36 results on '"Genthon, R."'
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2. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD
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Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Cavedo, E., Chiesa, P., Colliot, O., Dubois, B., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M.O., Hampel, H., Houot, M., Kas, A., Lamari, F., Levy, M., Lista, S., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M.C., Revillon, M., Santos, A., Andrade, K.S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Vergallo, A., Younsi, N., Afshar, Mohammad, Flores Aguilar, Lisi, Akman-Anderson, Leyla, Arenas, Joaquín, Avila, Jesus, Babiloni, Claudio, Baldacci, Filippo, Batrla, Richard, Benda, Norbert, Black, Keith L., Bokde, Arun L.W., Bonuccelli, Ubaldo, Broich, Karl, Cacciola, Francesco, Caraci, Filippo, Castrillo, Juan, Cavedo, Enrica, Ceravolo, Roberto, Chiesa, Patrizia A., Corvol, Jean-Christophe, Claudio Cuello, Augusto, Cummings, Jeffrey L., Depypere, Herman, Dubois, Bruno, Duggento, Andrea, Emanuele, Enzo, Escott-Price, Valentina, Federoff, Howard, Teresa Ferretti, Maria, Fiandaca, Massimo, Frank, Richard A., Garaci, Francesco, Geerts, Hugo, Giorgi, Filippo S., Goetzl, Edward J., Graziani, Manuela, Haberkamp, Marion, Marie-Odile, Habert, Hampel, Harald, Herholz, Karl, Hernandez, Felix, Kapogiannis, Dimitrios, Karran, Eric, Kiddle, Steven J., Kim, Seung H., Koronyo, Yosef, Koronyo-Hamaoui, Maya, Langevin, Todd, Lehéricy, Stéphane, Lucía, Alejandro, Lista, Simone, Lorenceau, Jean, Mango, Dalila, Mapstone, Mark, Neri, Christian, Nisticò, Robert, O'Bryant, Sid E., Palermo, Giovanni, Perry, George, Ritchie, Craig, Rossi, Simone, Saidi, Amira, Santarnecchi, Emiliano, Schneider, Lon S., Sporns, Olaf, Toschi, Nicola, Verdooner, Steven R., Vergallo, Andrea, Villain, Nicolas, Welikovitch, Lindsay A., Woodcock, Janet, Younesi, Erfan, Houot, Marion, Lemercier, Pablo, Vanmechelen, Eugeen, De Vos, Ann, Habert, Marie-Odile, and Potier, Marie-Claude
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- 2019
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3. Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
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Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Cavedo, E., Chiesa, P., Colliot, O., Dubois, B., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M.O., Hampel, H., Houot, M., Kas, A., Lamari, F., Levy, M., Lista, S., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M.C., Revillon, M., Santos, A., Andrade, K.S., Sole, M., Surtee, M., de Schotten M, Thiebaud, Vergallo, A., Younsi, N., Aguilar, Lisi Flores, Babiloni, Claudio, Baldacci, Filippo, Benda, Norbert, Black, Keith L., Bokde, Arun L.W., Bonuccelli, Ubaldo, Broich, Karl, Cacciola, Francesco, Castrillo, Juan, Cavedo, Enrica, Ceravolo, Roberto, Chiesa, Patrizia A., Corvol, Jean-Christophe, Cuello, Augusto Claudio, Cummings, Jeffrey L., Depypere, Herman, Dubois, Bruno, Duggento, Andrea, Escott-Price, Valentina, Federoff, Howard, Ferretti, Maria Teresa, Fiandaca, Massimo, Frank, Richard A., Garaci, Francesco, Geerts, Hugo, Giorgi, Filippo S., Graziani, Manuela, Haberkamp, Marion, Habert, Marie-Odile, Hampel, Harald, Herholz, Karl, Karran, Eric, Kim, Seung H., Koronyo, Yosef, Koronyo-Hamaoui, Maya, Lamari, Foudil, Langevin, Todd, Lehéricy, Stéphane, Lista, Simone, Lorenceau, Jean, Mango, Dalila, Mapstone, Mark, Neri, Christian, Nisticò, Robert, O'Bryant, Sid E., Perry, George, Ritchie, Craig, Rossi, Simone, Saidi, Amira, Santarnecchi, Emiliano, Schneider, Lon S., Sporns, Olaf, Toschi, Nicola, Verdooner, Steven R., Vergallo, Andrea, Villain, Nicolas, Welikovitch, Lindsay A., Woodcock, Janet, Younesi, Erfan, Mégret, Lucile, Zetterberg, Henrik, Blennow, Kaj, Vanmechelen, Eugeen, De Vos, Ann, and Potier, Marie-Claude
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- 2019
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4. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
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Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P.A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, B., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M.O., Hampel, H., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M.C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M.C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L.F., Babiloni, C., Benda, N., Black, K.L., Bokde, A.L.W., Bonuccelli, U., Broich, K., Bun, R.S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C.M., Corvol, J.C., Cuello, A.C., Cummings, J.L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M.T., Fiandaca, M., Frank, R.A., Garaci, F., George, N., Giorgi, F.S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S.H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lehéricy, S., Lorenceau, J., Mapstone, M., Neri, C., Nisticò, R., Nyasse-Messene, F., O'Bryant, S.E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L.S., Sporns, O., Toschi, N., Verdooner, S.R., Vergallo, A., Villain, N., Welikovitch, L., Woodcock, J., Younesi, E., Vergallo, Andrea, Bun, René-Sosata, Toschi, Nicola, Baldacci, Filippo, Zetterberg, Henrik, Blennow, Kaj, Cavedo, Enrica, Lamari, Foudil, Habert, Marie-Odile, Dubois, Bruno, Floris, Roberto, Garaci, Francesco, Lista, Simone, and Hampel, Harald
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- 2018
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5. Effect of Alzheimer's disease risk and protective factors on cognitive trajectories in subjective memory complainers: An INSIGHT-preAD study
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Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P.A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, B., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M.O., Hampel, H., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M.C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M.C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Teipel, Stefan J., Cavedo, Enrica, Lista, Simone, Habert, Marie-Odile, Potier, Marie-Claude, Grothe, Michel J., Epelbaum, Stephane, Sambati, Luisa, Gagliardi, Geoffroy, Toschi, Nicola, Greicius, Michael D., Dubois, Bruno, and Hampel, Harald
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- 2018
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6. Evaluation of amyloid status in a cohort of elderly individuals with memory complaints: validation of the method of quantification and determination of positivity thresholds
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Habert, Marie-Odile, Bertin, Hugo, Labit, Mickael, Diallo, Mamadou, Marie, Sullivan, Martineau, Kelly, Kas, Aurélie, Causse-Lemercier, Valérie, Bakardjian, Hovagim, Epelbaum, Stéphane, Chételat, Gael, Houot, Marion, Hampel, Harald, Dubois, Bruno, Mangin, Jean-François, Audrain, C., Bakardjian, H., Benali, H., Bertin, H., Boukadida, L., Cacciamani, F., Causse-Lemercier, V., Cavedo, E., Chiesa, P., Colliot, O., Dos Santos, A., Dubois, B., Durrleman, S., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M.-O., Hampel, H., Jungalee, N., Kas, A., Lehericy, S., Lamari, F., Letondor, C., Levy, M., Lista, S., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Rojkova, K., Roy, P., Santos-Andrade, K., Santos, A., Simon, V., Sole, M., Tandetnik, C., Thiebaud De Schotten, M., and INSIGHT-AD study group
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- 2017
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7. Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease
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Penner, G, Lecocq, S, Chopin, A, Vedoya, X, Lista, S, Vergallo, A, Cavedo, E, Lejeune, F, Dubois, B, Hampel, H, Bakardjian, H, Benali, H, Bertin, H, Bonheur, J, Boukadida, L, Boukerrou, N, Chiesa, Pa, Colliot, O, Dubois, M, Epelbaum, S, Gagliardi, G, Genthon, R, Habert, M, Houot, M, Kas, A, Lamari, F, Levy, M, Metzinger, C, Mochel, F, Nyasse, F, Poisson, C, Potier, M, Revillon, M, Santos, A, Andrade, Ks, Sole, M, Surtee, M, de Schotten, Mt, Younsi, N, Afshar, M, Aguilar, Lf, Akman-Anderson, L, Aremas, J, Avila, J, Babiloni, C, Baldacci, F, Batrla, R, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Cacciola, F, Caraci, F, Caruso, G, Castrillo, J, Ceravolo, R, Corbo, M, Corvol, J, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Emanuele, E, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Geerts, H, Giacobini, E, Giorgi, Fs, Goetzl, Ej, Graziani, M, Haberkamp, M, Hanisch, B, Herholz, K, Hernandez, F, Imbimbo, Bp, Kapogiannis, D, Karran, E, Kiddle, Sj, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehericy, S, Lemercier, P, Llavero, F, Lorenceau, J, Lucia, A, Mango, D, Mapstone, M, Neri, C, Nistico, R, O'Bryant, Se, Palermo, G, Perry, G, Ritchie, C, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Valenzuela, Pl, Vellas, B, Verdooner, Sr, Villain, N, Giudici, Kv, Watling, M, Welikovitch, La, Woodcock, J, Younesi, E, Zugaza, Jl, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), 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), 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), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), 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), and Gasset, Maria
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Male ,Aging ,Amyloid β ,MESH: SELEX Aptamer Technique ,[SDV]Life Sciences [q-bio] ,Oligonucleotides ,Artificial Gene Amplification and Extension ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Pathology and Laboratory Medicine ,Biochemistry ,Polymerase Chain Reaction ,Diagnostic Radiology ,Negative selection ,Medical Conditions ,Mathematical and Statistical Techniques ,0302 clinical medicine ,MESH: Aged, 80 and over ,MESH: Early Diagnosis ,80 and over ,Medicine and Health Sciences ,Biomarker discovery ,Tomography ,Aged, 80 and over ,MESH: Aged ,screening and diagnosis ,0303 health sciences ,Multidisciplinary ,Nucleotides ,Mathematical Models ,Radiology and Imaging ,SELEX Aptamer Technique ,Settore MED/37 - Neuroradiologia ,Neurodegenerative Diseases ,MESH: Case-Control Studies ,MESH: Amyloid beta-Peptides ,Detection ,Neurology ,Neurological ,Medicine ,Biomedical Imaging ,Female ,Biotechnology ,4.2 Evaluation of markers and technologies ,Research Article ,Amyloid ,General Science & Technology ,Imaging Techniques ,Science ,Aptamer ,Neuroimaging ,and over ,Computational biology ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Clinical Research ,Diagnostic Medicine ,Alzheimer Disease ,Mental Health and Psychiatry ,Acquired Cognitive Impairment ,Humans ,Risk factor ,Molecular Biology Techniques ,Molecular Biology ,Aged ,030304 developmental biology ,Amyloid beta-Peptides ,MESH: Humans ,Prevention ,Neurosciences ,Alzheimer Precision Medicine Initiative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Biology and Life Sciences ,Omics ,MESH: Male ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Early Diagnosis ,Case-Control Studies ,MESH: Biomarkers ,Dementia ,INSIGHT-preAD study group ,MESH: Female ,Biomarkers ,Positron Emission Tomography ,030217 neurology & neurosurgery ,MESH: Alzheimer Disease ,Neuroscience - Abstract
International audience; The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer's disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
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- 2021
8. Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease
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Chiesa P. A., Cavedo E., Vergallo A., Lista S., Potier M. -C., Habert M. -O., Dubois B., Thiebaut de Schotten M., Hampel H., Audrain C., Auffret A., Bakardjian H., Baldacci F., Batrancourt B., Benakki I., Benali H., Bertin H., Bertrand A., Boukadida L., Cacciamani F., Causse V., Cherif Touil S., Colliot O., Dalla Barba G., Depaulis M., Dos Santos A., Dubois M., Epelbaum S., Fontaine B., Francisque H., Gagliardi G., Genin A., Genthon R., Glasman P., Gombert F., Habert M. O., Hewa H., Houot M., Jungalee N., Kas A., Kilani M., La Corte V., Le Roy F., Lehericy S., Letondor C., Levy M., Lowrey M., Ly J., Makiese O., Masetti I., Mendes A., Metzinger C., Michon A., Mochel F., Nait Arab R., Nyasse F., Perrin C., Poirier F., Poisson C., Potier M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Uspenskaya O., Vlaincu M., Aguilar L. F., Babiloni C., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Corvol J. -C., Claudio Cuello A., Cummings J. L., Depypere H., Duggento A., Durrleman S., Escott-Price V., Federoff H., Teresa Ferretti M., Fiandaca M., Frank R. A., Garaci F., Geerts H., George N., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lorenceau J., Mango D., Mapstone M., Neri C., Nistico R., O'Bryant S. E., Palermo G., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E., 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), Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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), Treat SVD, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), Université de Bordeaux (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Maladies Cognitives et Comportementales [Paris], Fraunhofer Center for Assistive Information and Communication Solutions [Porto] (Fraunhofer AICOS), Fraunhofer (Fraunhofer-Gesellschaft), Ariana Pharmaceuticals, McGill University = Université McGill [Montréal, Canada], Universidad Autonoma de Madrid (UAM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Pisa - Università di Pisa, Federal Institute of Drugs and Medical Devices [Bonn], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universita degli Studi di Messina, University of Catania [Italy], University of Cambridge [UK] (CAM), Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Università degli Studi di Roma Tor Vergata [Roma], University of Pavia, Cardiff University, Universität Zürich [Zürich] = University of Zurich (UZH), University of California [Irvine] (UCI), University of California, Siemens Healthineers, Digital Services, Digital Technology and Innovation, In Silico Biosciences (ISB), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of California [San Francisco] (UCSF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Manchester [Manchester], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Abbvie Inc. [North Chicago], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Britsh Columbia [Vancouver], Cedars-Sinai Medical Center, Functional Neuromodulation, CIBER de Enfermedades Raras (CIBERER), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute [Rome, Italy] (EBRI), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), University of North Texas Health Science Center [Fort Worth], University of Auckland [Auckland], University of Edinburgh, Università degli Studi di Siena = University of Siena (UNISI), Harvard Medical School [Boston] (HMS), Keck School of Medicine [Los Angeles], University of Southern California (USC), Indiana State University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), NeuroVision Imaging, Fondation pour la Recherche sur Alzheimer, Center for Drug Evaluation and Research (CDER), European Society for Translational Medicine (EUSTM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fraunhofer AICOS [Porto], McGill University, Sapienza University [Rome], University of Zürich [Zürich] (UZH), Università degli Studi di Roma 'La Sapienza' [Rome], CHU Pitié-Salpêtrière [APHP], Service de neuro-radiologie [CHU Pitié-Salpêtrière], Università degli Studi di Siena (UNISI), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), 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], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Universidad Autónoma de Madrid (UAM), 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), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Sans affiliation, 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), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Pavia = University of Pavia (UNIPV), University of California [Irvine] (UC Irvine), University of California (UC), University of California [San Francisco] (UC San Francisco), University of British Columbia [Vancouver], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M. -C., Habert, M. -O., Dubois, B., Thiebaut de Schotten, M., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Castrillo, J., Ceravolo, R., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Apolipoprotein E ,Epidemiology ,Brain activity and meditation ,Precuneus ,Disease ,Neuropsychological Tests ,Hippocampus ,Cohort Studies ,[SCCO]Cognitive science ,0302 clinical medicine ,Medicine ,Longitudinal Studies ,Default mode network ,ComputingMilieux_MISCELLANEOUS ,Brain Mapping ,Subjective memory complaints ,Brain functional dynamic ,Health Policy ,Precision medicine ,fMRI ,Settore BIO/14 ,Brain ,Brain functional dynamics ,Alzheimer's disease ,Magnetic Resonance Imaging ,Temporal Lobe ,Frontal Lobe ,Psychiatry and Mental health ,medicine.anatomical_structure ,Cohort ,Biomarker (medicine) ,Female ,Amyloid ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Apolipoproteins E ,Developmental Neuroscience ,Alzheimer Disease ,Humans ,Aged ,Resting state fMRI ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,030104 developmental biology ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
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- 2019
9. Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study
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Baldacci, F., Lista, S., Manca, M. L., Chiesa, P. A., Cavedo, E., Lemercier, P., Zetterberg, H., Blennow, K., Habert, M. -O., Potier, M. C., Dubois, B., Vergallo, A., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Houot, M., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. -C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., de Schotten, M. T., Younsi, N., Afshar, M., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Caruso, G., Castrillo, J., Ceravolo, R., Corbo, M., Corvol, J. -C., Claudio, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., Zugaza, J. L., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), 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), University of Pisa - Università di Pisa, 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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Sahlgrenska Academy at University of Gothenburg [Göteborg], University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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Male ,BIOMARKER ,0301 basic medicine ,Oncology ,Aging ,Neurology ,[SDV]Life Sciences [q-bio] ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Medical and Health Sciences ,lcsh:RC346-429 ,MESH: Cognitive Dysfunction ,Alzheimer’s disease ,Biomarkers ,Mild cognitive impairment ,Neurofilament light chain ,Subjective memory complainers ,Tau ,0302 clinical medicine ,Neurofilament Proteins ,Medicine and Health Sciences ,BRAIN ,MESH: Neurofilament Proteins ,RISK ,Settore FIS/07 ,NEURODEGENERATION ,Cognition ,ASSOCIATION ,MESH: Follow-Up Studies ,Alzheimer's disease ,MESH: Amyloid beta-Peptides ,MESH: tau Proteins ,ALZHEIMERS-DISEASE ,POSITIVITY ,Neurological ,Cohort ,Biomarker (medicine) ,Female ,medicine.medical_specialty ,Cognitive Neuroscience ,tau Proteins ,Subjective ,Affect (psychology) ,VALIDATION ,lcsh:RC321-571 ,subjective memory complainers ,mild cognitive impairment ,biomarkers ,s disease ,03 medical and health sciences ,memory complainers ,Clinical Research ,Alzheimer Disease ,Internal medicine ,NEUROFILAMENT LIGHT-CHAIN ,Acquired Cognitive Impairment ,medicine ,Humans ,Cognitive Dysfunction ,Vitamin B12 ,Allele ,Alzheimer’ ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,lcsh:Neurology. Diseases of the nervous system ,Amyloid beta-Peptides ,MESH: Humans ,business.industry ,Research ,Prevention ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer Precision Medicine Initiative ,COGNITIVE IMPAIRMENT ,MESH: Male ,Brain Disorders ,030104 developmental biology ,MESH: Biomarkers ,Dementia ,Neurology (clinical) ,business ,INSIGHT-preAD study group ,MESH: Female ,MESH: Alzheimer Disease ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
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- 2020
10. Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD
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Cacciamani, F., Sambati, L., Houot, M., Habert, M. -O., Dubois, B., Epelbaum, S., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hampel, H., Hewa, H., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-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], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], CATI Multicenter Neuroimaging Platform (CATI), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Supported by NIH (OR 76675882).The study was promoted by INSERM in collaboration with ICM, and Pfizerand has received support within the'Investissement d’Avenir'(ANR-10-AIHU-06) program. The study was promoted in collaboration with the'CHU deBordeaux'(coordination CIC EC7), the promoter of Memento cohort, fundedby the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. This project/research has received funding from the European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2).The funding sources had no role in the study design, data collection, data analysis, or data interpretation., 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), 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), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), 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), Service de médecine nucléaire [CHU Pitié-Salpétrière], Centre de Recherche en Myologie, 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)-Sorbonne Université (SU), 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], 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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Male ,Amyloid ,medicine.medical_specialty ,Neurology ,genetic structures ,Awareness ,Brain ,Cognitive decline ,Preclinical Alzheimer’s disease ,[SDV]Life Sciences [q-bio] ,Cognitive Neuroscience ,Disease ,Asymptomatic ,lcsh:RC346-429 ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Memory ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Amyloid burden ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,lcsh:Neurology. Diseases of the nervous system ,Amyloid beta-Peptides ,030214 geriatrics ,business.industry ,Research ,Cognition ,Cohort ,Disease Progression ,Neurology (clinical) ,medicine.symptom ,business ,Biomarkers ,030217 neurology & neurosurgery ,Geriatric psychiatry - Abstract
Background Lack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer’s disease (AD). Recent studies showed that ACD can also be reduced in the early stages. Methods We described different trends of evolution of ACD over 3 years in a cohort of memory-complainers and their association to amyloid burden and brain metabolism. We studied the impact of ACD at baseline on cognitive scores’ evolution and the association between longitudinal changes in ACD and in cognitive score. Results 76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a steadily heightened ACD and were comparable to those with accurate ACD in terms of demographic characteristics and AD biomarkers. 4.25% constantly showed low ACD, had significantly higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution and no association between longitudinal changes in ACD and in cognitive scores. Conclusions ACD begins to decrease during the preclinical phase in a group of individuals, who are of great interest and need to be further characterized. Trial registration The present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42.
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- 2020
11. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
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Vergallo, A, Bun, R, Toschi, N, Baldacci, F, Zetterberg, H, Blennow, K, Cavedo, E, Lamari, F, Habert, M, Dubois, B, Floris, R, Garaci, F, Lista, S, Hampel, H, Audrain, C, Auffret, A, Bakardjian, H, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cherif Touil, S, Chiesa, Pa, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, Mo, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, Mc, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, Mc, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Aguilar, Lf, Babiloni, C, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Coman, Cm, Corvol, Jc, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehéricy, S, Lorenceau, J, Mapstone, M, Neri, C, Nisticò, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rossi, S, Santarnecchi, E, Schneider, Ls, Sporns, O, Verdooner, Sr, Villain, N, Welikovitch, L, Woodcock, J, Younesi, E, Vergallo, A., Bun, R. -S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M. -O., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Bun, R. S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C. M., Corvol, J. C., Cuello, A. C., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lorenceau, J., Mapstone, M., Neri, C., Nistico, R., Nyasse-Messene, F., O'Bryant, S. E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L. S., Sporns, O., Verdooner, S. R., Villain, N., Welikovitch, L., Woodcock, J., and Younesi, E.
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0301 basic medicine ,Epidemiology ,Alzheimer's disease ,Amyloid PET ,Cerebrospinal fluid ,Monocentric ,Preclinical ,Subjective memory complainers ,SUVR ,Synergistic ,Tau protein ,α-Synuclein ,chemistry.chemical_compound ,0302 clinical medicine ,biology ,Health Policy ,Settore FIS/07 ,Settore BIO/14 ,Pathophysiology ,Psychiatry and Mental health ,medicine.symptom ,medicine.medical_specialty ,Amyloid ,Asymptomatic ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychiatry and Mental Health ,Internal medicine ,mental disorders ,medicine ,Dementia ,Alpha-synuclein ,business.industry ,Alzheimer's disease biomarkers ,medicine.disease ,030104 developmental biology ,Endocrinology ,nervous system ,chemistry ,Subjective memory complainer ,biology.protein ,business ,030217 neurology & neurosurgery - Abstract
Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
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- 2018
12. Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia
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Slot, R.E.R. Sikkes, S.A.M. Berkhof, J. Brodaty, H. Buckley, R. Cavedo, E. Dardiotis, E. Guillo-Benarous, F. Hampel, H. Kochan, N.A. Lista, S. Luck, T. Maruff, P. Molinuevo, J.L. Kornhuber, J. Reisberg, B. Riedel-Heller, S.G. Risacher, S.L. Roehr, S. Sachdev, P.S. Scarmeas, N. Scheltens, P. Shulman, M.B. Saykin, A.J. Verfaillie, S.C.J. Visser, P.J. Vos, S.J.B. Wagner, M. Wolfsgruber, S. Jessen, F. Boada, M. de Deyn, P.P. Jones, R. Frisoni, G. Spiru, L. Nobili, F. Freund-Levi, Y. Soininen, H. Verhey, F. Wallin, Å.K. Touchon, J. Rikkert, M.O. Rigaud, A.-S. Bullock, R. Tsolaki, M. Vellas, B. Wilcock, G. Froelich, L. Bakardjian, H. Benali, H. Bertin, H. Bonheur, J. Boukadida, L. Boukerrou, N. Chiesa, P. Colliot, O. Dubois, B. Dubois, M. Epelbaum, S. Gagliardi, G. Genthon, R. Habert, M.-O. Houot, M. Kas, A. Lamari, F. Levy, M. Metzinger, C. Mochel, F. Nyasse, F. Poisson, C. Potier, M.-C. Revillon, M. Santos, A. Andrade, K.S. Sole, M. Surtee, M. Thiebaud de Schotten, M. Vergallo, A. Younsi, N. van der Flier, W.M. Alzheimer's Disease Neuroimaging Initiative DESCRIPA working group INSIGHT-preAD study group SCD-I working group
- Abstract
Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini–Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts. © 2018 The Authors
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- 2019
13. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD
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Vergallo, A., Houot, M., Cavedo, E., Lemercier, P., Vanmechelen, E., De Vos, A., Habert, M. -O., Potier, M. -C., Dubois, B., Lista, S., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M. O., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Younsi, N., Afshar, M., Flores Aguilar, L., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Castrillo, J., Ceravolo, R., Chiesa, P. A., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Marie-Odile, H., Herholz, K., Hernandez, F., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lucia, A., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), 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), 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), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de médecine nucléaire [CHU Pitié-Salpétrière]
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Male ,0301 basic medicine ,Apolipoprotein E ,Epidemiology ,[SDV]Life Sciences [q-bio] ,PROGRESSION ,Disease ,Cognition ,0302 clinical medicine ,Amyloid precursor protein ,Medicine and Health Sciences ,Aspartic Acid Endopeptidases ,medicine.diagnostic_test ,biology ,Health Policy ,Settore BIO/14 ,Brain ,Alzheimer's disease ,Healthy Volunteers ,3. Good health ,GENOTYPE ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,Positron emission tomography ,Cohort ,Biomarker (medicine) ,Female ,EXPRESSION ,medicine.medical_specialty ,BIOMARKERS ,Standardized uptake value ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Sexual dimorphism ,Apolipoproteins E ,Sex Factors ,Developmental Neuroscience ,Alzheimer Disease ,Internal medicine ,mental disorders ,medicine ,Humans ,BACE1 biomarkers ,Aged ,Plasma BACE1 ,DECLINE ,Amyloid beta-Peptides ,business.industry ,030104 developmental biology ,Endocrinology ,Positron-Emission Tomography ,Disease modifying ,biology.protein ,Neurology (clinical) ,Amyloid Precursor Protein Secretases ,Geriatrics and Gerontology ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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- 2019
14. Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease
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Cacciamani, Federica, Tandetnik, Caroline, Gagliardi, Geoffroy, Bertin, Hugo, Habert, Marie-Odile, Hampel, Harald, Boukadida, Laurie, Révillon, Marie, Epelbaum, Stéphane, Dubois, Bruno, Audrain, C, Auffret, A, Bakardjian, H, Baldacci, F, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cavedo, E, Cherif Touil, S, Chiesa, P A, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, B, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, M O, Hampel, H, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lista, S, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, M C, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, M C, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique et d'Ingénierie de Bordeaux (I2M), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuroradiologie [CHU Pitié-Salpêtrière], École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-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)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP]-Inria de Paris, Cacciamani, Federica, Tandetnik, Caroline, Gagliardi, Geoffroy, Bertin, Hugo, Habert, Marie-Odile, Hampel, Harald, Boukadida, Laurie, Révillon, Marie, Epelbaum, Stéphane, Dubois, Bruno, Audrain, C, Auffret, A, Bakardjian, H, Baldacci, F, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cavedo, E, Cherif Touil, S, Chiesa, P A, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, B, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, M O, Hampel, H, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lista, S, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, M C, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, M C, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris
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Male ,Ethylene Glycol ,[SDV]Life Sciences [q-bio] ,awarene ,Neuropsychological Tests ,Alzheimer’s disease ,awareness ,biomarkers ,cognitive complaints ,subjective cognitive decline ,Aged ,Aged, 80 and over ,Alzheimer Disease ,Analysis of Variance ,Aniline Compounds ,Brain ,Brain Mapping ,Cognitive Dysfunction ,Ethylene Glycols ,Female ,Functional Laterality ,Humans ,Positron-Emission Tomography ,Psychiatric Status Rating Scales ,Surveys and Questionnaires ,Awareness ,cognitive complaint ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,80 and over ,Surveys and Questionnaire ,Aniline Compound ,Psychiatric Status Rating Scale ,Alzheimer's disease ,Clinical Psychology ,Psychiatry and Mental Health ,biomarker ,Neuropsychological Test ,Geriatrics and Gerontology ,Human - Abstract
International audience; Background:Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer’s disease (AD). Objective:In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Methods:Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Results:Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the “low awareness” group showed greater amyloid burden and lower cortical metabolism, compared to the “high awareness” group. Conclusion:This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.
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- 2017
15. Basal Forebrain Volume, but Not Hippocampal Volume, Is a Predictor of Global Cognitive Decline in Patients With Alzheimer's Disease Treated With Cholinesterase Inhibitors
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Teipel, Sj, Cavedo, E, Hampel, H, Grothe, Mj, Aguilar, Lf, Babiloni, C, Baldacci, F, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Chiesa, Pa, Colliot, O, Coman, C, Corvol, J, Cuello, Ac, Depypere, H, Dubois, B, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Genthon, R, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Habert, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Lamari, F, Langevin, T, Lehericy, S, Lista, S, Lorenceau, J, Mapstone, M, Neri, C, Nistico, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rojkova, K, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Verdooner, Sr, Vergallo, A, Villain, N, Welikovitch, La, Woodcock, J, Younesi, E, and Cummings, Jl
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Aging ,hippocampus ,Hippocampus ,Neurodegenerative ,Alzheimer's Disease ,lcsh:RC346-429 ,cholinergic treatment ,memory ,0302 clinical medicine ,Medicine and Health Sciences ,Psychology ,Medicine ,Cognitive decline ,Episodic memory ,basal forebrain ,Original Research ,Basal forebrain ,Settore FIS/07 ,05 social sciences ,Cognition ,IMPAIRMENT ,Manchester Institute for Collaborative Research on Ageing ,Neurology ,Neurological ,Cohort ,DONEPEZIL ,Cardiology ,NUCLEUS BASALIS ,ADAS-COG ,MRI ,CHOLINERGIC SYSTEM ,medicine.medical_specialty ,ResearchInstitutes_Networks_Beacons/MICRA ,Clinical Sciences ,COMPOSITE SCORE ,ATROPHY ,050105 experimental psychology ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Behavioral and Social Science ,Acquired Cognitive Impairment ,Dementia ,0501 psychology and cognitive sciences ,ddc:610 ,lcsh:Neurology. Diseases of the nervous system ,business.industry ,Alzheimer's Disease Neuroimaging Initiative ,Neurosciences ,Alzheimer Precision Medicine Initiative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,prediction ,medicine.disease ,NEUROIMAGING INITIATIVE ADNI ,Brain Disorders ,SUBSTANTIA INNOMINATA ,executive function ,Cholinergic treatment ,Executive function ,Memory ,Prediction ,Cholinergic ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background: Predicting the progression of cognitive decline in Alzheimer's disease (AD) is important for treatment selection and patient counseling. Structural MRI markers such as hippocampus or basal forebrain volumes might represent useful instruments for the prediction of cognitive decline. The primary objective was to determine the predictive value of hippocampus and basal forebrain volumes for global and domain specific cognitive decline in AD dementia during cholinergic treatment.Methods: We used MRI and cognitive data from 124 patients with the clinical diagnosis of AD dementia, derived from the ADNI-1 cohort, who were on standard of care cholinesterase inhibitor treatment during a follow-up period between 0.4 and 3.1 years. We used linear mixed effects models with cognitive function as outcome to assess the main effects as well as two-way interactions between baseline volumes and time controlling for age, sex, and total intracranial volume. This model accounts for individual variation in follow-up times.Results: Basal forebrain volume, but not hippocampus volume, was a significant predictor of rates of global cognitive decline. Larger volumes were associated with smaller rates of cognitive decline. Left hippocampus volume had a modest association with rates of episodic memory decline. Baseline performance in global cognition and memory was significantly associated with hippocampus and basal forebrain volumes; in addition, basal forebrain volume was associated with baseline performance in executive function.Conclusions: Our findings indicate that in AD dementia patients, basal forebrain volume may be a useful marker to predict subsequent cognitive decline during cholinergic treatment.
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- 2018
16. Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults
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ten Kate, Mara, Visser, Pieter Jelle, Bakardjian, Hovagim, Barkhof, Frederik, Sikkes, Sietske A. M., van der Flier, Wiesje M., Scheltens, Philip, Hampel, Harald, Habert, Marie-Odile, Dubois, Bruno, Tijms, Betty M., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, B., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hampel, H., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AXA Research Fund, Sorbonne Université (SU), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Neurology, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
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0301 basic medicine ,PRECLINICAL ALZHEIMERS-DISEASE ,Aging ,0302 clinical medicine ,Original Research ,biology ,medicine.diagnostic_test ,subjective memory complaints ,APOE GENOTYPE ,Alzheimer's disease ,medicine.anatomical_structure ,Cerebral cortex ,Positron emission tomography ,Cardiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,STRUCTURAL COVARIANCE ,Alzheimer’s disease ,MRI ,medicine.medical_specialty ,Amyloid ,Amyloid beta ,Cognitive Neuroscience ,graph theory ,PLAQUE BURDEN ,Standardized uptake value ,Cognitive neuroscience ,SPATIAL-PATTERNS ,gray matter network ,lcsh:RC321-571 ,Graph theory ,Gray matter network ,PET ,Subjective memory complaints ,03 medical and health sciences ,POSITRON-EMISSION-TOMOGRAPHY ,Internal medicine ,CEREBRAL-CORTEX ,medicine ,Dementia ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Pathological ,business.industry ,HUMAN CORTICAL NETWORKS ,medicine.disease ,amyloid beta ,BRAIN NETWORKS ,030104 developmental biology ,PROSPECTIVE COHORT ,biology.protein ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
for the INSIGHT-preAD study group; International audience; The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [ 18 F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (β = −0.12, p < 0.05), and small world values (β = −0.16, p < 0.01). Associations were most prominent in orbito-and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.
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- 2018
17. Kinetics, Safety, and Efficacy of Ramipril After Long-Term Administration in Hemodialyzed Patients
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Fillastre, J. P., primary, Baguet, J. C., additional, Dubois, D., additional, Vauquier, J., additional, Godin, M., additional, Legallicier, B., additional, Luus, H. G., additional, de la Rey, N., additional, Carcone, N., additional, and Genthon, R., additional
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- 1996
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18. Validity and reliability of the German language SF-36 health survey in patients with amyotrophic lateral sclerosis | Validität und Reliabilität der Deutschen fassung des SF-36 bei patienten mit amyotropher lateralsklerose
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Pongratz, D., Zierz, S., Fischer, W., Jenkinson, C., Fitzpatrick, R., Peto, V., Swash, M., Aarli, J. A., Burgunder, J. -M, Evangelista, T., Genthon, R., Hardiman, O., Illa, I., Leigh, P. N., Ludin, H. -P, Mazzini, L., Meininger, V., Mora, J. S., Ortega, M., Papapetropoulos, T., Pouget, J., Robberecht, W., Ronnevi, L. -O, Sales-Luis, M., Vincenzo Silani, Wokke, J. H. J., and Werdelin, L.
19. Validity and reliability of the German language SF-36 health survey in patients with amyotrophic lateral sclerosis,Validität und Reliabilität der Deutschen fassung des SF-36 bei patienten mit amyotropher lateralsklerose
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Pongratz, D., Zierz, S., Fischer, W., Jenkinson, C., Fitzpatrick, R., Peto, V., Michael Swash, Aarli, J. A., Burgunder, J. -M, Evangelista, T., Genthon, R., Hardiman, O., Illa, I., Leigh, P. N., Ludin, H. -P, Mazzini, L., Meininger, V., Mora, J. S., Ortega, M., Papapetropoulos, T., Pouget, J., Robberecht, W., Ronnevi, L. -O, Sales-Luis, M., Silani, V., Wokke, J. H. J., and Werdelin, L.
20. How to treat hypertensive uraemic patients with ramirril. Results of a pharmacodynamic and pharmacokinetic study in hemodialysis patients
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Fillastre, J.P., Baguet, J.C., Dubois, D., and Genthon, R.
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- 1995
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21. Letters.
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Martin, Deac, Smith, Dede, Dailey, Barbara J., Pellegrini, Vittorio, Wolfe, Richard F., Lyons, Frances, Gibson, Michael F., Munoz, Socorro, Fisher, Louis, Whitman, C. N., Johnson, G. E., Genthon, R. M., Firley, Anthony A., and Payne, Carroll
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LETTERS to the editor , *FICTION - Abstract
Presents letters to the editor referencing articles and topics discussed in previous issues. "To Get Rave Reviews, Write An Anti-U.S. Novel!," which focused on the book "The Quiet American," by Graham Greene; "Mightiest Menu in Manhattan," which discussed the New York City; "Hollywood's Melancholy Blonde," by Dean Jennings, which focused on Kim Novak.
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- 1956
22. Validation study of "Santé-Cerveau", a digital tool for early cognitive changes identification.
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Lesoil C, Bombois S, Guinebretiere O, Houot M, Bahrami M, Levy M, Genthon R, Bozon F, Jean-Marie H, Epelbaum S, Foulon P, Villain N, and Dubois B
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- Humans, Aged, Adult, Middle Aged, Neuropsychological Tests, Cognition, COVID-19 complications, Cognition Disorders diagnosis, Cognitive Dysfunction psychology, Alzheimer Disease diagnosis
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Background: There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability., Methods: Three groups were constituted including 65 elderly Controls, 64 patients with neurodegenerative diseases (NDG): 50 AD and 14 non-AD, and 20 post-COVID-19 patients. The minimum MMSE score for inclusion was 20. Association between computerized SCD-T cognitive tests and their standard equivalent was assessed using Pearson's correlation coefficients. Two algorithms (a simple clinician-guided algorithm involving the 5-WT and the NCT; and a machine learning classifier based on 8 scores from the SCD-T tests extracted from a multiple logistic regression model, and data from the SCD-T questionnaires) were evaluated. The acceptability of SCD-T was investigated through a questionnaire and scale., Results: AD and non-AD participants were older (mean ± standard deviation (SD): 72.61 ± 6.79 vs 69.91 ± 4.86 years old, p = 0.011) and had a lower MMSE score (Mean difference estimate ± standard error: 1.74 ± 0.14, p < 0.001) than Controls; post-COVID-19 patients were younger than Controls (mean ± SD: 45.07 ± 11.36 years old, p < 0.001). All the computerized SCD-T cognitive tests were significantly associated with their reference version. In the pooled Controls and NDG group, the correlation coefficient was 0.84 for verbal memory, -0.60 for executive functions, and 0.72 for global intellectual efficiency. The clinician-guided algorithm demonstrated 94.4% ± 3.8% sensitivity and 80.5% ± 8.7% specificity, and the machine learning classifier 96.8% ± 3.9% sensitivity and 90.7% ± 5.8% specificity. The acceptability of SCD-T was good to excellent., Conclusions: We demonstrate the high accuracy of SCD-T in screening cognitive disorders and its good acceptance even in individuals with prodromal and mild dementia stages. SCD-T would be useful in primary care to faster refer subjects with significant cognitive impairment (and limit unnecessary referrals) to specialized consultation, improve the AD care pathway and the pre-screening in clinical trials., (© 2023. The Author(s).)
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- 2023
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23. [Toward a preventive management Alzheimer's disease].
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Dubois B, Bombois S, Villain N, Teichmann M, Epelbaum S, Migliaccio R, Genthon R, Verrat B, Lesoil C, Levy M, Le Ber I, and Levy R
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Dementias, and Alzheimer's disease (AD) in particular, will increasingly become a public health issue. However, three major data may change the severity of these pathologies: in young adults, simple measures of healthy lifestyle (control of vascular risk factors, physical activity and cognitive stimulation), have an impact on a future cognitive decline; the same lifestyle interventions may delay the start of the disease for elderly people potentially at-risk; finally, and for the first time, a monoclonal antibody directed against amyloid lesions has just shown a significant effect on the progression of AD in patients at an early stage of the disease. According to these results, we will have to reconsider the strategy for managing minor or severe cognitive disorders and particularly AD. Nowadays, patients start the care process too late. The solution is to act earlier, even preventively. It is necessary to improve a care offer adapted to this new situation in order to impact on the disease as soon as possible, even before the onset of symptoms, based on: 1) predictive algorithms aimed at establishing whose cognitively unimpaired individuals may further develop the disease; these algorithms will be based on demographic, family, cognitive, genomic and biological data, such as in the "Santé Cerveau" project developed in partnership with the Health Regional Agency (ARS) and the general practitioners; 2)and on some expert centers which must become "dementia prevention clinics" to test prevention measures, initiate and validate multi-domain therapeutic education programs; to disclose about the risk in response to the request of worried patients; and to propose early pharmacological treatments if these individuals are on the way to declare AD in the coming months, taking into account competition between risks. This will allow to prepare to make use of new pharmacological treatments that might be discovered., (© 2020 Published by Elsevier Masson SAS on behalf of l'Académie nationale de médecine.)
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- 2020
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24. Biomarker-guided clustering of Alzheimer's disease clinical syndromes.
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Toschi N, Lista S, Baldacci F, Cavedo E, Zetterberg H, Blennow K, Kilimann I, Teipel SJ, Melo Dos Santos A, Epelbaum S, Lamari F, Genthon R, Habert MO, Dubois B, Floris R, Garaci F, Vergallo A, and Hampel H
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- Aged, Alzheimer Disease diagnosis, Amyloid beta-Peptides cerebrospinal fluid, Cognitive Dysfunction diagnosis, Female, Humans, Male, Middle Aged, Peptide Fragments cerebrospinal fluid, Risk Factors, Alzheimer Disease cerebrospinal fluid, Biomarkers cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, tau Proteins cerebrospinal fluid
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Alzheimer's disease (AD) neuropathology is extremely heterogeneous, and the evolution from preclinical to mild cognitive impairment until dementia is driven by interacting genetic/biological mechanisms not fully captured by current clinical/research criteria. We characterized the heterogeneous "construct" of AD through a cerebrospinal fluid biomarker-guided stratification approach. We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (Aβ
1-42 , t-tau, p-tau181 , NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 ± 10.4, 70.4 ± 7.7, 71.7 ± 8.4, 76.2 ± 3.5 years [mean ± SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters. We found 5 distinct clusters (sizes: N = 38, 16, 24, 14, and 21) whose composition was independent of phenotypical groups. Two clusters showed biomarker profiles linked to neurodegenerative processes not associated with classical AD-related pathophysiology. One cluster was characterized by the neuroinflammation biomarker YKL-40. Combining nonlinear data aggregation with informative biomarkers can generate novel patient strata which are representative of cellular/molecular pathophysiology and may aid in predicting disease evolution and mechanistic drug response., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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25. Precision pharmacology for Alzheimer's disease.
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Hampel H, Vergallo A, Aguilar LF, Benda N, Broich K, Cuello AC, Cummings J, Dubois B, Federoff HJ, Fiandaca M, Genthon R, Haberkamp M, Karran E, Mapstone M, Perry G, Schneider LS, Welikovitch LA, Woodcock J, Baldacci F, and Lista S
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- Alzheimer Disease metabolism, Amyloid beta-Peptides antagonists & inhibitors, Animals, Biomarkers blood, Drug Discovery, Humans, tau Proteins antagonists & inhibitors, Alzheimer Disease drug therapy, Precision Medicine
- Abstract
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses. Consequently, the distinct pattern of AD pathophysiology in space and time must be investigated on the basis of the individual biological makeup. This requires the implementation of systems biology and neurophysiology to facilitate Precision Medicine (PM) and Precision Pharmacology (PP). The regulation of several processes at multiple levels of complexity from gene expression to cellular cycle to tissue repair and system-wide network activation has different time delays (temporal scale) according to the affected systems (spatial scale). The initial failure might originate and occur at every level potentially affecting the whole dynamic interrelated systems within an organism. Unraveling the spatial and temporal dynamics of non-linear pathophysiological mechanisms across the continuum of hierarchical self-organized systems levels and from systems homeostasis to systems failure is key to understand AD. Measuring and, possibly, controlling space- and time-scaled adaptive and compensatory responses occurring during AD will represent a crucial step to achieve the capacity to substantially modify the disease course and progression at the best suitable timepoints, thus counteracting disrupting critical pathophysiological inputs. This approach will provide the conceptual basis for effective disease-modifying pathway-based targeted therapies. PP is based on an exploratory and integrative strategy to complex diseases such as brain proteinopathies including AD, aimed at identifying simultaneous aberrant molecular pathways and predicting their temporal impact on the systems levels. The depiction of pathway-based molecular signatures of complex diseases contributes to the accurate and mechanistic stratification of distinct subcohorts of individuals at the earliest compensatory stage when treatment intervention may reverse, stop, or delay the disease. In addition, individualized drug selection may optimize treatment safety by decreasing risk and amplitude of side effects and adverse reactions. From a methodological point of view, comprehensive "omics"-based biomarkers will guide the exploration of spatio-temporal systems-wide morpho-functional shifts along the continuum of AD pathophysiology, from adaptation to irreversible failure. The Alzheimer Precision Medicine Initiative (APMI) and the APMI cohort program (APMI-CP) have commenced to facilitate a paradigm shift towards effective drug discovery and development in AD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
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26. Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ 1-42 , total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40.
- Author
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Hampel H, Toschi N, Baldacci F, Zetterberg H, Blennow K, Kilimann I, Teipel SJ, Cavedo E, Melo Dos Santos A, Epelbaum S, Lamari F, Genthon R, Dubois B, Floris R, Garaci F, and Lista S
- Subjects
- Aged, Alzheimer Disease classification, Amyloid beta-Peptides cerebrospinal fluid, Area Under Curve, Biomarkers cerebrospinal fluid, Chitinase-3-Like Protein 1 cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, Cognitive Dysfunction classification, Cross-Sectional Studies, Diagnosis, Differential, Female, Frontotemporal Dementia cerebrospinal fluid, Frontotemporal Dementia classification, Humans, Male, Middle Aged, Neurofilament Proteins cerebrospinal fluid, Nuclear Proteins cerebrospinal fluid, Peptide Fragments cerebrospinal fluid, RNA-Binding Proteins, ROC Curve, Retrospective Studies, tau Proteins cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid
- Abstract
Introduction: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ
1-42 ], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation., Methods: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified., Results: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for distinguishing between FTD patients and HC (AUROC = 0.78)., Conclusions: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
27. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study.
- Author
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Dubois B, Epelbaum S, Nyasse F, Bakardjian H, Gagliardi G, Uspenskaya O, Houot M, Lista S, Cacciamani F, Potier MC, Bertrand A, Lamari F, Benali H, Mangin JF, Colliot O, Genthon R, Habert MO, and Hampel H
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease metabolism, Alzheimer Disease pathology, Alzheimer Disease psychology, Brain metabolism, Brain pathology, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuroimaging, Neuropsychological Tests, Positron-Emission Tomography, Risk Factors, Alzheimer Disease diagnostic imaging, Amyloid beta-Peptides metabolism, Brain diagnostic imaging, Cognition physiology
- Abstract
Background: Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease., Methods: The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on
18 F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on18 F-fluorodeoxyglucose (18 F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and18 F-FDG and18 F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type., Findings: From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1-8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid β deposition and the remainder did not. The amyloid β subgroups did not differ for any psychobehavioural, cognitive, actigraphy, and structural and functional neuroimaging results after adjustment for age, sex, and level of education More participants positive for amyloid β deposition had the APOE ε4 allele (33 [38%] vs 29 [13%], p<0·0001). Amyloid β1-42 concentration in CSF significantly correlated with mean18 F-florbetapir uptake at baseline (r=-0·62, p<0·0001) and the ratio of amyloid β1-42 to amyloid β1-40 (r=-0·61, p<0·0001), and identified amyloid β deposition status with high accuracy (mean area under the curve values 0·89, 95% CI 0·80-0·98 and 0·84, 0·72-0·96, respectively). No difference was seen in MMSE (28·3 [SD 2·0] vs 28·9 [1·2], p=0·16) and Clinical Dementia Rating scores (0·06 [0·2] vs 0·05 [0·3]; p=0·79) at 30 months (n=274) between participants positive or negative for amyloid β. Four participants (all positive for amyloid β deposition at baseline) progressed to prodromal Alzheimer's disease. They were older than other participants positive for amyloid β deposition at baseline (mean 80·2 years [SD 4·1] vs 76·8 years [SD 3·4]) and had greater18 F-florbetapir uptake at baseline (mean standard uptake value ratio 1·46 [SD 0·16] vs 1·02 [SD 0·20]), and more were carriers of the APOE ε4 allele (three [75%] of four vs 33 [39%] of 83). They also had mild executive dysfunction at baseline (mean FCSRT free recall score 21·25 [SD 2·75] vs 29·08 [5·44] and Frontal Assessment Battery total score 13·25 [1·50] vs 16·05 [1·68])., Interpretation: Brain β-amyloidosis alone did not predict progression to prodromal Alzheimer's disease within 30 months. Longer follow-up is needed to establish whether this finding remains consistent., Funding: Institut Hospitalo-Universitaire and Institut du Cerveau et de la Moelle Epinière (IHU-A-ICM), Ministry of Research, Fondation Plan Alzheimer, Pfizer, and Avid., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
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28. Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology.
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Hampel H, Toschi N, Babiloni C, Baldacci F, Black KL, Bokde ALW, Bun RS, Cacciola F, Cavedo E, Chiesa PA, Colliot O, Coman CM, Dubois B, Duggento A, Durrleman S, Ferretti MT, George N, Genthon R, Habert MO, Herholz K, Koronyo Y, Koronyo-Hamaoui M, Lamari F, Langevin T, Lehéricy S, Lorenceau J, Neri C, Nisticò R, Nyasse-Messene F, Ritchie C, Rossi S, Santarnecchi E, Sporns O, Verdooner SR, Vergallo A, Villain N, Younesi E, Garaci F, and Lista S
- Subjects
- Animals, Brain diagnostic imaging, Humans, Neurology, Neurophysiology, Systems Biology, Translational Research, Biomedical, Alzheimer Disease diagnosis, Alzheimer Disease therapy, Precision Medicine
- Abstract
The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
- Published
- 2018
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29. Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept.
- Author
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Epelbaum S, Genthon R, Cavedo E, Habert MO, Lamari F, Gagliardi G, Lista S, Teichmann M, Bakardjian H, Hampel H, and Dubois B
- Subjects
- Alzheimer Disease classification, Alzheimer Disease diagnosis, Biomarkers metabolism, Humans, Terminology as Topic, Alzheimer Disease metabolism, Prodromal Symptoms
- Abstract
Preclinical Alzheimer's disease (AD) is a relatively recent concept describing an entity characterized by the presence of a pathophysiological biomarker signature characteristic for AD in the absence of specific clinical symptoms. There is rising interest in the scientific community to define such an early target population mainly because of failures of all recent clinical trials despite evidence of biological effects on brain amyloidosis for some compounds. A conceptual framework has recently been proposed for this preclinical phase of AD. However, few data exist on this silent stage of AD. We performed a systematic review to investigate how the concept is defined across studies. The review highlights the substantial heterogeneity concerning the three main determinants of preclinical AD: "normal cognition," "cognitive decline," and "AD pathophysiological signature." We emphasize the need for a harmonized nomenclature of the preclinical AD concept and standardized population-based and case-control studies using unified operationalized criteria., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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30. Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.
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Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O'Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, and Jack CR Jr
- Subjects
- Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Animals, Brain diagnostic imaging, Disease Progression, Humans, Alzheimer Disease diagnosis, Alzheimer Disease physiopathology, Brain pathology
- Abstract
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations., (Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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31. Effect of ramipril on insulin sensitivity in obese patients. Time-course study of glucose infusion rate during euglycaemic hyperinsulinaemic clamp.
- Author
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Valensi P, Derobert E, Genthon R, and Riou JP
- Subjects
- Adult, Blood Pressure physiology, Cross-Over Studies, Double-Blind Method, Female, Glucose Clamp Technique, Humans, Infusions, Intravenous, Middle Aged, Oxidation-Reduction, Pilot Projects, Time Factors, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Insulin Resistance, Obesity metabolism, Ramipril therapeutic use
- Abstract
To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.
- Published
- 1996
32. [Comparative study, using a placebo, of the frequency of micturition after repeated administration of piretanide SR 6 mg/day (Eurelix) to healthy volunteers].
- Author
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Genthon R, Chassard D, Derobert E, Kabir M, and Lendresse P
- Subjects
- Adult, Diuretics administration & dosage, Double-Blind Method, Healthy Worker Effect, Humans, Male, Placebos, Sulfonamides administration & dosage, Urination Disorders epidemiology, Volunteers, Diuretics pharmacology, Sulfonamides pharmacology, Urination Disorders chemically induced
- Abstract
Thirty healthy volunteers received piretanide SR 6 mg/day (n = 15) or placebo (n = 15) in a 10-day double-blind parallel-group comparative trial. 24-h urine output was significantly greater with piretanide than with placebo on D1 (1919 +/- 434 ml and 1160 +/- 335 ml respectively, p = 0.001 one-sided) as on D10 (1563 +/- 538 ml and 1236 +/- 435 ml respectively, p = 0.04 one-sided). Nevertheless the evolution of urinary output from D1 to D10 was significantly different (p = 0.008): it remained stable with placebo but diminished with piretanide. The diuretic effect of piretanide was apparent with a supplementary miction between 8 a.m. and 4 p.m. both on D1 and D10. Between 4 p.m. and 8 a.m., the number of mictions was the same in both groups. Thus piretanide SR 6 mg has a mild effect on the number of mictions; it should not alter patients' well-being.
- Published
- 1995
33. Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.
- Author
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Genthon R
- Subjects
- Adult, Aged, Blood Pressure drug effects, Double-Blind Method, Drug Therapy, Combination, Drug Tolerance, Female, Hemodynamics, Humans, Hydrochlorothiazide administration & dosage, Hydrochlorothiazide adverse effects, Male, Middle Aged, Posture, Ramipril administration & dosage, Ramipril adverse effects, Hydrochlorothiazide therapeutic use, Hypertension drug therapy, Ramipril therapeutic use
- Abstract
In a double-blind, parallel-group multicentre study, the efficacy and safety of a fixed low-dose combination of ramipril 2.5 mg and hydrochlorothiazide (HCT) 12.5 mg was compared with each of the component drugs when given as monotherapy. After a four-week placebo run-in, patients were randomized to receive either ramipril 2.5 mg (n = 218) or HCT 12.5 mg (n = 220), or the fixed-dose combination of ramipril 2.5 mg and HCT 12.5 mg (n = 222), for a period of eight weeks. At the end of the study, in which 624 patients had completed treatment, it was found that the decrease in supine diastolic blood pressure (the main efficacy parameter) was greater in the ramipril-HCT combination group than in either the ramipril or the HCT monotherapy groups, the difference being statistically significant when compared with the HCT group (-14.3, -13.1 and -12.4 mm Hg, respectively). Reductions in standing DBP and supine and standing systolic blood pressure (SBP) were also greatest in the combination group. The incidence of adverse events was lower in the combination group than in either of the monotherapy groups, and there were no serious clinically significant laboratory abnormalities in the combination group.
- Published
- 1994
34. [Gerstmann-Sträussler-Scheinker disease. Pathologal and genetic study].
- Author
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Genthon R, Gray F, Salama J, Duyckaerts C, Belin C, Brucher JM, Baron H, and Delaporte P
- Subjects
- Amyloidosis pathology, Brain pathology, Cerebellum pathology, Creutzfeldt-Jakob Syndrome diagnosis, Diagnosis, Differential, Gerstmann-Straussler-Scheinker Disease genetics, Humans, Kuru diagnosis, Male, Middle Aged, Pedigree, Gerstmann-Straussler-Scheinker Disease pathology
- Abstract
Gerstmann-Sträussler-Scheinker's disease is a familial spongiform encephalopathy whose pathological hallmark is the existence--especially in the cerebellum--of numerous amyloid plaques. We report here the third clinicopathological case in a French family. Brain tissue from one of its members--initially described as familial Creutzfeldt-Jakob's disease--has been reported as successfully inoculated to monkeys. We present the currently accumulating data favouring the hypothesis of a common etiology for familial Creutzfeldt-Jakob's disease and Gerstmann-Sträussler-Scheinker's disease. The familial characteristics, resulting in different durations of incubation and evolution, could lead to different clinical and histological expressions.
- Published
- 1992
35. [Peripheral facial paralysis after dental anesthesia].
- Author
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Genthon R, Mas JL, Bouche P, and Derouesne C
- Subjects
- Humans, Male, Middle Aged, Anesthesia, Dental adverse effects, Anesthesia, Local adverse effects, Facial Paralysis etiology
- Published
- 1987
36. [Cerebrotendinous xanthomatosis. Apropos of a case using magnetic resonance study of the brain and nerve biopsy].
- Author
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Amiel H, Gherardi R, Kanaan HY, Buisson J, Genthon R, Zinszner J, Giroux C, Delaporte P, and Salama J
- Subjects
- Adult, Brain pathology, Brain Diseases diagnosis, Brain Diseases pathology, Humans, Male, Muscular Diseases diagnosis, Muscular Diseases pathology, Peripheral Nerves pathology, Xanthomatosis diagnosis, Xanthomatosis pathology, Brain Diseases genetics, Magnetic Resonance Imaging, Muscular Diseases genetics, Tendons, Xanthomatosis genetics
- Published
- 1989
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