), MESH: Humans, Membrane Proteins / genetics, Nerve Tissue Proteins / genetics, Polymorphism, Single Nucleotide / genetics, Age of onset, Frontotemporal Lobar Degeneration, business, Frontotemporal dementia, Genome-Wide Association Study
Abstract: The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.
Published: 2021
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18. Maladies d’Alzheimer et apparentées : oui, ce sont bien des « maladies » !

Author: Mathieu Ceccaldi
Published: 2022
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19. 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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20. Long COVID and the brain network of Proust's madeleine: targeting the olfactory pathway

Author: Eric Guedj, Carole Eldin, Aurélie Kas, Thomas Radulesco, Mathieu Ceccaldi, Silvia Morbelli, Françoise Lazarini, Dominique Salmon-Ceron, Charlotte Hautefort, Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Service Central de Biophysique et Médecine Nucléaire, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Oto-rhino-laryngologie et Chirurgie cervico-faciale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Hôtel-Dieu [Paris], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: 0301 basic medicine, Olfactory system, [SDV]Life Sciences [q-bio], Olfaction Disorders, 0302 clinical medicine, Severe acute respiratory syndrome coronavirus 2, Medicine, 030212 general & internal medicine, (18)F-FDG, Complaints, Brain network, Coronavirus disease 2019, Rehabilitation, General Medicine, Olfactory Bulb, Anosmia, Emotion, Memory, Olfaction, Positron emission tomography, [, 18, F]fluorodeoxyglucose, COVID-19, Fluorodeoxyglucose F18, Humans, Memory Disorders, Positron-Emission Tomography, Radiopharmaceuticals, Infectious Diseases, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Microbiology (medical), 2019-20 coronavirus outbreak, 030106 microbiology, Stress, 03 medical and health sciences, Functional brain, Post-Acute COVID-19 Syndrome, In patient, [18F]fluorodeoxyglucose, business.industry, SARS-CoV-2, Olfactory bulb, PET, Commentary, business, Neuroscience
Abstract: International audience; We detail in this Commentary our hypothesis of functional brain dysfunction in patients with long Covid in relation with the impairment of olfactory pathways, and discuss possible implications for the therapeutic management of these patients.
Published: 2021
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21. From early limbic inflammation to long COVID sequelae

Author: Eric Guedj, Serge Cammilleri, Elsa Kaphan, Mathieu Ceccaldi, Silvia Morbelli, Flavio Nobili, Pierre Dudouet, Carole Eldin, Jacques-Yves Campion, Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vecteurs - Infections tropicales et méditerranéennes (VITROME), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: Inflammation, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], COVID-19, Post-Acute COVID-19 Syndrome, Immunology, Disease Progression, Medicine, Humans, Neurology (clinical), medicine.symptom, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021
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22. Investigating the association between cancer and the risk of dementia: Results from the Memento cohort

Author: Mathieu Ceccaldi, Audrey Gabelle, Bruno Dubois, Carole Dufouil, David Wallon, Olivier Hanon, Armelle Gentric, Pierre Krolak-Salmon, Yannick Béjot, Geneviève Chêne, Olivier Godefroy, Jonviea D Chamberlain, Anaïs Rouanet, Florence Pasquier, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Mémoire de Ressources et de Recherches (CMRR), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Bordeaux [Bordeaux], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, medicine.medical_specialty, media_common.quotation_subject, Neuropsychological Tests, illness-death model, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, illness‐death model, 0302 clinical medicine, Developmental Neuroscience, Internal medicine, Neoplasms, Epidemiology, medicine, Dementia, Humans, cancer, Cognitive Dysfunction, selection bias, 030212 general & internal medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mortality, Research Articles, media_common, Aged, Selection bias, business.industry, Health Policy, Hazard ratio, Cancer, Cognition, Alzheimer's disease, medicine.disease, Confidence interval, 3. Good health, Psychiatry and Mental health, Cohort, Female, epidemiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), France, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research Article, dementia
Abstract: International audience; IntroductionStudies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding.MethodsThis study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness‐death models (IDMs) were used to estimate transition‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry.ResultsThe analytical sample (N = 2258) excluded 65 individuals without follow‐up information. At the end of follow‐up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35‐0.97), with a corresponding E‐value of 2.84 (lower CI = 1.21).DiscussionThis study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.
Published: 2021
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23. 18F-FDG brain PET hypometabolism in patients with long COVID

Author: Paul Habert, Didier Raoult, Hervé Tissot-Dupont, Eric Guedj, F. Barthelemy, Matthieu Million, Jacques-Yves Campion, Mathieu Ceccaldi, Serge Cammilleri, Elsa Kaphan, S. Guis, Fabienne Brégeon, Pierre Dudouet, Carole Eldin, Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service de Neurologie, Hôpital de la Timone, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Interventionnelle Expérimentale (LIIE), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Hippocampus, Paralimbic cortex, Gastroenterology, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Hyposmia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Fatigue, ComputingMilieux_MISCELLANEOUS, Complaints, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Brain, General Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Nasal decongestant, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, medicine.medical_specialty, Long COVID, Anosmia, Orbital gyri, Context (language use), Stress, 03 medical and health sciences, Post-Acute COVID-19 Syndrome, Angiotensin-converting enzyme, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Memory, Fluorodeoxyglucose F18, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Olfactory Region, SARS-CoV-2, business.industry, COVID-19, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Dysautonomia, 18F-FDG, PET, Positron-Emission Tomography, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: Purpose In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as “long COVID.” We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. Methods PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients’ characteristics and functional complaints. Results In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel
Published: 2021
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24. Pathways involved in the relationship between resilience and cognitive function: The Memento cohort

Author: Geneviève Chêne, Pierre Krolak Salmon, Claire Paquet, Audrey Gabelle, Florence Pasquier, Leslie Grasset, Frédéric Blanc, Cédric Annweiler, Olivier Hanon, Mathieu Ceccaldi, Carole Dufouil, Bruno Vellas, and Bruno Dubois
Subjects: Gerontology, medicine.medical_specialty, Epidemiology, Health Policy, Cognition, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, medicine, Neurology (clinical), Geriatrics and Gerontology, Resilience (network), Psychology
Published: 2020
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25. Biomarker counseling, disclosure of diagnosis, and follow‐up in patients with mild cognitive impairment: A European survey of EADC centers

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

Author: Anne Botzung, Izzie Jacques Namer, Carole Dufouil, Frédéric Blanc, Jean-François Dartigues, Catherine Martin-Hunyadi, Jean-François Mangin, Marie Chupin, Clara Fischer, Marie-Odile Habert, Paulo Loureiro de Sousa, Claire Paquet, Vincent Bouteloup, Mathieu Ceccaldi, Nathalie Philippi, Pierre Krolak Salmon, Florence Pasquier, Renaud David, David Wallon, Geneviève Chêne, Catherine Demuynck, Olivier Bousiges, Stéphane Kremer, Catherine Belin, Timothée Albasser, Olivier Moreaud, Mathilde Sauvée, Benjamin Cretin, and Audrey Gabelle
Subjects: medicine.medical_specialty, Epidemiology, Dementia with Lewy bodies, Behavioral neurology, business.industry, Health Policy, Prodromal Stage, Neuropsychiatry, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Longitudinal cohort, Psychiatry, business
Published: 2020
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27. Progressive phonagnosia in a telephone operator carrying a C9orf72 expansion

Author: Mira Didic, Lucas Ronat, Mathieu Ceccaldi, Olivier Felician, Isabelle Le Ber, Pascal Belin, Eve Tramoni-Negre, Virginia Aglieri, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Otten, Lisa
Subjects: 2019-20 coronavirus outbreak, Cognitive Neuroscience, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Experimental and Cognitive Psychology, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, C9orf72, Network level, medicine, Humans, Dementia, 0501 psychology and cognitive sciences, ComputingMilieux_MISCELLANEOUS, C9orf72 Protein, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Phonagnosia, Operator (linguistics), [SCCO.NEUR] Cognitive science/Neuroscience, Neurodegenerative Diseases, Recognition, Psychology, medicine.disease, Telephone, Phenotype, Neuropsychology and Physiological Psychology, Frontotemporal Dementia, Psychology, Neuroscience, 030217 neurology & neurosurgery, Professional expertise
Abstract: Selectivity is the rule, rather than the exception, in neurodegenerative disease. A retired telephone operator carrying a C9orf72 expansion developed phonagnosia, a selective impairment of voice recognition, contrasting with intact person knowledge and recognition of faces, as a presenting sign of genetically confirmed fronto-temporal dementia. Since the dysfunction in this patient fell into his area of professional expertise, we discuss if overload in voice related neural networks might have caused failure propagating to connected nodes. The interaction with downstream molecular events, triggered by the C9orf72 expansion, may have led to breakdown at the network level, leading to this specific phenotype.
Published: 2020
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28. Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers

Author: Alexandre Eusebio, Olivier Felician, Agnès Benvenutto, Eric Guedj, Lejla Koric, Jean-Philippe Azulay, Mathieu Ceccaldi, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Centre Mémoire de Ressources et de Recherche, CHU Marseille, Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: 0301 basic medicine, Male, Pathology, Eye Movements, 0302 clinical medicine, Cerebrospinal fluid, Cognition, ComputingMilieux_MISCELLANEOUS, Dystonia, Cerebral Cortex, Movement Disorders, biology, General Neuroscience, Parkinsonism, Amyloidosis, Dopaminergic, General Medicine, Syndrome, Middle Aged, Mental Status and Dementia Tests, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Female, inorganic chemicals, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Amyloid, 03 medical and health sciences, Alzheimer Disease, Spect imaging, medicine, Saccades, Humans, Dopamine transporter, Aged, Tomography, Emission-Computed, Single-Photon, Dopamine Plasma Membrane Transport Proteins, business.industry, organic chemicals, nutritional and metabolic diseases, medicine.disease, 030104 developmental biology, Positron-Emission Tomography, biology.protein, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers, Psychomotor Performance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Brain Stem
Abstract: Corticobasal syndrome (CBS) is a neuropathologically heterogeneous entity. The use of cerebrospinal fluid and amyloid biomarkers enables detection of underlying Alzheimer's disease (AD) pathology. We thus compared clinical, eye movement, and 18FDG-PET imaging characteristics in CBS in two groups of patients divided according to their amyloid biomarkers profile. Fourteen patients presenting with CBS and amyloidosis (CBS-A+) were compared with 16 CBS patients without amyloidosis (CBS-A-). The two groups showed similar motor abnormalities (parkinsonism, dystonia) and global cognitive functions. Unlike CBS-A+ patients who displayed more posterior cortical abnormalities, CBS-A- patients demonstrated more anterior cortical and brain stem dysfunctions on the basis of neuropsychological testing, study of saccade velocities and brain hypometabolism areas on 18FDG-PET. Interestingly, Dopamine Transporter SPECT imaging showed similar levels of dopaminergic degeneration in both groups. These findings confirm common and distinct brain abnormalities between the different neurodegenerative diseases that result in CBS. We demonstrate the importance of a multidisciplinary approach to improve diagnosis in vivo in particular on oculomotor examination.
Published: 2020
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29. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease

Author: Anne-Laure Aziz, Jean-Philippe Ranjeva, Eric Guedj, José Boucraut, Lejla Koric, Lauréline Duprat, Olivier Felician, Sven Joubert, Bernard Giusiano, Mathieu Ceccaldi, Mira Didic, Claude Gueriot, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche de l'Institut universitaire de gériatrie, Université de Montréal (UdeM), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre de Mémoire de Ressources et de Recherche [Hôpital La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE)-CHU Marseille, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Mémoire de Ressources et de Recherche, CHU Marseille, and Guedj, Eric
Subjects: Male, 0301 basic medicine, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Disease, Neuroimaging biomarkers, Severity of Illness Index, Cognition, 0302 clinical medicine, Semantic memory, Early-onset Alzheimer's disease, Age of Onset, Aged, 80 and over, General Neuroscience, Neurodegeneration, Brain, Middle Aged, Alzheimer's disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Amyloid, medicine.medical_specialty, Temporoparietal junction, Neuroimaging, 03 medical and health sciences, Atrophy, Alzheimer Disease, Memory, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], snc, Positron emission tomography imaging, Aged, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Glucose, 030104 developmental biology, Positron-Emission Tomography, Posterior cingulate, Nerve Degeneration, Neurology (clinical), Geriatrics and Gerontology, Age of onset, Neuroscience, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.
Published: 2017
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30. Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia

Author: Cédric Annweiler, Marie-Odile Habert, Audrey Gabelle, François Sellal, Geneviève Chêne, Vincent Bouteloup, Frédéric Blanc, Eloi Magnin, Jet M.J. Vonk, Catherine Belin, Carole Dufouil, Adrien Julian, Marie Chupin, Jean-François Mangin, Bruno Dubois, Pierre Krolak-Salmon, Mathieu Ceccaldi, Thérèse Rivasseau-Jonveaux, Admin, Oskar, Columbia University [New York], University Medical Center [Utrecht], 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), CHU Bordeaux [Bordeaux], 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), CATI Multicenter Neuroimaging Platform (CATI), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), 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), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centres Mémoire de Ressources et de Recherche Montpellier (CMRR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], 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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Mémoire de Ressources et de Recherche [CHRU de Besançon] (CMRR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques [CHRU de Besançon], Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO)
Subjects: medicine.medical_specialty, Clinical Dementia Rating, Audiology, lcsh:Geriatrics, lcsh:RC346-429, 03 medical and health sciences, Fluency, 0302 clinical medicine, Neuroimaging, cohort studies, medicine, Brain positron emission tomography, MORPH3Eus, Dementia, Verbal fluency test, Cognitive decline, 10. No inequality, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, 0303 health sciences, neuroimaging, amnestic, business.industry, cognitive aging, semantic fluency, verbal fluency, biomarkers, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, letter fluency, Alzheimer's disease, medicine.disease, Hyperintensity, MCI, Psychiatry and Mental health, lcsh:RC952-954.6, VINTAGE, Cognitive & Behavioral Assessment, Neurology (clinical), category fluency, business, Alzheimer’s disease, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Research Article
Abstract: International audience; Objective: To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)‐specific neurodegeneration using longitudinal multimodal neuroimaging measures.Methods: Change in verbal fluency was analyzed among 2261 non‐demented individuals with a follow‐up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non‐amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow‐up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F‐fluorodeoxyglucose brain positron emission tomography (18F‐FDG‐PET) imaging (n = 756) using linear regression models across 2 years of follow‐up.Results: Semantic fluency declined—fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)—while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F‐FDG‐PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus–posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole‐brain neurodegeneration over time was associated with faster decline in both fluencies, while AD‐specific regions were associated with a faster rate of decline in semantic but not letter fluency.Interpretation: This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD‐specific neurodegeneration.
Published: 2020
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31. Neurobiol Aging

Author: Pascaline Cassagnaud, David Wallon, Vincent Deramecourt, Florence Pasquier, Didier Hannequin, NeuroCEB Brain Bank, Thibaud Lebouvier, Sophie Auriacombe, Bruno Dubois, Mathieu Ceccaldi, Claude-Alain Maurage, Isabelle Le Ber, Marie Sarazin, Florence Lebert, Maxime Bertoux, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Aging, Pathology, medicine.medical_specialty, Amnesia, Autopsy, Disease, Neuropsychological Tests, SEPIA, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Memory, Predictive Value of Tests, medicine, Humans, Dementia, Cognitive decline, Pathological, Aged, Cued speech, Verbal Behavior, business.industry, General Neuroscience, Middle Aged, medicine.disease, 030104 developmental biology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Cues, Geriatrics and Gerontology, Verbal memory, medicine.symptom, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Amnesia is a key component of Alzheimer's disease (AD) and the most important feature of its clinical diagnosis but its specificity has recently been challenged. This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy. Patients' histological diagnoses were classified as pure AD, mixed AD, and non-AD pathologies. Data-driven automated classification procedures explored the correspondence between memory performance and pathological diagnoses. Classifications revealed 3 clusters of performance reflecting different levels of amnesia. Little correspondence between these clusters and the presence of AD pathology was retrieved. A third of patients with pure/mixed AD pathology were non-amnesic at presentation and ≈45% of patients without AD pathology were amnesic. Data-driven prediction of AD pathology based on memory also had a poor accuracy. Free and cued memory assessments are fair tools to diagnose an amnesic syndrome but lack accuracy to predict AD pathology.
Published: 2020
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32. A Spatial Decision Eye-Tracking Task in Patients with Prodromal and Mild Alzheimer’s Disease

Author: Léa Declerck, Brice Laurens, Maité Formaglio, Mathieu Ceccaldi, Vincent Planche, Lejla Koric, C. Tilikete, Magali Seassau, Stéphanie Cubizolle, Sandrine Dupouy, Françcois Tison, Alain Vighetto, Université de Bordeaux (UB), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Neuro-Ophtalmologie [Bron], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Pierre Wertheimer - HCL [Bron], Hospices Civils de Lyon (HCL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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 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], and 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)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Eye Movements, Prodromal Symptoms, Disease, Audiology, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Visual memory, Alzheimer Disease, medicine, Saccades, Humans, Clinical significance, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, General Neuroscience, Neuropsychology, Cognition, General Medicine, Anticipation, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Case-Control Studies, Disease Progression, Eye tracking, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Spatial Navigation
Abstract: BACKGROUND/OBJECTIVE Performances on spatial decision eye-tracking tasks are known to be impaired in patients with moderate Alzheimer's disease (AD), but the clinical relevance of this deficit during earlier stages of AD remains unclear. METHODS This study recruited patients with amnestic mild cognitive impairment (aMCI, prodromal AD), patients with mild AD, and age-matched controls from three French memory clinics. Participants' ability to make spatial judgments and decisions was assessed with an eye-tracking system, and cognitive performance on conventional neuropsychological tests was evaluated. RESULTS We enrolled 26 controls, 25 aMCI patients (median Mini-Mental State Exam [MMSE] 26), and 23 mild-AD patients (median MMSE 23). Patients with mild AD had higher error rates on the spatial decision task than aMCI patients and controls (32.4% versus 23.5%; p
Published: 2019
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33. Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer’s Disease Before 51 Years

Author: Aline Zarea, Eloi Magnin, Stéphane Epelbaum, Claire Paquet, Valérie Chauviré, Florence Pasquier, Anne Boland, Marie Sarazin, David Wallon, Bruno Salomon, Dominique Campion, Olivier Godefroy, Olivier Martinaud, Mathilde Sauvée, Sophie Auriacombe, Cecilia Marelli, Frédérique Etcharry-Bouyx, Gaël Nicolas, Jean-François Deleuze, Anne-Claire Richard, Vincent de la Sayette, Audrey Gabelle, Thérèse Rivasseau Jonveaux, Stéphane Rousseau, Jérémie Pariente, Mathieu Ceccaldi, Maïté Formaglio, Anne Rovelet-Lecrux, Didier Hannequin, Adeline Rollin-Sillaire, Bernard Croisile, Isabelle Le Ber, Morgane Lacour, Olivier Quenez, Olivier Rouaud, Muriel Quillard-Muraine, Claire Boutoleau-Bretonnière, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Rouen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Hospices Civils de Lyon (HCL), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, MESH: Mutation, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, MESH: Whole Exome Sequencing, Alzheimer Disease, Risk Factors, MESH: Risk Factors, MESH: Amyloid beta-Protein Precursor, PSEN2, Genotype, Genetic variation, Presenilin-2, Exome Sequencing, medicine, PSEN1, Presenilin-1, Humans, Early-onset Alzheimer's disease, Genetic Predisposition to Disease, Risk factor, Allele, Exome sequencing, Genetics, MESH: Humans, MESH: Middle Aged, business.industry, General Neuroscience, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, medicine.disease, MESH: Presenilin-1, MESH: Male, 3. Good health, MESH: Presenilin-2, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Female, Geriatrics and Gerontology, business, MESH: Female, 030217 neurology & neurosurgery, MESH: Alzheimer Disease
Abstract: International audience; Background:Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer’s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.Objective:To describe the proportion of each genetic variation among patients with very young-onset sporadic AD. Methods:We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved. Results:Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset (p
Published: 2019
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34. O1‐06‐04: ASSOCIATION BETWEEN HYPERTENSION AND ALZHEIMER'S DISEASE AND RELATED CAUSES OF DEMENTIA: A PATHWAYS ANALYSIS IN THE MEMENTO COHORT

Author: Jérémie Lespinasse, Isabelle Rouch-Leroyer, Florence Pasquier, Olivier Moreaud, Audrey Gabelle, Jean-François Mangin, Athanasios Benetos, Pierre Vandel, Renaud David, Carole Dufouil, François Tison, Cédric Annweiler, Frédéric Blanc, Claire Paquet, Bruno Dubois, Cécile Proust-Lima, Olivier Hanon, Marie-Odile Habert, Geneviève Chêne, Pierre Jean Ousset, Marie Chupin, François Sellal, Olivier Godefroy, Isabelle Jalenques, Mathieu Ceccaldi, and Hugo Bertin
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cohort, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business, Association (psychology)
Published: 2019
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35. Reduced Regional Cortical Thickness Rate of Change in Donepezil-Treated Subjects With Suspected Prodromal Alzheimer’s Disease

Author: Marie Chupin, Enrica Cavedo, Marie Sarazin, Guy Louis Tisserand, Florence Pasquier, Nadine Girard, Olivier Rouaud, Harald Hampel, Samantha Galluzzi, Alain Vighetto, Didier Dormont, Bruno Dubois, Simone Lista, Christine Delmaire, Olivier Colliot, Alain Bonafe, Stéphane Lehéricy, Bernard Croisile, Frédéric Ricolfi, Mathieu Ceccaldi, Françoise Duveau, Jacques Touchon, Pierre-Jean Ousset, Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Casselardit - Junod, Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), IRCCS Fatebenefratelli - Brescia, Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), IEF, Université Paris-Sud - Paris 11 (UP11), Eisai, CHU Saint-Antoine [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Inria de Paris, Service de Neuroradiologie [CHU Pitié-Salpêtrière], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, and Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV]
Subjects: Male, 0301 basic medicine, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, law.invention, 0302 clinical medicine, Piperidines, Randomized controlled trial, law, Outcome Assessment, Health Care, Donepezil, Longitudinal Studies, Nootropic Agents, Aged, 80 and over, Cerebral Cortex, medicine.diagnostic_test, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Cerebral cortex, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Indans, Disease Progression, Cardiology, Female, Alzheimer's disease, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, medicine.drug, medicine.medical_specialty, Prodromal Symptoms, Placebo, 03 medical and health sciences, Double-Blind Method, Alzheimer Disease, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Dementia, Cognitive Dysfunction, Aged, Surrogate endpoint, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Amnesia, Neuroscience, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day). The study started in November 2006 and concluded in August 2010. All subjects underwent 2 brain structural magnetic resonance imaging (MRI) scans, at baseline and at the end of the trial. Structural MRI images had been processed using the automated pipeline for longitudinal segmentation and surface reconstruction implemented in FreeSurfer. The primary outcome measure of this post hoc study was the annualized percentage change (APC) of cortical thickness. RESULTS: The donepezil group exhibited reduced APC cortical thinning compared to placebo in the rostral anterior cingulate (right: P = .048; left: P = .032), the orbitofrontal (right: P = .012; left: P < .048), and the right inferior frontal (P = .022) cortices and in the right insula (P = .010). These results were not statistically significant after Bonferroni correction likely due to insufficient power for cortical thickness measurements in the study group powered for the predefined hippocampus outcome. CONCLUSIONS: Our findings support the hypothesis that cortical thickness is a reliable candidate surrogate outcome in early predementia AD trials. In addition, donepezil treatment may have an impact on cortical structure/morphology in areas innervated by the medial and lateral cholinergic pathways. BACKGROUND: ClinicalTrials.gov identifier: NCT00403520. 77
Published: 2016
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36. Collaborative efforts to prevent Alzheimer’s disease

Author: Jacques Touchon, J. Rosenbaum, Audrey Gabelle, Pierre N. Tariot, Howard Feldman, Maria C. Carrillo, S. Andrieu, Bruno Vellas, Paul S. Aisen, J.-F. Dartiques, M. Weiner, Maria Isaac, Reisa A. Sperling, Mathieu Ceccaldi, L. J. Fitten, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps [Toulouse], Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Institut de Neurosciences des Systèmes ( INS ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bordeaux ( UB ), Département de neurologie [Montpellier], Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM)
Subjects: Gerontology, Nutrition and Dietetics, Geriatrics gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MEDLINE, Medicine (miscellaneous), [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Disease, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Geriatrics and Gerontology, Alzheimer's disease, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Quality of Life Research
Abstract: Author(s): Touchon, J; Rosenbaum, J; Aisen, P; Andrieu, S; Carrillo, MC; Ceccaldi, M; Dartiques, J-F; Feldman, H; Gabelle, A; Isaac, M; Fitten, LJ; Sperling, RA; Vellas, B; Tariot, P; Weiner, M
Published: 2017
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37. Editorial: Facing up to the complexity of neuro degenerative disorders in order to deal with them more effectively

Author: Mathieu Ceccaldi, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Neurology, Computer science, Order (business), Degenerative Disorder, Management science, [SCCO.NEUR]Cognitive science/Neuroscience, MEDLINE, Neurology (clinical), ComputingMilieux_MISCELLANEOUS, Introductory Journal Article
Abstract: International audience
Published: 2019
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38. Étude en TEP cérébrale au 18FDG de l’impact du stress dans la cohorte MEMENTO chez des patients non-déments consultant un centre mémoire

Author: Hugo Bertin, Lejla Koric, Carole Dufouil, Geneviève Chêne, Eric Guedj, Vincent Bouteloup, M.-O. Habert, Mathieu Ceccaldi, and J. Wojak
Subjects: Radiological and Ultrasound Technology, Biophysics, Radiology, Nuclear Medicine and imaging
Abstract: Introduction Les evenements stressants de vie pourraient contribuer aux plaintes et deficits au stade de deficit cognitif leger (mild cognitive impairment), et a une progression plus rapide vers la demence de type Alzheimer (MA). L’objectif de ce travail est de preciser l’impact du stress chez des patients non-dements consultant un centre memoire et d’etudier son substrat en TEP cerebrale au 18FDG. Materiels et methodes Cette etude s’appuie sur la cohorte MEMENTO, une cohorte nationale clinique de 2323 participants. Nous avons identifie a l’inclusion 512 sujets presentant une plainte cognitive subjective ou un deficit cognitif leger, pour lesquels les variables suivantes etaient disponibles : âge, sexe, niveau educatif, statut tabagique, statut TEP amyloide, statut APO-E, CDR, MMSE, scores NPI, TEP au 18FDG et echelle de stress. Cette derniere etait cotee entre 0 et 10 (stress maximal) par les patients en fonction de la gene ressentie. Des analyses statistiques ont ete conduites pour etablir le lien entre ces variables. Une analyse SPM12 de correlation TEP au 18FDG voxel-a-voxel sur cerveau entier a egalement ete realisee selon le niveau de stress rapporte (en tenant compte des co-variables suivantes : âge, sexe, niveau educatif, statut amyloide, CDR, MMSE). Resultats Le score moyen a l’echelle de stress sur les 512 sujets de l’echantillon analytique etait de 3,5 (ecart-type) 2,6 (min 0–max 10). Ce score n’etait pas modifie selon les statuts APO-E ɛ4, TEP amyloide ou tabagique (ANOVA p > 0,25). Les personnes dont les scores de stress etaient les plus eleves etaient plus frequemment des femmes, jeunes, moins diplomees, avec une plus grande severite aux scores CDR, MMSE et NPI (ANOVA/Pearson, p 180). Conclusion Le stress associe aux evenements de vie chez des patients non-dements consultant en centre memoire est associe a une plus grande severite clinique, independante du statut APO-E ɛ4 et amyloide, avec une dysfonction metabolique du lobe temporal droit en TEP au 18FDG. Des analyses complementaires seront necessaires pour preciser si ce profil est associe a une reorganisation differentielle des reseaux cerebraux associes a la MA avec un possible impact sur la conversion vers une demence.
Published: 2019
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39. [O1–13–05]: IS THE PROSPECTIVE ASSOCIATION BETWEEN DOMAIN‐SPECIFIC COGNITIVE IMPAIRMENT AND INCIDENT DEMENTIA MODIFIED BY EDUCATION? THE MEMENTO COHORT

Author: Frédéric Blanc, Jacques Hugon, Bruno Dubois, Serge Belliard, Mathieu Ceccaldi, Sophie Auriacombe, Olivier Hanon, Olivier Rouaud, Geneviève Chêne, Pierre Jean Ousset, Catherine Thomas-Antérion, Renaud David, Florence Pasquier, Alexandra Foubert-Samier, Carole Dufouil, Pierre Krolak Salmon, and Audrey Gabelle
Subjects: Epidemiology, business.industry, Health Policy, medicine.disease, Domain (software engineering), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, Medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment, Association (psychology), Clinical psychology
Published: 2017
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40. [O2–10–05]: SHORT‐TERM PREDICTION OF CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO DEMENTIA IN PATIENTS IN THE MEMENTO COHORT, 2011–2016

Author: Renaud David, Jean-François Mangin, Emilie Beaufils, Clélia Favary, Florence Pasquier, Jacques Hugon, Vincent Bouteloup, Bruno Vellas, Frédéric Blanc, Marie Chupin, Bruno Dubois, Carole Dufouil, Olivier Hanon, Pierre Krolak Salmon, Olivier Rouaud, Mathieu Ceccaldi, Geneviève Chêne, Audrey Gabelle, and François Tison
Subjects: Pediatrics, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, medicine.disease, Term (time), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Cohort, medicine, Dementia, In patient, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment
Published: 2017
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41. [Towards a national strategy on the diagnosis of neurocognitive disorders. A shared approach among the French National College of General Practitioners and specialists of neurocognitive disorders]

Author: Pierre, Krolak-Salmon, Laurent, Letrilliart, Mathieu, Ceccaldi, Sandrine, Andrieu, Olivier, Guérin, Bruno, Dubois, Bruno, Brochet, Pierre, Vandel, Claude, Jeandel, Armelle, Leperre-Desplanques, Michel, Clanet, and Pierre-Louis, Druais
Subjects: Aged, 80 and over, Neurologic Examination, Health Policy, Mental Disorders, General Practice, Neurocognitive Disorders, Neuroimaging, Mental Status and Dementia Tests, Diagnosis, Differential, Activities of Daily Living, Humans, Medicine, Dementia, Interdisciplinary Communication, France, Algorithms, Biomarkers, Societies, Medical
Abstract: Neurocognitive disorders leading to progressive cognitive, functional and behavioural impairment are often undiagnosed or diagnosed lately. But tailored care and therapeutics help in implementing secondary and tertiary prevention dynamics aiming at preserving quality of life and delaying, anticipating or preventing behavioural crisis and severe stages of dementia. Moreover, the diagnosis of numerous diseases induces specific care and therapeutics, as well access to research and clinical trials. For the first time, the representatives of the National College of General Practitioners, the French Federation of Memory Centres, the French Federation of Gerontology and Geriatrics, the French Federation of Neurology, the French Society of Psychogeriatrics and the national plan on neurodegenerative diseases propose a graduated and tailored diagnosis strategy involving primary care and specialists of neurocognitive disorders. This strategy has been built in the context of the national plan on neurodegenerative diseases, the European Joint Action "Act on dementia", and has been consensually agreed after a seminar animated by the National College of General Practitioners in March 2017.
Published: 2017

42. Added value of

Author: Mathieu, Ceccaldi, Thérèse, Jonveaux, Antoine, Verger, Pierre, Krolak-Salmon, Claire, Houzard, Olivier, Godefroy, Trevor, Shields, Audrey, Perrotin, Rossella, Gismondi, Santiago, Bullich, Aleksandar, Jovalekic, Nicola, Raffa, Florence, Pasquier, Franck, Semah, Bruno, Dubois, Marie-Odile, Habert, David, Wallon, Mathieu, Chastan, Pierre, Payoux, Andrew, Stephens, and Nathalie, Sastre-Hengan
Subjects: Diagnosis, Differential, Male, Amyloid, Aniline Compounds, Positron-Emission Tomography, Stilbenes, Brain, Humans, Dementia, Female, France, Radiopharmaceuticals, Aged
Abstract: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.
Published: 2017

43. The need for harmonisation and innovation of neuropsychological assessment in neurodegenerative dementias in Europe

Author: Sietske A.M. Sikkes, Jean-François Démonet, Stefano F. Cappa, Pieter Jelle Visser, Bruno Dubois, Alberto Costa, Emrah Düzel, Fabienne Collette, Sergio Della Sala, Peter J. Nestor, Wiesje M. van der Flier, Eric Salmon, Carlo Caltagirone, Sebastian J. Crutch, Thomas H. Bak, Mathieu Ceccaldi, Sokratis G. Papageorgiou, Paolo Caffarra, Pietro Tiraboschi, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MILD COGNITIVE IMPAIRMENT, Standardization, Applied psychology, Review, Neuropsychological Tests, lcsh:RC346-429, cognitive assessment, Behavioural assessment, 0302 clinical medicine, longitudinal studies, POSTERIOR CORTICAL ATROPHY, Neuropsychological assessment, FRONTAL ASSESSMENT BATTERY, ComputingMilieux_MISCELLANEOUS, behavioural assessment, medicine.diagnostic_test, Longitudinal studies, 05 social sciences, Montreal Cognitive Assessment, Cognition, neurodegenerative dementia, Neuropsychological test, PREDEMENTIA ALZHEIMERS-DISEASE, 3. Good health, Europe, Neurology, Neurodegenerative dementia, Neuropsychological tests, INSTRUMENTAL ACTIVITIES, Settore MED/26 - Neurologia, Psychology, medicine.medical_specialty, Cognitive Neuroscience, VARIANT FRONTOTEMPORAL DEMENTIA, DIAGNOSTIC-CRITERIA, European research, MINI-MENTAL-STATE, PRIMARY PROGRESSIVE APHASIA, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, Cognitive assessment, TERM-MEMORY BINDING, medicine, Dementia, Humans, 0501 psychology and cognitive sciences, ddc:610, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Mini–Mental State Examination, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, diagnosis [Dementia], Neurology (clinical), 030217 neurology & neurosurgery, Geriatric psychiatry
Abstract: Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status. Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a “big data” common data set. We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe. A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries.
Published: 2017
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44. Changes of metabolism and functional connectivity in late-onset deafness: Evidence from cerebral

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

45. O4-07-05: NIA-AA RESEARCH FRAMEWORK: APPLICATION TO THE FRENCH POPULATION BY INFERENCE FROM THE MEMENTO COHORT

Author: Cédric Annweiler, Audrey Gabelle, Olivier Hanon, Mathieu Ceccaldi, Armelle Gentric, Pierre Krolak Salmon, Catherine Belin, Marc Paccalin, Yannick Béjot, Emilie Beaufils, Pierre Jean Ousset, Florence Pasquier, Maxime Locatelli, Marie-Odile Habert, Marie Chupin, Claire Paquet, Claire Boutoleau-Bretonnière, François Tison, Vincent Bouteloup, Jean-François Mangin, David Wallon, Bruno Dubois, Carole Dufouil, Geneviève Chêne, and Frédéric Blanc
Subjects: education.field_of_study, Epidemiology, Health Policy, Population, Inference, Genealogy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Conceptual framework, Cohort, Neurology (clinical), Geriatrics and Gerontology, Psychology, education
Published: 2019
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46. P4-358: DIAGNOSTIC VALUE OF THE AMNESTIC SYNDROME FOR ALZHEIMER'S DISEASE: A CLINICOPATHOLOGICAL STUDY

Author: Isabelle Le Ber, Sophie Auriacombe, Marie Sarazin, Didier Hannequin, Mathieu Ceccaldi, Vincent Deramecourt, Bruno Dubois, Charles Duyckaerts, Florence Pasquier, Maxime Bertoux, Pascaline Cassagnaud, and Thibaud Lebouvier
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Amnestic syndrome, Gastroenterology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Value (mathematics)
Published: 2019
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47. Quelle place pour les biomarqueurs de pathologie dans le diagnostic de maladie d’Alzheimer ?

Author: Gabelle-Deloustal, Audrey, primary and Mathieu, Ceccaldi, additional
Published: 2018
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48. Cognitive changes in mild cognitive impairment patients with impaired visual recognition memory

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

Author: Jean-Philippe Ranjeva, Mathieu Ceccaldi, Maxime Guye, Claude Gueriot, Olivier Felician, Mira Didic, Valérie Chanoine, Natalina Gour, Lejla Koric, and Sylviane Confort-Gouny
Subjects: Radiological and Ultrasound Technology, medicine.diagnostic_test, Magnetic resonance imaging, Late onset, medicine.disease, Executive functions, Temporal lobe, Basal (phylogenetics), Atrophy, Neurology, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Neuropsychological assessment, Anatomy, Psychology, Neuroscience, Default mode network
Abstract: At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting-state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso-lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double-dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes.
Published: 2013
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50. Prise de poids, démence et syndrome cérébelleux sensible à la doxycycline : un probable nouveau cas lié à T. whipplei

Author: Didier Raoult, Mathieu Ceccaldi, Florence Fenollar, Lejla Koric, J.-C. Lagier, and Eric Guedj
Subjects: Gastroenterology, Internal Medicine
Abstract: Resume Introduction La maladie de Whipple est une maladie infectieuse rare due a Tropheryma whipplei , bacterie parfois responsable d’atteintes neurologiques graves isolees (25 cas rapportes dans la litterature), diagnostiquees le plus souvent par la positivite d’une PCR specifique sur le LCR. Observation Nous rapportons le troisieme cas d’un syndrome associant obesite, demence et ataxie cerebelleuse. Le bilan etiologique etait sans particularite ; seule une PCR T. whipplei dans la salive s’averait fortement positive, la serologie etant en faveur d’un portage de la bacterie. Le PET-scanner cerebral au 18 FDG retrouvait un hypometabolisme frontal. Une antibiotherapie d’epreuve par doxycycline permettait une regression partielle des manifestations neurologiques et une perte de poids moderee et differee, l’hypometabolisme au PET-scanner regressant sous traitement. Conclusion Le syndrome associant obesite, demence et ataxie cerebelleuse est une nouvelle entite clinique d’infection a T. whipplei . Un traitement d’epreuve par doxycycline peut aider au diagnostic et le PET-scanner pourrait etre un des elements du suivi.
Published: 2013
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