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1,471 results on '"Gabelle A"'

301. Prospective associations between physical activity levels and white matter integrity in older adults: results from the MAPT study

Author: Maltais, Mathieu, primary, Rolland, Yves, additional, Boisvert-Vigneault, Katherine, additional, Perus, Lisa, additional, Mangin, Jean-François, additional, Grigis, Antoine, additional, Chupin, Marie, additional, Bouyahia, Ali, additional, Gabelle, Audrey, additional, Delrieux, Julien, additional, Vellas, Bruno, additional, and de Souto Barreto, Philipe, additional
Published: 2020
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302. Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial

Author: King, Madeleine T, primary, Link, Emma K, additional, Whelan, Tim J, additional, Olivotto, Ivo A, additional, Kunkler, Ian, additional, Westenberg, Antonia Helen, additional, Gruber, Guenther, additional, Schofield, Penny, additional, Chua, Boon H, additional, Phillips, Claire, additional, Bryant, Guy, additional, Westenberg, Helen, additional, Purohit, Om Pra-Kesh, additional, Ahern, Verity, additional, Graham, Peter, additional, Akra, Mohamed, additional, McArdle, Orla, additional, O'Brien, Peter, additional, Ludbrook, Jane, additional, Harvey, Jennifer, additional, Maduro, John H, additional, Gabelle-Flandin, Isabelle, additional, Kirkove, Carine, additional, Bedi, Carolyn, additional, Martin, Joseph, additional, Vu, Tony, additional, Muanza, Theirry, additional, Neal, Anthony, additional, Courdi, Adel, additional, Thariat, Juliette, additional, Rakovitch, Eileen, additional, Daniels, Laurien, additional, van Hezewijk, Marjan, additional, Cwajna, Wlasyslawa, additional, Roelstraete, Adelheid, additional, van Baardwijk, Angela, additional, Russel, Nicola, additional, Koch, Anne, additional, Croke, Jennifer, additional, Locke, Imogen, additional, Jeal, Peter, additional, Walker, Quenten, additional, Thuraisingham, Kandeepeepan, additional, Chauduri, Anupam, additional, Joseph, David, additional, Taylor, Mandy, additional, Vanderkam, Sabine, additional, Woo, Tony, additional, Tang, Johann, additional, Yassa, Michael, additional, Wai, Elaine, additional, Hewitt, Susan, additional, Mahmood, Shazia, additional, Gilmore, Jennifer, additional, Ofi, Bolante, additional, Bahl, Amit, additional, Vujovic, Olga, additional, Yu, Edward, additional, Le, Duc, additional, Kong, Iwa, additional, Nichol, Alan, additional, Bijker, Nina, additional, Delaney, Geoff, additional, Feigen, Malcolm, additional, Lim, Adeline, additional, Chao, Michael, additional, Latham, Margaret, additional, Algurafi, Hafiz, additional, Tausch, Christoph, additional, Khoo, Eric, additional, Leung, Sam, additional, Taylor, Karen, additional, Senthi, Sasha, additional, Stevens, Andrea, additional, Chaudhuri, Abhro, additional, Cleator, Susan, additional, Brunt, Adrian Murray, additional, Babington, Scott, additional, Christie, David, additional, Zwahlen, Daniel, additional, Schratzenstaller, Ulrich, additional, Masson, Laurence, additional, Storey, Nicola, additional, Kumar, Eshwar, additional, Sherwin, Liz, additional, Weytjens, Reinhilde, additional, Ravi, Sharma, additional, Lawton, Patricia, additional, Angell, Ruth, additional, Round, Glenys, additional, Allen, Angela, additional, Thotathil, Ziad, additional, Anthes, Margaret, additional, Reuter, Christiane, additional, Pettit, Laura, additional, Zissiadis, Yvonne, additional, Elder, Christine, additional, Verbeek-de Kanter, Antoinette, additional, Lirette, Andree, additional, Plasswilm, Ludwig, additional, Spooner, David, additional, Hoar, Fiona, additional, Mohamed, Islam, additional, Lossl, Kristina, additional, Loo, Vivienne, additional, Richetti, Antonella, additional, Evans, Tamasin, additional, Hennessy, Aisling, additional, El-Mallah, Medhat, additional, Skala, Marketa, additional, Awad, Raef, additional, Germain, Isabelle, additional, Mitine, Carine, additional, Van Parijs, Hilde, additional, Churn, Mark, additional, Walji, Nawaz, additional, Francis, Michael, additional, Stellamans, Karin, additional, Gruber, Gunther, additional, Ivaldi, Giovanni, additional, Alhasso, Abdulla, additional, Kenny, Lizbeth, additional, Tiver, Ken, additional, Griffin, Matthew, additional, Lamoury, Gillian, additional, Trovo, Marco, additional, Algufarfi, Hafiz, additional, Lah, Minjae, additional, Carruthers, Scott, additional, Papadatos, George, additional, Paardekooper, Gabriel, additional, Persic, Mojca, additional, and Lavery, Bernadette, additional
Published: 2020
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303. Re: Prospective Associations between Diffusion Tensor Imaging Parameters and Frailty in Older Adults

Author: Maltais, Mathieu, primary, Souto Barreto, Philipe, additional, Perus, Lisa, additional, Mangin, Jean‐François, additional, Grigis, Antoine, additional, Chupin, Marie, additional, Bouyahia, Ali, additional, Gabelle, Audrey, additional, Delrieux, Julien, additional, Rolland, Yves, additional, and Vellas, Bruno, additional
Published: 2020
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304. Cerebrospinal Fluid and Plasma Biomarkers do not Differ in the Presenile and Late-Onset Behavioral Variants of Frontotemporal Dementia

Author: Marelli, Cecilia, primary, Hourregue, Claire, additional, Gutierrez, Laure-Anne, additional, Paquet, Claire, additional, Menjot de Champfleur, Nicolas, additional, De Verbizier, Delphine, additional, Jacob, Melissa, additional, Dubois, Jonathan, additional, Maleska, Aleksandra Maceski, additional, Hirtz, Christophe, additional, Navucet, Sophie, additional, Bennys, Karim, additional, Dumurgier, Julien, additional, Cognat, Emmanuel, additional, Berr, Claudine, additional, Magnin, Eloi, additional, Lehmann, Sylvain, additional, and Gabelle, Audrey, additional
Published: 2020
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305. Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer’s disease and PET amyloid-positive patient identification

Author: Barthélemy, Nicolas R., primary, Bateman, Randall J., additional, Hirtz, Christophe, additional, Marin, Philippe, additional, Becher, François, additional, Sato, Chihiro, additional, Gabelle, Audrey, additional, and Lehmann, Sylvain, additional
Published: 2020
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306. Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of mitochondrial substrates

Author: Motor Neuron Disease Association, Wellcome Trust, University of Sheffield, University of Dundee, University College London, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Mutua Madrileña, Fundación Ramón Areces, Bartolomé Robledo, Fernando [0000-0001-9322-8933], Esteras, Noemí [0000-0002-7938-6131], Martín-Requero, Ángeles [0000-0002-3416-9440], Boutoleau-Bretonnière, Claire [0000-0001-9051-6315], Gabelle, Audrey [0000-0002-7648-9194], Ber, Isabelle Le [0000-0002-2508-5181], Honda, Tadashi [0000-0003-0746-9453], Dinkova-Kostova, Albena T. [0000-0003-0316-9859], Hardy, John A. [0000-0002-3122-0423], Carro, Eva [0000-0002-6504-4579], Abramov, Andrey Yurevich [0000-0002-7646-7235], Bartolomé Robledo, Fernando, Esteras, Noemí, Martín-Requero, Ángeles, Boutoleau-Bretonnière, Claire, Vercelletto, Martine, Gabelle, Audrey, Ber, Isabelle Le, Honda, Tadashi, Dinkova-Kostova, Albena T., Hardy, John A., Carro, Eva, Abramov, Andrey Yurevich, Motor Neuron Disease Association, Wellcome Trust, University of Sheffield, University of Dundee, University College London, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Mutua Madrileña, Fundación Ramón Areces, Bartolomé Robledo, Fernando [0000-0001-9322-8933], Esteras, Noemí [0000-0002-7938-6131], Martín-Requero, Ángeles [0000-0002-3416-9440], Boutoleau-Bretonnière, Claire [0000-0001-9051-6315], Gabelle, Audrey [0000-0002-7648-9194], Ber, Isabelle Le [0000-0002-2508-5181], Honda, Tadashi [0000-0003-0746-9453], Dinkova-Kostova, Albena T. [0000-0003-0316-9859], Hardy, John A. [0000-0002-3122-0423], Carro, Eva [0000-0002-6504-4579], Abramov, Andrey Yurevich [0000-0002-7646-7235], Bartolomé Robledo, Fernando, Esteras, Noemí, Martín-Requero, Ángeles, Boutoleau-Bretonnière, Claire, Vercelletto, Martine, Gabelle, Audrey, Ber, Isabelle Le, Honda, Tadashi, Dinkova-Kostova, Albena T., Hardy, John A., Carro, Eva, and Abramov, Andrey Yurevich
Abstract: Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62 deficiency is associated with inhibited complex I mitochondrial respiration due to lack of NADH for the electron transport chain.This deficiency was also associated with increased levels of NADPH reflecting a higher activation of pentose phosphate pathway as this is accompanied with higher cytosolic reduced glutathione (GSH)levels. Complex I inhibition resulted in lower mitochondrial membrane potential and higher cytosolic ROS production. Pharmacological activation of transcription factor Nrf2 increased mitochondrial NADH levels and restored mitochondrial membrane potential in p62-deficient cells. Our results suggest that the phenotype is caused by a loss-of-function effect, because similar alterations were found both in the mutant fibroblasts and the p62 KD model. These findings highlight the implication of energy metabolism in pathophysiological events associated with p62 deficiency.
Published: 2017

307. Sex‐specific association between neighborhood characteristics and dementia: The Three‐City cohort

Author: Noémie Letellier, Catherine Helmer, Laure-Anne Gutierrez, Emmanuelle Cadot, Isabelle Carrière, Jean-François Dartigues, Claudine Berr, Carole Dufouil, Audrey Gabelle, 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), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Equipe LEHA - Inserm U1219 [Bordeaux], 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)-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), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Equipe VINTAGE - Inserm U1219 [Bordeaux], Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Agence Nationale de la Recherche ANR PNR 2006 (ANR/DEDD/PNRA/PROJ/200206-01-01) and Longvie 2007 (LVIE-003-01)., ANR-07-LVIE-0003,COGICARE,Histoire naturelle du déclin cognitif et du besoin de soins chez le sujet âgé(2007), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Male, Gerontology, Epidemiology, Deprivation score, Population, Living environment, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sex Factors, 0302 clinical medicine, Developmental Neuroscience, Residence Characteristics, medicine, Humans, Dementia, 030212 general & internal medicine, Cities, Prospective cohort study, education, Socioeconomic status, Aged, education.field_of_study, Neighborhood, Proportional hazards model, Health Policy, Incidence (epidemiology), Gender, medicine.disease, Confidence interval, Psychiatry and Mental health, Socioeconomic Factors, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, Psychology, 030217 neurology & neurosurgery
Abstract: International audience; INTRODUCTION:The living environment affects general health and may influence cognitive aging; however, the relationships between neighborhood characteristics and dementia are still poorly understood.METHODS:We used data from a French population-based prospective study (the Three-City cohort) that included 7016 participants aged 65 years and older with a 12-year follow-up. We used principal components analysis of neighborhood composition indicators to construct the Three-City deprivation score. To study its impact on dementia incidence, we performed survival analyses using a marginal Cox model to take into account intraneighborhood correlations. As interaction with sex was significant, analyses were stratified by sex.RESULTS:Even after controlling on individual factors, women living in deprived neighborhoods were at higher risk of dementia (hazard ratio = 1.29, 95% confidence interval 1.00-1.67) and Alzheimer's disease (hazard ratio = 1.42, 95% confidence interval 1.09-1.84). No association was found for men.DISCUSSION:Living in a deprived neighborhood is associated with higher risk of dementia in women.
Published: 2017

308. 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: Cognitive aging, Cohort studies, Neuroimaging, Alzheimer’s disease, Natural history studies (prognosis), lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429, lcsh:RC321-571
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

309. Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process

Author: Philippe Robert, Yves Dauvilliers, Sylvain Lehmann, Audrey Gabelle, Isabelle Jaussent, Caroline Grasselli, Sophie Navucet, Christophe Hirtz, Jérôme Vialaret, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioprojet-Biotech, Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, 0301 basic medicine, Amyloid, Aging, medicine.medical_specialty, Disease, 03 medical and health sciences, chemistry.chemical_compound, Orexin-A, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Nighttime sleep, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Wakefulness, Cognitive impairment, Aged, Aged, 80 and over, Orexins, Amyloid beta-Peptides, Methylhistamines, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, General Neuroscience, Middle Aged, Sleep in non-human animals, Peptide Fragments, 3. Good health, Orexin, 030104 developmental biology, Endocrinology, chemistry, Alzheimer, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Geriatrics and Gerontology, Sleep, Psychology, Biomarkers, 030217 neurology & neurosurgery, Histamine, Developmental Biology
Abstract: International audience; To better understand how sleep/wake dysregulation affects Alzheimer's disease (AD), we compared the cerebrospinal fluid (CSF) orexin and histamine/tele-methylhistamine (HA/t-MHA) levels of 82 patients (41 probable-AD-high level of evidence, 41 mild cognitive impairment MCI-due-to-AD), 24 other neurologic disorders (OND) and 24 controls. We determined the relationships between these biomarkers, the CSF AD biomarkers concentrations, and the clinical sleep profile. CSF orexin-A but not HA/t-MHA levels were higher in MCI and AD than OND and controls. CSF orexin-A is correlated to CSF amyloid-β42in MCI and AD, independently of age, gender, MMSE, total-tau/phosphorylated-tau, HA or sleep parameters. Nighttime sleep duration was longer in MCI and AD patients than controls. In MCI, nighttime sleep duration negatively correlated with CSF amyloid-β42 and MMSE. To conclude, CSF orexin-A but not HA/t-HMA was upregulated in AD and correlated with amyloid-β42 level. Our data suggested a change in the sleep-wake pattern at an early stage of the disease that needs further investigation to deeply explain the mechanistic interplay between sleep and Alzheimer.
Published: 2017

310. Les biomarqueurs du liquide cérébro-spinal dans la maladie d’Alzheimer : un outil de recherche utile dans la pratique clinique courante des consultations mémoire pour les cas complexes

Author: Katell Peoc'h, F. Blanc, Julien Dumurgier, O. Bousiges, A. Gabelle, Didier Hannequin, Sylvain Lehmann, Elodie Bouaziz-Amar, pour le groupe ePLM, F. Pasquier, Jacques Hugon, C. Miguet-Alfonsi, B. Jung, D. Wallon, E. Magnin, Claire Paquet, M. Quillard, Jean-Louis Laplanche, and S. Bombois
Subjects: 0301 basic medicine, Gynecology, medicine.medical_specialty, Amyloid, biology, business.industry, Tau protein, Gastroenterology, Neurofibrillary tangle, Disease, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Csf biomarkers, Internal Medicine, medicine, biology.protein, Total Tau Protein, Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract: The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorite de sante) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.
Published: 2017

311. PO-1226: Safety and outcomes of concurrent immunotherapy and radiation therapy for melanoma brain metastases

Author: A. Desagneaux, M.T. Leccia, Julie Charles, I. Gabelle Flandin, C. Verry, A. Kastler, and A.-.M. Dols
Subjects: Oncology, medicine.medical_specialty, business.industry, Melanoma, medicine.medical_treatment, Hematology, Immunotherapy, medicine.disease, Radiation therapy, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business
Published: 2020

312. Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles.

Author: Delaby, Constance, Alcolea, Daniel, Hirtz, Christophe, Vialaret, Jérôme, Kindermans, Jana, Morichon, Lisa, Fortea, Juan, Belbin, Olivia, Gabelle, Audrey, Blennow, Kaj, Zetterberg, Henrik, Lleó, Alberto, and Lehmann, Sylvain
Subjects: CEREBROSPINAL fluid, TAU proteins, AMYLOID, BIOMARKERS, CEREBRAL amyloid angiopathy, LUMBAR puncture
Abstract: Introduction: Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined. Methods: We studied in two independent cohorts, the performance of blood biomarkers in detecting "nonpathological" (A−/T−/N−), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles. Results: Plasma Aβ1–42/Aβ1–40 ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A−/T−/N−) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection. Conclusion: The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents an attractive stratification strategy in the clinical management of patients visiting memory clinics. This could reduce the need for lumbar puncture and foreshadow the use of blood testing on larger populations. [ABSTRACT FROM AUTHOR]
Published: 2022
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313. Complaints of daytime sleepiness, insomnia, hypnotic use, and risk of dementia: a prospective cohort study in the elderly.

Author: Cavaillès, Clémence, Berr, Claudine, Helmer, Catherine, Gabelle, Audrey, Jaussent, Isabelle, and Dauvilliers, Yves
Subjects: DISEASE risk factors, SLEEP interruptions, DROWSINESS, COHORT analysis, VASCULAR dementia, CEREBRAL amyloid angiopathy
Abstract: Background: Sleep disturbances are common in elderly and occur frequently in dementia. The impact of excessive daytime sleepiness (EDS), insomnia complaints, sleep quality, and hypnotics on the risk of all-cause dementia, Alzheimer disease (AD), and dementia with vascular component (DVC) remains unclear, as does the association between sleep profile and plasma β-amyloid levels. Methods: Analyses were carried out on 6851 participants aged 65 years and over randomly recruited from three French cities and free of dementia at baseline. A structured interview and self-questionnaire assessed sleep complaints (EDS, insomnia complaints, sleep quality) and medications at baseline. Incident cases of dementia were diagnosed systematically over a 12-year period. Multivariate Cox models were used to estimate the risk of dementia associated with the sleep complaints considered individually and globally. Plasma β-amyloid levels were measured by an xMAP-based assay technology in 984 subjects. Results: After adjustment for socio-demographic characteristics, lifestyle, APOE-ε4, cardiovascular factors, and depressive status, EDS had a higher risk of all-cause dementia (HR = 1.21; 95%CI = [1.01–1.46]) and DVC (HR = 1.58; 95%CI = [1.07–2.32]) but not AD. Persistent use of hypnotics increased the risk for all-cause dementia, specifically AD (HR = 1.28; 95%CI = [1.04–1.58]), but not DVC. No association was found for insomnia complaints and sleep quality taken as individual factors or combined with EDS on the risk of dementia. No association was found between β-amyloid, sleep complaints, and incident dementia. Conclusions: The results suggest a deleterious role of EDS and hypnotics on dementia. Further studies are required to elucidate the mechanisms involved in these associations and whether its management can prevent the risk of dementia. [ABSTRACT FROM AUTHOR]
Published: 2022
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314. Trajectories of sleep duration and timing prior to dementia: a 14-year follow-up study

Author: Cavaillès, C., Carrière, I., Wagner, M., Gabelle, A., Berr, C., Jaussent, I., and Dauvilliers, Y.
Published: 2022
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315. A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Author: Dumurgier, Julien, Sabia, Séverine, Zetterberg, Henrik, Teunissen, Charlotte E., Hanseeuw, Bernard, Orellana, Adelina, Schraen, Susanna, Gabelle, Audrey, Boada, Mercè, Lebouvier, Thibaud, Willemse, Eline A.J., Cognat, Emmanuel, Ruiz, Agustin, Hourregue, Claire, Lilamand, Matthieu, Bouaziz-Amar, Elodie, Laplanche, Jean-Louis, Lehmann, Sylvain, Pasquier, Florence, Scheltens, Philip, Blennow, Kaj, Singh-Manoux, Archana, and Paquet, Claire
Published: 2022
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316. Prospective Associations Between Diffusion Tensor Imaging Parameters and Frailty in Older Adults

Author: Mathieu, Maltais, Philipe, de Souto Barreto, Lisa, Perus, Jean-François, Mangin, Antoine, Grigis, Marie, Chupin, Ali, Bouyahia, Audrey, Gabelle, Julien, Delrieux, Yves, Rolland, Bruno, Vellas, Sylvie, Caspar-Bauguil, Service NEUROSPIN (NEUROSPIN), 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, Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service Hospitalier Frédéric Joliot (SHFJ), Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Unité Baobab (BAOBAB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), 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), 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), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], 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), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and ANR-16-IDEX-0006,MUSE,MUSE(2016)
Subjects: Male, medicine.medical_specialty, brain health, Internal capsule, External capsule, diffusion magnetic resonance imagingfrailty, [SDV]Life Sciences [q-bio], physical capacity, White matter, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fractional anisotropy, Fasciculus, Medicine, Dementia, Humans, 030212 general & internal medicine, Prospective Studies, Aged, Aged, 80 and over, biology, Frailty, business.industry, Superior longitudinal fasciculus, medicine.disease, biology.organism_classification, White Matter, 3. Good health, medicine.anatomical_structure, Diffusion Magnetic Resonance Imaging, Cardiology, Disease Progression, Anisotropy, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: International audience; BACKGROUND: Cross-sectional associations have been found between frail individuals and worse white matter (WM) integrity. However, the prospective association between WM integrity and frailty is still unclear. Our objectives were to measure associations between WM integrity using diffusion tensor imaging (DTI) and the 5-year worsening of frailty in community-dwelling older adults. DESIGN: Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT). SETTING: Thirteen memory centers in France and Monaco between 2008 and 2011. PARTICIPANTS: Participants (mean age = 74.7 ± 3.9 years) with no dementia at baseline who had functional magnetic resonance imaging performed as part of the MAPT study (n = 227). MEASUREMENTS: Fractional anisotropy and mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) were acquired for 10 different brain regions. Frailty was assessed by the Fried frailty phenotype (score from 0 to 5, higher is worse) at up to seven time points for 5 years. Mixed effect ordinal logistic regression model was used to assess the prospective association between DTI parameters (independent variables) and frailty (dependent variable). All the analyses were adjusted for age, sex, baseline total intracranial volume, and the presence of one of the following cardiovascular risk factors (hypertension, diabetes, and/or hypercholesterolemia). RESULTS: A statistically significant association was found between the RD, AxD, and MD for different brain regions (anterior limb of internal capsule, external capsule, posterior corona radiata, posterior thalamic radiation, superior corona radiata, superior frontal occipital fasciculus, and superior longitudinal fasciculus) and worsening of frailty over 5 years after adjusting for multiple comparisons. CONCLUSIONS: This is the first study to show that WM integrity is associated with frailty in older adults. The mechanisms related to these results require further investigation. J Am Geriatr Soc 68:1050-1055, 2020.
Published: 2019

317. 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

318. Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice

Author: C Malaplate-Armand, Frédéric Blanc, Jean-Louis Laplanche, Constance Delaby, Eloi Magnin, Jacques Hugon, Audrey Gabelle, David Wallon, S. Schraen, Julien Dumurgier, Claire Paquet, Bernard Sablonnière, Elodie Bouaziz-Amar, Muriel Quillard-Muraine, Olivier Bousiges, Sylvain Lehmann, Katell Peoc'h, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, CHU Rouen, Normandie Université (NU), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie et de Biologie Moléculaire [AP-HP Hôpital Lariboisière] (Inserm U942), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), CCSD, Accord Elsevier, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, Tau protein, Context (language use), tau Proteins, Disease, Biochemistry, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Medicine, Dementia, Humans, Medical diagnosis, Aged, Aged, 80 and over, biology, Lewy body, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Biochemistry (medical), [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 14-3-3 protein, General Medicine, Middle Aged, Alzheimer's disease, medicine.disease, Phosphoproteins, Creutzfeldt-Jakob disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, business, Laboratories, Biomarkers, Frontotemporal dementia
Abstract: International audience; Context: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling.Patients and methods: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aβ 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis.Results: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aβ1-42 and Aβ1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aβ1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aβ1-42 concentrations 60 pg/mL.Conclusion: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.
Published: 2019

319. Relationships between objectives sleep parameters and brain amyloid load in subjects at risk for Alzheimer’s disease: the INSIGHT-preAD Study

Author: Marcel Levy Nogueira, Hovagim Bakardjian, Philippe Robert, Bruno Dubois, Marie-Odile Habert, Renaud David, Eric Ettore, Marine Sole, and Audrey Gabelle
Subjects: Male, medicine.medical_specialty, Disease, Neuropsychological Tests, Audiology, Hippocampus, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Physiology (medical), medicine, Humans, Cognitive Dysfunction, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Amyloid beta-Peptides, Aniline Compounds, business.industry, Neuropsychology, Brain, Cognition, Actigraphy, Amyloidosis, Magnetic Resonance Imaging, Sleep in non-human animals, Positron-Emission Tomography, Ambulatory, Cohort, Ethylene Glycols, Female, Neurology (clinical), Sleep onset, Sleep, business, 030217 neurology & neurosurgery
Abstract: Study Objectives Sleep changes have been associated with increased risks of developing cognitive disturbances and Alzheimer’s disease (AD). A bidirectional relation is underlined between amyloid-beta (Aß) and sleep disruptions. The sleep profile in participants at risk to develop AD is not fully deciphered. We aim to investigate sleep–wake changes with objective sleep measurements in elderly participants without cognitive impairment depending on their brain amyloid status, positive (Aß+) or negative (Aß−) based on standard absorption ratios (SUVr) positron emission tomography-florbetapir imaging. Methods Sixty-eight participants without cognitive impairment who have accepted to be involved in the sleep ancillary study from the InveStIGation of Alzheimer’s Predictors in Subjective Memory Complainers (INSIGHT-pre AD) cohort, aiming to record sleep profile based on the analyses of an ambulatory accelerometer-based assessment (seven consecutive 24-hour periods). Neuropsychological tests were performed and sleep parameters have been individualized by actigraph. Participants also underwent a magnetic resonance imaging scan to assess their hippocampal volume. Based on SUVr PET-florbetapir imaging, two groups Aß+ and Aß− were compared. Results Participants were divided into two groups: Aß+ (n = 24) and Aß− (n = 44). Except for the SUVr, the two subgroups were comparable. When looking to sleep parameters, increased sleep latency, sleep fragmentation (wake after sleep onset [WASO] score and awakenings) and worst sleep efficiency were associated with cortical brain amyloid load. Conclusion Actigraphic sleep parameters were associated with cortical brain amyloid load in participants at risk to develop AD. The detection of sleep abnormalities in those participants may be of interest to propose some preventive strategies.
Published: 2019

320. 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

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

Author: Noëlle Cardinaud, Francine Fontaine, Marie Paule Bonceour Martel, Danièle Begorre, Claire Vinel, Dominique Dubois, Serge Bordes, Charlotte Dupuy, Jean-François Dartigues, Lars Bäckman, Marie-Laure Pader, Colette Blatge, Jacques Touchon, Julien Delrieu, Karim Bennys, Miia Kivipelto, Pierre Payoux, Christian Vincent, Ileana Desormais, Françoise Hugon, Isabelle Saulnier, Michèle Allard, Pascale Olivier-Abbal, Patrick Manckoundia, Audrey Gabelle, Yannick Gasnier, Olivier Rouaud, Christine Malick-Loiseau, Carole Badufle, Christian Carpuat, Sophie Marilier, Sophie Peiffer, Stéphane Chanalet, Riitta Antikainen, Jean-Pierre Salles, Stéphanie Roth, Catherine Burdet, Pierre Livet, Nadège Barro-Belaygues, François Cotton, Tiia Ngandu, Pim van Gool, Alexandra Foubert, Eric P. Moll van Charante, Khaled Khales, Pierre-Jean Ousset, Hilkka Soininen, Valérie Faure, Sandrine Andrieu, Corinne Costes, Marie-Noelle-Cuffi, Frédéric Ricolfi, Pascale Rebaudet, Samira Misbah El Idrissi, Céline Caillaud, Marie Chupin, Alain Pesce, Françoise Lala, N. Costa, Emeline Combrouze, Carol Brayne, Bertrand Fougère, Michel Zanca, H. Villars, Sebastien Gonfrier, Fabrice Bonneville, Lynda Touati, Sandrine Cerda, Katri Hemio, Esko Levälahti, Jacques Darcourt, Philippe Robert, Christophe Morin, Brigitte Gilbert, Alain Bonafe, Catherine Faisant, Jacques Monteil, Lawrence Bories, Bram van de Groep, Edo Richard, Gabor Abellan van Kan, Valérie Quipourt, Marc Bonnefoy, Françoise Desclaux, Kristelle Sudres, Thierry Voisin, Timo E. Strandberg, Yves Rolland, Evelyne Franon, Susan Jongstra, Anna Stigsdotter-Neely, Marie-France Basset, Thierry Dantoine, Laurent Molinier, Tiina Laatikainen, Audrey Zueras, Jean-François Lefebvre, Claire Gédéon, Christelle Cantet, Jean-Pierre Clément, Jean-François Mangin, Aurélia Romano, François Chollet, Tuomo Hänninen, Yannick Meiller, Marie-Agnès Picat, Satu Havulinna, Tessa van Middelaar, Jenni Lehtisalo, Isabelle Marcet, Stéphanie Willebois, Christophe Cognard, Hélène Derumeaux, Cécile Pays, Laurence Bernard-Bourzeix, Sylvie Belleville, Anne Hitzel, Cathrien Beishuizen, Ali Bouhayia, Sylvie Chaillou, Bruno Lapoujade, Franck Le Duff, Bruno Vellas, Michael Li Yung Tong, Marieke P. Hoevenaar-Blom, Cecilia Marelli, Rainer Rauramaa, Flavien Terracol, Marko Gronholm, Fleur Delva, Mariagnese Barbera, Sandrine Louchart, Isabelle Carrié, Lauréane Brigitte, Alina Solomon, Bertrand Perret, Claire Gervais, Jaakko Tuomilehto, Carole Dufouil, Sherry L. Willis, Lennard L. van Wanrooij, Cécile Laubarie-Mouret, Nicolas Lebrun, Pierre Skolil, Francesca Mangiasche, Stéphane Lehéricy, Sophie Guyonnet, Jaana Lindström, Evelyne Cazaban-Campistron, Markku Peltonen, Antti Jula, Juliette Guillemont, Nicola Coley, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institutet [Stockholm], University of Helsinki, Faculty of Health Sciences [UEF, Kuopio, Finland], University of Eastern Finland, Vrije Universiteit Amsterdam [Amsterdam] (VU), Nijmegen Medical Centre [Nijmegen], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), General practice, Public and occupational health, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Aging & Later Life, Graduate School, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CCSD, Accord Elsevier, Department of Public Health, Oral and Maxillofacial Surgery, Department of Medicine, Timo Strandberg / Principal Investigator, and HUS Internal Medicine and Rehabilitation
Subjects: Epidemiology, LIFE-STYLE INTERVENTIONS, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychological intervention, 3124 Neurology and psychiatry, Trial, 0302 clinical medicine, Risk Factors, Outcome Assessment, Health Care, 030212 general & internal medicine, PREDICTORS, Cognitive impairment, Finland, Depression (differential diagnoses), Clinical Trials as Topic, Health Policy, DEPRESSION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cognitive training, Exercise Therapy, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Female, medicine.medical_specialty, DISABILITY FINGER, Physical activity, Intervention, Placebo, EXERCISE ADHERENCE, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Intervention (counseling), Fatty Acids, Omega-3, medicine, Humans, Dementia, OLDER-ADULTS, Life Style, Aged, Cognitive Behavioral Therapy, business.industry, Prevention, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 3112 Neurosciences, COGNITIVE IMPAIRMENT, medicine.disease, Multidomain, FINNISH GERIATRIC INTERVENTION, PHYSICAL-ACTIVITY, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adherence, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Published: 2019

322. Consommation de viandes, poisson, fruits et légumes et risque à long terme de démence ou de maladie d'Alzheimer

Author: Claire Duflos, Catherine Féart, Sylvaine Artero, Laure Ngabirano, Thibault Mura, Cécilia Samieri, Audrey Gabelle, Claudine Berr, 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), 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), Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'Information Médicale [CHRU Montpellier], and The 3C Study is conducted under a partnership agreement between the 'Institut National de la Santé et de la Recherche Médicale' (INSERM), the 'Victor Segalen – Bordeaux II University' and the Sanofi-Synthélabo Company. The 'Fondation pour la Recherche Médicale' funded the study preparation and initiation. The 3C Study is also supported by the 'Caisse Nationale Maladie des Travailleurs Salariés', 'Direction Générale de la Santé', Conseils Régionaux of Aquitaine, Languedoc-Roussillon and Bourgogne, Fondation de France, Ministry of ResearchINSERM Programme ‘Cohortes et collections de données biologiques’, Mutuelle Générale de l’Education Nationale, Institut de la longévité, Conseil Général de la Côte d’Or, Agence Nationale de la Recherche ANR COGINUT (PNRA/200206-01-01) and COGICARE(Longvie 2007LVIE-003-01) and Fonds de coopération scientifique Alzheimer (FCS 2009-2012).
Subjects: 0301 basic medicine, Male, Time Factors, Disease, Cohort Studies, Eating, 0302 clinical medicine, Reverse causation, Risk Factors, Surveys and Questionnaires, Vegetables, Prospective Studies, 2. Zero hunger, Aged, 80 and over, General Neuroscience, Cohort, Fishes, General Medicine, Psychiatry and Mental health, Clinical Psychology, %22">Fish , Female, France, protopathic bias, Meat, reverse causation, 03 medical and health sciences, Alzheimer Disease, Environmental health, medicine, Dementia, Animals, Humans, Aged, fish, business.industry, Proportional hazards model, Feeding Behavior, medicine.disease, Long term risk, 030104 developmental biology, Fruits and vegetables, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Fruit, Geriatrics and Gerontology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: BACKGROUND: The links between diet and the risk of dementia have never been studied considering the possibility of protopathic bias (i.e., reverse causation). OBJECTIVE: We aimed to examine the relationship between consumption frequency of meat, fish, fruits, and vegetables and long-term risk of dementia and Alzheimer's disease (AD), by taking into account this possibility. METHODS: We analyzed data of 5,934 volunteers aged 65 and over from the Three-city study who were followed every 2 to 4 years for 12 years. Dietary habits were assessed at inclusion using a brief food frequency questionnaire. The presence of symptoms of dementia was investigated at each follow-up visit. To limit the risk of protopathic bias, a 4-year lag window between exposure and disease assessment was implemented by excluding from the analyses all dementia cases that occurred during the first four years after inclusion. Analyses were performed using a Cox proportional hazard model and were adjusted for socio-demographic, lifestyle, and health factors. RESULTS: The average follow-up time was 9.8 years. During this period, 662 cases of dementia, including 466 of AD, were identified. After adjustment, only low meat consumption (≤1 time/week) was associated with an increased risk of dementia and AD compared with regular consumption (≥4 times/week) (HR = 1.58 95% CI = [1.17-2.14], HR = 1.67 95% CI = [1.18-2.37], respectively). No association was found between the consumption of fish, raw fruits, or cooked fruits and vegetables and the risk of dementia or AD. CONCLUSION: These findings suggest very low meat consumption increases the long-term risk of dementia and AD, and that a protopathic bias could have impacted finding from previous studies.
Published: 2019

323. Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aß1−42, and Tau Proteins in Elderly Patients With Mild Cognitive Impairment

Author: Emmanuelle Duron, Jean-Sébastien Vidal, Dominique Grousselle, Audrey Gabelle, Sylvain Lehmann, Florence Pasquier, Stéphanie Bombois, Luc Buée, Bernadette Allinquant, Susanna Schraen-Maschke, Christiane Baret, Anne-Sophie Rigaud, Olivier Hanon, Jacques Epelbaum, Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies (EA 4468), Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca, Université Paris Descartes - Paris 5 (UPD5), Groupe hospitalier Broca, Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 de psychiatrie et neurosciences (U894 / UMS 1266), roussel, pascale, Service de neurologie [Saint-Antoine], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, medicine.medical_specialty, Aging, neuropeptide Y, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cognitive Neuroscience, peptides Aß1−42, Neuropeptide, Disease, somatostatin, tau proteins, cerebrospinal fluid, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, mild cognitive impairment, Internal medicine, mental disorders, medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Correction, Neuropeptide Y receptor, 030104 developmental biology, Somatostatin, Endocrinology, Biomarker (medicine), GABAergic, business, 030217 neurology & neurosurgery, peptides Aβ1–42, Neuroscience
Abstract: International audience; A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1–42; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer’s disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1–42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers.Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.
Published: 2019

324. A Clinico-Radiological Study of Cerebral Amyloid Angiopathy-Related Inflammation

Author: Eric Thouvenot, Yassine Boukriche, Nicolas Menjot de Champfleur, Audrey Gabelle, Caroline Arquizan, Claire Duflos, Genevieve Fourcade, Nicolas Raposo, Anne Wacongne, Alain Viguier, Anne Ducros, Laura Chiper, Dimitri Renard, Pierre Labauge, Fabrice Bonneville, Sylvain Lehmann, Mahmoud Charif, Thibaut Allou, Xavier Ayrignac, Sarah Coulette, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Toulouse [Toulouse], Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Hôpital Purpan [Toulouse], Centre Hospitalier Saint Jean de Perpignan, Department of Neurology, Beziers Hospital, Department of Neurology, Narbonne Hospital, 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), Centre d'Etudes Politiques de l'Europe Latine (CEPEL), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Time Factors, Inflammation, 030204 cardiovascular system & hematology, Gastroenterology, Risk Assessment, Lesion, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Recurrence, Risk Factors, Internal medicine, medicine, Humans, Pathological, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Superficial siderosis, 3. Good health, Cerebral Amyloid Angiopathy, Hemiparesis, Diffusion Magnetic Resonance Imaging, Treatment Outcome, Neurology, Radiological weapon, Encephalitis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neurology (clinical), Cerebral amyloid angiopathy, France, medicine.symptom, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Objective: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). Methods: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. Results: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. Conclusion: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.
Published: 2019

325. What is the clinical impact of cerebrospinal fluid biomarkers on final diagnosis and management in patients with mild cognitive impairment in clinical practice? Results from a nation-wide prospective survey in France

Author: Philippe Robert, Jacques Hugon, David Wallon, Bernard Croisile, Alain Jager, Emilie Beaufils, Florence Pasquier, Claire Paquet, Frédéric Blanc, Eloi Magnin, François Mouton Liger, Emmanuelle Duron, Susanna Schraen, Didier Hannequin, Anne-Cécile Troussière, Vincent de la Sayette, Julien Dumurgier, Muriel Quillard, Nathalie Philippi, Carole Miguet-Alfonsi, Audrey Gabelle, Elodie Bouaziz-Amar, Emmanuel Cognat, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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 Lille Nord (France), 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), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe hospitalier Broca, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hospices Civils de Lyon, Departement de Neurologie (HCL), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salvy-Córdoba, Nathalie, Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), 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 de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, medicine.medical_specialty, Databases, Factual, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, Clinical practice, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, Surveys and Questionnaires, medicine, Humans, In patient, Cognitive Dysfunction, 030212 general & internal medicine, Prospective Studies, Stage (cooking), Cognitive impairment, Aged, medicine.diagnostic_test, Lumbar puncture, business.industry, Research, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mild cognitive impairment, General Medicine, Confidence interval, 3. Good health, Clinical Practice, Neurology, Disease Progression, Female, France, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract: ObjectivesNew diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.DesignWe performed a nation-wide, prospective survey between March 2012 and September 2014. Data over the same period was extracted from the French National Database (Banque Nationale Alzheimer, BNA) and compared with the results of the survey.Setting29 secondary and tertiary memory clinics in France.ParticipantsClinicians prescribing lumbar puncture (LP) in order to measure AD CSF biomarkers. Clinicians completed a two-part questionnaire for each of their patients undergoing LP.Primary and secondary outcome measuresAssessment of diagnosis, level of confidence before and after CSF biomarkers and impact on management in patients who underwent LP for CSF AD biomarkers in clinical routine.Results977 questionnaires were completed, of which 61 were excluded because of unknown initial/final diagnosis or non-contributory CSF results. Of 916 patients reported, 153 (16.7%) had MCI as the initial diagnosis, of which 51 (33.3%) displayed an AD profile. CSF biomarkers resulted in a change in diagnosis in 44 patients (28.8%). Confidence level significantly increased after LP (8.3±1.4vs 6.73±1.18, pConclusionThis nation-wide survey, reflecting clinical practice in French memory clinics, describes the impact of CSF AD biomarkers in patients with MCI in clinical practice.
Published: 2019

326. Long-Term Outcomes in Patients with PET-Predicted Poor-Responsive HER2-Positive Breast Cancer Treated with Neoadjuvant Bevacizumab Added to Trastuzumab and Docetaxel: 5-Year Follow-Up of the Randomised AVATAXHER Study

Author: Pierre-Francois Dupre, Marie-Pierre Chauvet, Jean Marc Ferrero, David Coeffic, Jean-Briac Prevost, Thomas Bachelot, Thierry Petit, Alina Berriolo-Riedinger, Catherine Barbe, Julien Dupin, Gilles Paintaud, Kaldoun Kerrou, Philippe Gabelle, Laurent Arnould, Jean-Yves Pierga, Fanny Le Du, Marie-Ange Mouret-Reynier, Bruno Coudert, and Abdennour Ferhat
Subjects: medicine.medical_specialty, Bevacizumab, business.industry, medicine.medical_treatment, medicine.disease, Breast cancer, Docetaxel, Trastuzumab, Internal medicine, medicine, Hormonal therapy, Cumulative incidence, business, Adverse effect, Neoadjuvant therapy, medicine.drug
Abstract: Background: The open-label, randomised Phase 2 AVATAXHER study demonstrated that early PET assessment identified patients with HER-2 positive breast cancer who responded poorly to standard neoadjuvant therapy (docetaxel plus trastuzumab). Adding bevacizumab to neoadjuvant therapy in PET-predicted poor-responders improved pathological complete response (pCR) rates (from 24·0% to 43·8%). We investigated whether the improved pCR rate translated into improved long-term outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with a change in the maximum standardised uptake value (∆SUVmax) ≥70% received four further cycles of standard neoadjuvant therapy (PET responder group). PET-predicted poor-responders (∆SUVmax
Published: 2019

327. Sex-specific depressive symptoms as markers of pre-Alzheimer dementia: findings from the Three- City cohort study

Author: Norton, Joanna, Carrière, Isabelle, Pérès, Karine, Gabelle, Audrey, Berr, Claudine, Ritchie, Karen, Ancelin, Marie-laure, Herrada, Anthony, 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), 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), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), University of Edinburgh, and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Male, Psychiatric Status Rating Scales, Scientific community, Depression, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Article, lcsh:RC321-571, Sex Factors, Alzheimer Disease, Risk Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, Dementia, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Prospective Studies, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biomarkers, Aged
Abstract: International audience; Late-life depression, as a potential marker of pre-dementia, has seldom been explored by symptom dimension and sex, despite sexual dimorphic differences. This study aimed to examine whether specific depressive dimensions were associated with pre-Alzheimer's disease dementia (pre-AD), separately for women and men. Data were drawn from 5617 (58% women) community-dwellers aged 65+ recruited in 1999-2000 and followed at 2-year intervals for 12 years. We used Cox proportional hazard models to study associations between time-dependent Centre for Epidemiologic Studies-Depression Scale (CES-D) symptom dimensions (namely somatic, depressed, positive affect, and interpersonal challenge) and pre-AD, defined retrospectively from validated diagnoses established 3.5 (IQR: 3.2-4.0) years onwards. Analyses were performed according to overall depressive symptomatology (DS+: CES-D score ≥ 16) and antidepressant/anxiolytic medication use (AA). Results indicated that in DS+ women only, all four dimensions were significantly associated with pre-AD in the AA-group, in particular somatic item 'Mind' and depressed affect items 'Depressed' and 'Blues'. The most depression-specific dimension, depressed affect, was also significantly associated with pre-AD in the DS-AA-women (HR:1.28, 95%CI: 1.12;1.47). In both sexes, in the DS-groups somatic affect was the most robust pre-AD marker, irrespective of treatment (women: HR = 1.22, 95%CI: 1.08;1.38; men: HR = 1.30, 95%CI: 1.14;1.48). Our findings highlight sex-specific associations between depressive symptom dimensions and pre-AD, modulated by depressive symptomatology and treatment. Assessment of specific symptom dimensions taking into account overall symptomatology and treatment could help identify and target high-risk AD-dementia profiles for interventions.
Published: 2019

328. Generation of induced pluripotent stem cells (iPSCs) IRMBi002-A from an Alzheimer's disease patient carrying a D694N mutation in the APP gene

Author: V. Cacheux, L. Auboyer, C. Monzo, I. Gazagne, David Wallon, Audrey Gabelle, Sylvain Lehmann, Anne Rovelet-Lecrux, Carole Crozet, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), 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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Heterozygote, Cellular differentiation, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Germ layer, medicine.disease_cause, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, Alzheimer Disease, Amyloid precursor protein, medicine, Humans, Induced pluripotent stem cell, lcsh:QH301-705.5, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Mutation, biology, Cell Differentiation, Cell Biology, General Medicine, Fibroblasts, Middle Aged, biology.organism_classification, Cellular Reprogramming, Phenotype, Sendai virus, In vitro, 3. Good health, lcsh:Biology (General), Cancer research, biology.protein, Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 58 year-old woman suffering from Alzheimer's disease and carrying a D694N mutation on Amyloid precursor protein (APP). Fibroblasts were reprogrammed into iPSC using the integration-free Sendai Virus which allows the expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers. The cells have the corresponding mutation and present a normal karyotype. The reported APP-D694N iPSC line may be used to model and study human AD pathology in vitro.
Published: 2019

329. Intake of meat, fish, fruits and vegetables and long-term risk of dementia and Alzheimer's disease

Author: Ngabirano, Laure, Samieri, Cecilia, Feart, Catherine, Gabelle, Audrey, Artero, Sylvaine, Duflos, Claire, Berr, Claudine, Mura, Thibaut, Berr, Claudine, 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), 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), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'Information Médicale [CHRU Montpellier], and The 3C Study is conducted under a partnership agreement between the 'Institut National de la Santé et de la Recherche Médicale' (INSERM), the 'Victor Segalen – Bordeaux II University' and the Sanofi-Synthélabo Company. The 'Fondation pour la Recherche Médicale' funded the study preparation and initiation. The 3C Study is also supported by the 'Caisse Nationale Maladie des Travailleurs Salariés', 'Direction Générale de la Santé', Conseils Régionaux of Aquitaine, Languedoc-Roussillon and Bourgogne, Fondation de France, Ministry of ResearchINSERM Programme ‘Cohortes et collections de données biologiques’, Mutuelle Générale de l’Education Nationale, Institut de la longévité, Conseil Général de la Côte d’Or, Agence Nationale de la Recherche ANR COGINUT (PNRA/200206-01-01) and COGICARE(Longvie 2007LVIE-003-01) and Fonds de coopération scientifique Alzheimer (FCS 2009-2012).
Subjects: fish, meat, protopathic bias, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, reverse causation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, dementia
Abstract: International audience; BACKGROUND:The links between diet and the risk of dementia have never been studied considering the possibility of protopathic bias (i.e., reverse causation).OBJECTIVE:We aimed to examine the relationship between consumption frequency of meat, fish, fruits, and vegetables and long-term risk of dementia and Alzheimer's disease (AD), by taking into account this possibility.METHODS:We analyzed data of 5,934 volunteers aged 65 and over from the Three-city study who were followed every 2 to 4 years for 12 years. Dietary habits were assessed at inclusion using a brief food frequency questionnaire. The presence of symptoms of dementia was investigated at each follow-up visit. To limit the risk of protopathic bias, a 4-year lag window between exposure and disease assessment was implemented by excluding from the analyses all dementia cases that occurred during the first four years after inclusion. Analyses were performed using a Cox proportional hazard model and were adjusted for socio-demographic, lifestyle, and health factors.RESULTS:The average follow-up time was 9.8 years. During this period, 662 cases of dementia, including 466 of AD, were identified. After adjustment, only low meat consumption (≤1 time/week) was associated with an increased risk of dementia and AD compared with regular consumption (≥4 times/week) (HR = 1.58 95% CI = [1.17-2.14], HR = 1.67 95% CI = [1.18-2.37], respectively). No association was found between the consumption of fish, raw fruits, or cooked fruits and vegetables and the risk of dementia or AD.CONCLUSION:These findings suggest very low meat consumption increases the long-term risk of dementia and AD, and that a protopathic bias could have impacted finding from previous studies.
Published: 2019

330. Absence of Relationship Between Self-Reported Sleep Measures and Amyloid Load in Elderly Subjects

Author: Audrey Gabelle, Laure-Anne Gutierrez, Isabelle Jaussent, Fayçal Ben Bouallegue, Delphine De Verbizier, Sophie Navucet, Caroline Grasselli, Karim Bennys, Cécilia Marelli, Renaud David, Denis Mariano-Goulart, Sandrine Andrieu, Bruno Vellas, Pierre Payoux, Claudine Berr, Yves Dauvilliers, MORNET, Dominique, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [Montpellier], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), 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), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, cognition, medicine.medical_specialty, [SDV]Life Sciences [q-bio], NAPS, Logistic regression, elderly, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Insomnia, Dementia, sleep, lcsh:Neurology. Diseases of the nervous system, ComputingMilieux_MISCELLANEOUS, Original Research, amyloidosis, PET—positron emission tomography, business.industry, Amyloidosis, Neuropsychology, Apnea, Sleep apnea, amyloid, medicine.disease, Sleep in non-human animals, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, dementia
Abstract: Objective: To determine the relationships between self-reported sleep profile and cortical amyloid load in elderly subjects without dementia.Methods: This cross-sectional study included 143 community-dwelling participants aged ≥70 years (median: 73 years [70–85]; 87 females) with spontaneous memory complaints but dementia-free. Sociodemographic characteristics, health status, neuropsychological tests, sleep, and 18F-florbetapir (amyloid) PET data were collected. The clinical sleep interview evaluated nighttime sleep duration, but also daytime sleep duration, presence of naps, and restless leg syndrome (RLS) at time of study. Validated questionnaires assessed daytime sleepiness, insomnia, and risk of sleep apnea. The cortical standardized uptake value ratio (SUVr) was computed across six cortical regions. The relationship between sleep parameters and SUVr (cut-off ratio>1.17 and tertiles) was analyzed using logistic regression models.Results: Amyloid-PET was positive in 40.6% of participants. Almost 40% were at risk for apnea, 13.5% had RLS, 35.5% insomnia symptoms, 22.1% daytime sleepiness, and 18.8% took sleep drugs. No significant relationship was found between positive amyloid PET and nighttime sleep duration (as a continuous variable, or categorized into
Published: 2019

331. Reduced brain amyloid burden in elderly patients with narcolepsy type 1

Author: Audrey, Gabelle, Isabelle, Jaussent, Fayçal Ben, Bouallègue, Sylvain, Lehmann, Régis, Lopez, Lucie, Barateau, Caroline, Grasselli, Carole, Pesenti, Delphine, de Verbizier, Séverine, Béziat, Denis, Mariano-Goulart, Bertrand, Carlander, Yves, Dauvilliers, Nicola, Coley, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Unité des troubles du sommeil et de l’éveil [Montpellier], Gui de Chauliac - CHRU de Montpellier, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Sleep disorders center, Hôpital Gui-de-Chauliac, Service de médecine nucléaire [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and MORNET, Dominique
Subjects: Aged, 80 and over, Male, Amyloid beta-Peptides, amyloid-PET, [SDV]Life Sciences [q-bio], Brain, amyloid, biomarkers, Plaque, Amyloid, narcolepsy, [SDV] Life Sciences [q-bio], orexin, Alzheimer Disease, Positron-Emission Tomography, Alzheimer, Humans, Female, sleep, ComputingMilieux_MISCELLANEOUS, Aged
Abstract: To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile.Cognitive andLower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p 0.0001], and 1.14 ± 0.17 [p = 0.0005], respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only 1 patient with NT1 (4.4%) had positive PET amyloid compared with 27.5% in the ADNI and 30.4% in the MAPT-AV45 group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers, or neuropsychological profile.Lower brain amyloid burden, assessed by
Published: 2019

332. The Relationship between Narcissism, Worker Relations, and Social Media Use Among Telecommunication Company's Employees in Laguna

Author: Danyael Dedeles and Gabelle Baniqued
Published: 2019
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333. Stable Isotope Labeling Kinetics in CNS Translational Medicine: Introduction to SILK Technology

Author: Paul T. Kotzbauer, Timothy M. Miller, Kevin E. Yarasheski, Tim West, Katrina L. Paumier, Audrey Gabelle, Randall J. Bateman, Sylvain Lehmann, Christophe Hirtz, John R. Cirrito, Chihiro Sato, Nicolas R. Barthélemy, Brendan P. Lucey, Bruce W. Patterson, and James G. Bollinger
Subjects: Apolipoprotein E, Amyloid, biology, Amyloid beta, business.industry, SOD1, Disease, medicine.disease, Drug development, medicine, biology.protein, Dementia, Amyotrophic lateral sclerosis, business, Neuroscience
Abstract: Alzheimer's disease (AD) is the most common cause of dementia, and it is currently estimated to afflict 5 million people in the United States. Several therapeutic targets have been identified as contributors to Alzheimer's disease pathophysiology such as Aβ, tau, inflammation, and other disease-causing mechanisms, but highly effective therapies and accurate diagnostic tests are still currently unavailable. Most current therapeutic approaches target Aβ, and the treatment of Alzheimer's disease is often initiated during the mild-to-moderate stage of dementia, which may be too late as 50% of hippocampal neurons are typically dead at this point. Initially, in order to understand Aβ kinetics in the pathophysiology of Alzheimer's disease, we developed a novel method to metabolically label central nervous system (CNS) proteins during protein translation and sample labeled proteins from cerebrospinal fluid (CSF) during and after labeling to measure the kinetics of proteins in the CNS. We have utilized this technique of stable isotope labeling kinetics (SILK) to successfully measure the production and clearance of Aβ in the human CNS and have since translated this approach to other model systems including in vitro cell culture and animal models and to other proteins and diseases such as apolipoprotein E, soluble amyloid precursor proteins, tau, superoxide dismutase-1 (SOD1) in amyotrophic lateral sclerosis, and alpha-synuclein in Parkinson's disease. This chapter will review recent advancements in the development and application of SILK for measuring the pathophysiology and drug development for CNS diseases. SILK has provided important insights into Alzheimer's disease pathophysiology with altered synthesis and clearance of amyloid-beta, and drug effects on amyloid-beta. Further, the risk factors of AD, including aging, the largest AD risk factor, reveal profound slowing of amyloid-beta clearance, and the most prevalent genetic risk factor, apolipoprotein E, is being assessed. The initial work in AD has been expanded to specific proteins involved in the pathogenesis of other CNS disorders including amyotrophic lateral sclerosis (i.e., SOD) and Parkinson's disease (i.e., alpha-synuclein). The use of SILK technology with specific disease-causing proteins has been generalized using SILAV to expand its application to addressing questions in proteomics and the peripheral compartments outside of the CNS.
Published: 2019

334. Generation of induced pluripotent stem cells (IRMBi001-A) from an Alzheimer's disease patient carrying a G217D mutation in the PSEN1 gene

Author: Sylvain Lehmann, Audrey Gabelle, Anne Rovelet-Lecrux, David Wallon, V. Cacheux, L. Auboyer, Carole Crozet, C. Monzo, I. Gazagne, 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), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), 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 Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Salvy-Córdoba, Nathalie, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Male, Induced Pluripotent Stem Cells, Cell Culture Techniques, Germ layer, Biology, medicine.disease_cause, Presenilin, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Alzheimer Disease, PSEN1, medicine, Presenilin-1, Animals, Humans, Induced pluripotent stem cell, lcsh:QH301-705.5, Mutation, Base Sequence, MESH: Alzheimer Disease / pathology, Cell Culture Techniques / methods, Induced Pluripotent Stem Cells / pathology, Mutation / genetics, Presinilin-1 / genetics, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Cell Biology, General Medicine, Middle Aged, biology.organism_classification, Sendai virus, 030104 developmental biology, lcsh:Biology (General), Cell culture, Cancer research, Reprogramming, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 50 year-old patient suffering from Alzheimer's disease and carrying a G217D causal mutation on presenilin 1 (PSEN1). iPSCs were obtained following reprogramming using the integration-free Sendai Virus system which allows expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers. iPS cells carry the patient G217D mutation and present a normal karyotype. The reported PS1-G217D iPSC line may be used to model and study human AD pathology in vitro.
Published: 2019

335. Age Modifies the Association Between Apolipoprotein E Genotype and Alzheimer's Disease: A CSF Biomarker-Based Multicentric Case-Control Study

Author: Aurore Fayosse, Lucilla Parnetti, Jacques Hugon, Inga Zerr, Jean-Louis Laplanche, Audrey Gabelle, Alzheimer’s Disease Neuroimaging Initiative, Sebastiaan Engelborghs, Elodie Bouaziz-Amar, Christine Van Broeckhoven, Aline Dugravot, Julien Dumurgier, Archana Singh-Manoux, Maria Bjerke, Nicola Salvadori, Hana Sadikki, Kaj Blennow, Claire Paquet, Adelina Orellana, Timo Grimmer, Lucia Farotti, Sylvain Lehmann, David Wallon, Peter Hermann, Mercè Boada, Matthieu Lilamand, Itziar de Rojas, Christopher Tzourio, Claire Hourregue, Panagiotis Alexopoulos, Emmanuel Cognat, Gaël Nicolas, Séverine Sabia, Henrik Zetterberg, and Janine Diehl-Schmid
Subjects: Apolipoprotein E, medicine.medical_specialty, education.field_of_study, business.industry, Population, Case-control study, Disease, Odds ratio, medicine.disease, 3. Good health, Internal medicine, Attributable risk, medicine, Biomarker (medicine), Dementia, education, business
Abstract: Background: We investigated the global and age-specific association between Apolipoprotein E (APOE) genotype and Alzheimer's disease (AD) in a large multicentric case-control study, using cerebrospinal fluid (CSF) biomarkers-based diagnostic criteria for AD. Methods: In this case-control design, data on 1,599 Caucasian AD cases with abnormal values of CSF biomarkers came from 9 European memory clinics and the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. AD cases were compared to 11,724 dementia-free controls, drawn from two longitudinal cohort studies (Whitehall II and 3-City). Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were reported, overall and by 5-year age categories. Findings. 63*4% of CSF biomarker-defined AD patients and 22*6% of population controls carried at least one APOE e4 allele; respective percentages for APOE e4 homozygotes were 16*7% and 1*4%. Compared to none4 carriers, heterozygous e4 carriers had a 4*6 (95% confidence interval: 4*1 - 5*2) and e4/e4 homozygotes a 25*4 (20*5 - 31*3) higher OR of AD. This association was strongly modified by age (p for interaction < 0*001). The PAF associated with carrying at least one e4 allele was greatest in the 65-70 age group (69*7%), and weaker before 55 years (14*2%) and after 85 years (22*6%). There was some evidence of a stronger effect of APOE on AD risk in women. Interpretation: Incorporating biomarkers for diagnosis of AD led to a stronger association with APOE e4 than previously reported, perhaps due to better diagnostic accuracy. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE e4 at the population level. Funding Statement: US National Institutes of Health, Fondation Plan Alzheimer. Declaration of Interests: ASM is supported by NIH/NIA R01AG056477. IZ is supported by the Robert-Koch-Institute through funds of Federal Ministry of Health (grant no. 1369-341) and DZNE (German Center for Neurodegenerative Diseases). KB reports consulting fees from Fujirebio Europe, IBL International, Roche Diagnostics. HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. MB has been a consultant for Araclon, Avid, Bayer, Elan, Grifols, Janssen/Pfizer, Lilly, Neuroptix, Nutricia, Roche, Sanofi, and Servier. All other authors declare no competing interests. Ethics Approval Statement: Ethical clearance was obtained by the institutional review boards of all participating sites (European memory centers and ADNI Study sites) and all participants provided written, informed consent.
Published: 2019

336. Additional file 1: of The prognostic value of the Tau protein serum level in metastatic breast cancer patients and its correlation with brain metastases

Author: Darlix, Amélie, Hirtz, Christophe, Thezenas, Simon, Maceski, Aleksandra, Gabelle, Audrey, Lopez-Crapez, Evelyne, Forges, Hélène, Firmin, Nelly, Guiu, Séverine, Jacot, William, and Lehmann, Sylvain
Abstract: Table S1. Patients’ clinical and biological characteristics. Table S2. Characteristics of brain metastases. Table S3. Univariate analysis of OS (A) in the whole MBC population (n = 244) and (B) in the BM population (n = 86): additional results. (DOCX 75 kb)
Published: 2019
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337. Dementia risk‐stratification in a large, decentralized cohort of aging individuals with subjective cognitive complaints from the INTUITION brain health study.

Author: Gabelle, Audrey, Butler, P. Monroe, Saha‐Chaudhuri, Paramita, Brown, Roland, Hobbs, Matt, Becker, Andrew, Bianchi, Matt, Lenyoun, Hanson, Hughes, Richard, and Belachew, Shibeshih
Abstract: Background: Subjective cognitive complaints (SCC) signal risk of objective cognitive decline. To better understand the bio‐behavioral factors that signal cognitive trajectories at‐risk for the earliest stages of Alzheimer' disease, there is a need for well‐phenotyped large‐scale population‐based cohorts with longitudinal assessments. Method: From the INTUITION decentralized observational brain health study (NCT0505895), using app‐collected self‐report data, we compared the demographic, clinical, and neuropsychological profiles of 2045 SCC versus 4090 age‐ and education‐matched cognitively normal (CN) participants. The SCC cohort was defined by age (> = 50 years) and presence of significant cognitive concerns based on total scores> = 4 on the 14‐item Cognitive Function Instrument (CFI‐14). Using customized assessments from Cambridge Cognition, Pattern Recognition Memory (PRM), Paired Associates Learning (PAL), Spatial Working Memory (SWM), and Match‐to‐Sample (MTS) tests were performed. SCC participants were stratified and compared by presence or absence of dementia risk factors (first‐degree family history of dementia (FH+/FH‐) or 2+ cardiovascular risk factors (CVRF2+/CVRF2‐)). Result: Cognitive and neuropsychiatric symptom‐burden were greater among the SCC cohort compared to CN participants (e.g., E‐Cog‐12: 1.8(0.5) vs 1.2(0.3), pathological PHQ2 (Total> = 3): 14% vs 2.7%, pathological GAD‐2(Total> = 3): 11.8% vs 1.9%, respectively p<0.001). Lifestyle factors differed, with SCC participants reporting lower level of physical activity, higher substance use and impaired sleep, relative to CN. Among SCC participants the prevalence of CVRF2+ and FH+ were 53.2% and 37.8%, respectively; and 43% (CVRF2+) and 33.5% (FH+) among CN. Among SCC, individuals with CVRF2+ were more likely to be older, male, and with higher rates of anxiety/depression symptoms. Mean total CFI‐14 scores were similar between FH+/FH‐ or CVRF2+/CVRF2‐, but item‐level CFI profiles differed (e.g., word‐finding complaints in FH+/CVRF2+). SCC scored lower on key CANTAB outcomes (e.g., PAL/PRM) evaluated compared to CN. Both CVRF2+ and FH+ participants with SCC performed worse on cognitive measures of learning (SWM) and attention (MTS) compared to CVRF2‐ and FH‐ respectively. Conclusion: In a large, decentralized cohort, SCC was associated with higher burden of modifiable and non‐modifiable risk factors. First‐degree family history of dementia and cardiovascular disease, when coupled with SCC, revealed more severe measurable objective cognitive deficits. Future work will assess individual longitudinal cognitive trajectories. [ABSTRACT FROM AUTHOR]
Published: 2023
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338. Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia

Author: Le Ber, Isabelle, Guedj, Eric, Gabelle, Audrey, Verpillat, Patrice, Volteau, Magali, Thomas-Anterion, Catherine, Decousus, Marielle, Hannequin, Didier, Véra, Pierre, Lacomblez, Lucette, Camuzat, Agnès, Didic, Mira, Puel, Michèle, Lotterie, Jean-Albert, Golfier, Véronique, Bernard, Anne-Marie, Vercelletto, Martine, Magne, Christine, Sellal, François, Namer, Izzie, Michel, Bernard-François, Pasquier, Jacques, Salachas, François, Bochet, Jean, Brice, Alexis, Habert, Marie-Odile, and Dubois, Bruno
Published: 2006

339. Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial.

Author: Houvenaeghel, Gilles, Cohen, Monique, Raro, Pédro, De Troyer, Jérémy, Gimbergues, Pierre, Tunon de Lara, Christine, Ceccato, Vivien, Vaini-Cowen, Véronique, Faure-Virelizier, Christelle, Marchal, Frédéric, Gauthier, Tristan, Jouve, Eva, Theret, Pierrick, Regis, Claudia, Gabelle, Philippe, Pernaut, Julia, Del Piano, Francesco, D'Halluin, Gauthier, Lantheaume, Stéphane, and Darai, Emile
Published: 2021
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340. Socioeconomic inequalities in dementia risk among a French population-based cohort: quantifying the role of cardiovascular health and vascular events.

Author: Letellier, Noémie, Ilango, Sindana D., Mortamais, Marion, Tzourio, Christophe, Gabelle, Audrey, Empana, Jean-Philippe, Samieri, Cécilia, Berr, Claudine, and Benmarhnia, Tarik
Subjects: DISEASE risk factors, STATISTICAL models, SOCIOECONOMIC status, DEMENTIA, DIAGNOSIS
Abstract: This study aimed to investigate the role of cardiovascular health (CVH) and vascular events as potential contributors to socioeconomic inequalities in dementia using causal mediation analyses. We used data from the Three-City Cohort, a French population-based study with 12 years of follow-up, with active search of dementia cases and validated diagnosis. Individual socioeconomic status was assessed using education, occupation and income. A CVH score as defined by the American Heart Association and incident vascular events were considered separately as mediators. We performed multi-level Cox proportional and Aalen additive hazard regression models to estimate the total effects of socioeconomic status on dementia risk. To estimate natural direct and indirect effects through CVH and vascular events, we applied two distinct weighting methods to quantify the role of CVH and vascular events: Inverse Odds Ratio Weighting (IORW) and Marginal Structural Models (MSM) respectively. Among 5581 participants, the risk of dementia was higher among participants with primary education (HR 1.60, 95%CI 1.44–1.78), blue-collar workers (HR 1.62, 95%CI 1.43–1.84) and with lower income (HR 1.23, 95%CI 1.09–1.29). Using additive models, 571 (95% CI 288–782) and 634 (95% CI 246–1020) additional cases of dementia per 100 000 person and year were estimated for primary education and blue-collar occupation, respectively. Using IORW, the CVH score mediate the relationship between education or income, and dementia (proportion mediated 17% and 26%, respectively). Yet, considering vascular events as mediator, MSM generated indirect effects that were smaller and more imprecise. Socioeconomic inequalities in dementia risk were observed but marginally explained by CVH or vascular events mediators. [ABSTRACT FROM AUTHOR]
Published: 2021
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341. Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.

Author: Chamberlain, Jonviea D., Rouanet, Anaïs, Dubois, Bruno, Pasquier, Florence, Hanon, Olivier, Gabelle, Audrey, Ceccaldi, Mathieu, Krolak‐Salmon, Pierre, Béjot, Yannick, Godefroy, Olivier, Wallon, David, Gentric, Armelle, Chêne, Geneviève, and Dufouil, Carole
Abstract: Introduction: Studies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding. Methods: This 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. Results: The 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). Discussion: This study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms. [ABSTRACT FROM AUTHOR]
Published: 2021
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342. THE INFLUENCE OF ACTIVITY SPACE ON THE ASSOCIATION BETWEEN NEIGHBORHOOD CHARACTERISTICS AND DEMENTIA

Author: Letellier, Noemie, Carriere, Isabelle, Gutierrez, Laure Anne, Gabelle, Audrey, Dartigues, Jean-François, Dufouil, Carole, Helmer, Catherine, Cadot, Emmanuelle, and Berr, Claudine
Published: 2018
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343. Primary Progressive Aphasia in the Network of French Alzheimer Plan Memory Centers

Author: Magnin, Eloi, Démonet, Jean-François, Wallon, David, Dumurgier, Julien, Troussière, Anne-Cécile, Jager, Alain, Duron, Emmanuelle, Gabelle, Audrey, de La Sayette, Vincent, Volpe-Gillot, Lisette, Tio, Gregory, Evain, Sarah, Boutoleau-Bretonnière, Claire, Enderle, Adeline, Mouton-Liger, François, Robert, Philippe, Hannequin, Didier, Pasquier, Florence, Hugon, Jacques, Paquet, Claire, Collaborators, Eplm, 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], 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), Centre Mémoire de Ressources et de Recherche Paris Nord Ile-de-France (CMRR), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Mémoire de Ressources et de Recherche - CMRR [CHRU Lille], Centre de Neurologie [Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre de Mémoire de Ressources et de Recherche [Paris Broca], AP-HP - Hôpital Broca [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe Hospitalier Paris Saint Joseph, Centre Mémoire de Ressources et de Recherche [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Cognition Behaviour Technology (CobTek), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)
Subjects: Male, 0301 basic medicine, Databases, Factual, Disease, frontotemporal dementia, Cohort Studies, Tertiary Care Centers, Primary progressive aphasia, 0302 clinical medicine, Epidemiology, gender, Medicine, Prospective Studies, Prospective cohort study, Cognitive reserve, Aged, 80 and over, education.field_of_study, General Neuroscience, General Medicine, Middle Aged, respiratory system, 3. Good health, Psychiatry and Mental health, Clinical Psychology, epidemiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, France, Alzheimer’s disease, Cognitive psychology, Frontotemporal dementia, medicine.medical_specialty, Population, 03 medical and health sciences, Alzheimer Disease, Internal medicine, Humans, cerebrospinal fluid biomarkers, education, Secondary Care Centers, Aged, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, Aphasia, Primary Progressive, 030104 developmental biology, primary progressive aphasia, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Few demographical data about primary progressive aphasia (PPA) are available, and most knowledge regarding PPA is based on tertiary centers' results. OBJECTIVE: Our aims were to describe demographical characteristics of the PPA population in a large sample of PPA patients from the network of French Alzheimer plan memory centers (Sample 1), and to describe the stratification of cerebrospinal fluid (CSF) biomarkers in two different samples of PPA patients (Samples 2 and 3). METHODS: All registered PPA patients in the French Alzheimer's disease (AD) databank (Sample 1: n = 2,035) and a subsample (Sample 2: n = 65) derived from a multicentric prospective cohort with CSF biomarker analysis were analyzed. A multicentric retrospective cohort from language expert tertiary centers (Sample 3: n = 97) with CSF biomarker analysis was added. Sample 3 was added to replicate the CSF results of the Sample 2 and to evaluate repartition of AD pathology in the three variant of PPA according to the latest classification. RESULTS: Non-Fluent/Agrammatic, Logopenic, and Unclassifiable PPA patients (NF/A-Logo-Unclass PPA) were older and more frequent than Semantic PPA patients (2.2 versus 0.8/100,000 inhabitants; p
Published: 2016

344. Cerebrospinal Fluid Alzheimer’s Disease Biomarkers in Cerebral Amyloid Angiopathy-Related Inflammation

Author: Anne Le Floch, Dimitri Renard, Souhayla Azakri, Xavier Ayrignac, Sylvain Lehmann, Cecilia Marelli, Christophe Hirtz, Eric Thouvenot, Anne Wacongne, Mahmoud Charif, Stephane Bouly, Audrey Gabelle, Caroline Arquizan, Genevieve Fourcade, Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Plateforme de Protéomique Clinique, CHU Saint-Eloi, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pathology, [SDV]Life Sciences [q-bio], tau Proteins, Inflammation, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, In patient, cardiovascular diseases, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Amyloid beta-Peptides, business.industry, General Neuroscience, nutritional and metabolic diseases, Alzheimer's disease biomarkers, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, 3. Good health, Cerebral Amyloid Angiopathy, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Csf biomarkers, Female, Cerebral amyloid angiopathy, Geriatrics and Gerontology, medicine.symptom, Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Research Article
Abstract: BACKGROUND Decreased cerebrospinal fluid (CSF) amyloid-β 1-40 (Aβ40) and amyloid-β 1-42 (Aβ42) and increased total and phosphorylated tau (t-tau, p-tau) concentrations have been described in cerebral amyloid angiopathy (CAA). OBJECTIVE Our aim was to analyze these biomarkers in patients with CAA-related inflammation (CAA-I). METHODS We prospectively recruited nine patients with acute phase CAA-I fulfilling Chung criteria. CSF was analyzed for t-tau, p-tau, Aβ42, and Aβ40. Data were compared to controls (n = 14), patients with Alzheimer's disease (AD, n = 42), CAA (n = 10), and primary angiitis of the central nervous system (PACNS, n = 3). RESULTS For the CAA-I group, statistically significant differences were: lower Aβ42 (p = 0.00053) compared to the control group; lower t-tau (p = 0.018), p-tau (p < 0.001), and Aβ40 (p < 0.001) compared to AD; lower Aβ42 (p = 0.027) compared to CAA; lower Aβ42 (p = 0.012) compared to PACNS. Nearly significantly lower Aβ40 (p = 0.051) and higher t-tau (p = 0.051) were seen in CAA-I compared to controls. CONCLUSION CSF biomarkers profile similar to that of CAA was observed in CAA-I (with even lower levels of Aβ42 compared to CAA). Based on our findings, high p-tau seems more specific for AD, whereas low Aβ42 differentiates CAA-I from CAA, PACNS, and controls, and low Aβ40 differentiates CAA-I from AD.
Published: 2016

345. Prise en charge des lésions exophytiques condylomateuses pendant la grossesse par vaporisation laser au CO 2

Author: Gay, C, Terzibachian, J.J, Gabelle, C, Reviron, S, Ramanah, R, and Mougin, C
Published: 2003
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346. Que deviennent nos vieux hyperactifs ? Le trouble déficit de l’attention/hyperactivité chez la personne âgée

Author: Yves Dauvilliers, Régis Lopez, L. Camodeca, Jean-Arthur Micoulaud-Franchi, and Audrey Gabelle
Subjects: Psychiatry and Mental health, Neurology (clinical), Geriatrics and Gerontology
Abstract: Resume Le trouble deficit de l’attention/hyperactivite (TDA/H) est un trouble neurodeveloppemental qui debute dans l’enfance et persiste souvent a l’âge adulte. Peu de donnees sont disponibles sur l’evolution du trouble avec l’âge. La possibilite de la persistance du TDA/H avec le grand âge emerge depuis quelques annees avec quelques etudes sur la prevalence, les caracteristiques cliniques, les comorbidites et le retentissement du TDA/H dans cette population. Les objectifs de cette revue de la litterature sont de decrire l’evolution du TDA/H avec l’âge chez l’adulte, de rapporter les resultats des premieres etudes sur le TDA/H chez la personne âgee et discuter des possibles liens entre le TDA/H et les troubles cognitifs lies a l’âge.
Published: 2015

347. 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

348. HIV Neuroinfection and Alzheimer’s Disease: Similarities and Potential Links?

Author: Geoffrey Canet, Chloé Dias, Audrey Gabelle, Yannick Simonin, Fabien Gosselet, Nicola Marchi, Alain Makinson, Edouard Tuaillon, Philippe Van de Perre, Laurent Givalois, Sara Salinas, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département des Maladies Infectieuses [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Boutin, Marion, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), École Pratique des Hautes Études (EPHE), and Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI)
Subjects: 0301 basic medicine, Amyloid, [SDV]Life Sciences [q-bio], Inflammation, Disease, Blood–brain barrier, lcsh:RC321-571, neuroinflammation, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, HIV-associated neurocognitive disorders, medicine, Dementia, hypothalamo-pituitary-adrenal axis, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Neuroinflammation, ComputingMilieux_MISCELLANEOUS, business.industry, Neurodegeneration, viral neuroinfection, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, medicine.symptom, business, Neuroscience, Neurocognitive, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: International audience; Environmental factors such as chemicals, stress and pathogens are now widely believed to play important roles in the onset of some brain diseases, as they are associated with neuronal impairment and acute or chronic inflammation. Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neurodegeneration that ultimately lead to dementia. Neuroinflammation also plays a prominent role in AD and possible links to viruses have been proposed. In particular, the human immunodeficiency virus (HIV) can pass the blood-brain barrier and cause neuronal dysfunction leading to cognitive dysfunctions called HIV-associated neurocognitive disorders (HAND). Similarities between HAND and HIV exist as numerous factors involved in AD such as members of the amyloid and Tau pathways, as well as stress-related pathways or blood brain barrier (BBB) regulators, seem to be modulated by HIV brain infection, leading to the accumulation of amyloid plaques or neurofibrillary tangles (NFT) in some patients. Here, we summarize findings regarding how HIV and some of its proteins such as Tat and gp120 modulate signaling and cellular pathways also impaired in AD, suggesting similarities and convergences of these two pathologies.
Published: 2018

349. Alzheimer's Disease: Advances in Drug Development

Author: Anne Dominique Lajoix, Sylvain Lehmann, Caroline Desmetz, Christophe Hirtz, Morgane Piton, Karim Bennys, Jacqueline Milhau, Audrey Gabelle, Biocommunication en Cardio-Métabolique (BC2M), Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, early onset, Disease, tau proteins, amyloid-β peptides, Neuron loss, cell- and tissue-based therapy, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Alzheimer Disease, Humans, Medicine, Senile plaques, Cognitive impairment, business.industry, General Neuroscience, amyloid-β protein precursor secretases, Cognition, General Medicine, 3. Good health, Clinical trial, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Drug development, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, immunotherapy, Geriatrics and Gerontology, Neurodegenerative dementia, business, Neuroscience, Alzheimer’s disease, 030217 neurology & neurosurgery, genetic therapy, Antipsychotic Agents
Abstract: International audience; As of 2018, Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. It contributes to a progressive neuron loss, deterioration of memory, and cognitive impairment. Current therapies may provide a symptomatic benefit, but do not treat the underlying process. Ongoing researches focus on understanding the causal mechanisms and finding neuropathological hallmarks of AD. Therapeutic approaches targeting senile plaques or neurofibrillary tangles have not yet resulted in a significant cognitive improvement. However, recent data according to the analysis of AD clinical trials (clinicaltrials.gov database) show promising results. This literature review aims at summarizing the recent advances and at highlighting the most promising results of the ongoing researches. It compares the merits of small-molecules, antibodies, cell, and gene-based therapies and emphasizes the need for treatment at earlier stages of the disease.
Published: 2018

350. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer's disease and vascular dementia

Author: Rémy Umoret, Jeffrey M. Sequeira, Edward V. Quadros, Jean-Louis Guéant, Jean-Michel Camadro, Valérie Rigau, Sylvain Lehmann, Carine Bossenmeyer-Pourié, Bernard Sablonnière, A. David Smith, Déborah Helle, Jean-Luc Daval, Racha Kerek, Rosa-Maria Guéant-Rodriguez, Vincent Deramecourt, Audrey Gabelle, Grégory Pourié, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Biologie-Pathologie, UF de Neurobiologie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), SUNY Downstate Medical Center, State University of New York (SUNY), IMPACT GEENAGE, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Oxford [Oxford], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), and Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille]
Subjects: 0301 basic medicine, medicine.medical_specialty, Hyperhomocysteinemia, Aging, Homocysteine, Normal diet, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, tau Proteins, folate, Pathology and Forensic Medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Animals, Humans, Cognitive Dysfunction, Vitamin B12, tau, Cognitive decline, Vascular dementia, Mice, Knockout, Alzheimer-type dementia, business.industry, Dementia, Vascular, microtubule-associated proteins, Brain, homocysteine, vitamin B12, medicine.disease, 3. Good health, Rats, 030104 developmental biology, Endocrinology, chemistry, Ageing, 030220 oncology & carcinogenesis, Female, Autopsy, business
Abstract: International audience; The pathomechanisms that associate a deficit in folate and/or vitamin B12 and the subsequent hyperhomocysteinemia with pathological brain ageing are unclear. We investigated the homocysteinylation of microtubule-associated proteins (MAPs) in brains of patients with Alzheimer's disease or vascular dementia, and in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency and H19-7 neuroprogenitors lacking folate. Compared with controls, N-homocysteinylated tau and MAP1 were increased and accumulated in protein aggregates and tangles in the cortex, hippocampus and cerebellum of patients and animals. N-homocysteinylation dissociated tau and MAPs from β-tubulin, and MS analysis showed that it targets lysine residues critical for their binding to β-tubulin. N-homocysteinylation increased in rats exposed to vitamin B12 and folate deficit during gestation and lactation and remained significantly higher when they became 450 days-old, despite returning to normal diet at weaning, compared with controls. It was correlated with plasma homocysteine (Hcy) and brain expression of methionine tRNAsynthetase (MARS), the enzyme required for the synthesis of Hcy-thiolactone, the substrate of N-homocysteinylation. Experimental inactivation of MARS prevented the N-homocysteinylation of tau and MAP1, and the dissociation of tau and MAP1 from β-tubulin and PSD95 in cultured neuroprogenitors. In conclusion, increased N-homocysteinylation of tau and MAP1 is a mechanism of brain ageing that depends on Hcy concentration and expression of MARS enzyme. Its irreversibility and cumulative occurrence throughout life may explain why B12 and folate supplementation of the elderly has limited effects, if any, to prevent pathological brain ageing and cognitive decline. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2018

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