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1. Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease

Author

Sylvain Lehmann, Susanna Schraen-Maschke, Luc Buée, Jean-Sébastien Vidal, Constance Delaby, Christophe Hirtz, Frédéric Blanc, Claire Paquet, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, Olivier Hanon, and for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Subjects
Alzheimer’s disease, Amyloid, BACE1, Cerebrospinal fluid, Neurodegeneration, Neurogranin, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Background Current AT(N) stratification for Alzheimer’s disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy. Methods This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Biomarkers levels were related to the AT(N) framework. (A) and (T) were defined in BALTAZAR with CSF Aβ42/40 ratio and pTau217 respectively, and in ADNI with amyloid and tau PET. (N) was defined using total CSF tau in both cohorts. Results As expected, CSF Aβ42 decreased progressively with the AD continuum going from the A-T-N- to the A + T + N + profile. On the other hand, Tau and pTau181 increased progressively with the disease. The final transition from A + T + N- to A + T + N + led to a sharp increase in Aβ38, Aβ42 and sAPP levels. Synaptic CSF biomarkers BACE1 and neurogranin, were lowest in the initial A + T-N- stage and increased with T + and N + . CSF pTau181 and total tau were closely related in both cohorts. Conclusions The early transition to an A + phenotype (A + T-N-) primarily impacts synaptic function. The appearance of T + and then N + is associated with a significant and progressive increase in pathological Alzheimer's disease biomarkers. Our main finding is that CSF pTau181 is an indicator of N + rather than T + , and that N + is associated with elevated levels of BACE1 protein and beta-amyloid peptides. This increase may potentially fuel the amyloid cascade in a positive feedback loop. Overall, our data provide further insights into understanding the interconnected pathological processes of amyloid, tau, and neurodegeneration underlying Alzheimer's disease.

Published
2024
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2. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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3. Cancer mortality and competing causes of death in older adults with cancer: A prospective, multicentre cohort study (ELCAPA‐19)

Author

Déborah Assouan, Elena Paillaud, Philippe Caillet, Amaury Broussier, Emmanuelle Kempf, Maxime Frelaut, Etienne Brain, Emmanuelle Lorisson, Clelia Chambraud, Sylvie Bastuji‐Garin, Olivier Hanon, Florence Canouï‐Poitrine, Marie Laurent, and Claudia Martinez‐Tapia

Subjects
cancer, cause of death, geriatric assessment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background In older patients with cancer, comorbidities compete with cancer for cause of death. The objectives were to evaluate cancer mortality and factors associated, according to metastatic status. Methods Between 2007 and 2014, patients with cancer aged ≥70 referred for pre‐therapeutic geriatric assessment (GA) were included through the ELCAPA prospective cohort study. The underlying cause of death was defined according to the International Classification of Diseases, 10th Revision. The World Health Organisation definition was used to categorise the cause of death as cancer versus another disease (e.g. cardiovascular disease, infectious disease, etc.) Competing risk models were used. Results Mean (SD) age of the 1445 included patients was 80.2 (5.8) and 48% were women. Most common tumour sites were colorectal (19%), breast (17%) and urinary (15%); 773 patients (49%) had metastases. After a 34‐month median follow‐up, 706 cancer deaths were observed among 843 deaths. The 6‐month and 3‐year cancer mortality rates (95% CI) were 12% (9–15) and 34% (29–38) for non‐metastatic patients and 43% (39–47) and 79% (75–82) for metastatic patients, respectively. Dependency in activities of daily living and comorbidities were associated with 6‐month and 3‐year cancer mortality in non‐metastatic (adjusted subhazard ratio [aSHR] = 1.68 [0.99–2.85] and 1.69 [1.16–2.45]; and 1.98 [1.08–3.63] and 3.38 [1.47–7.76], respectively) and metastatic patients (aSHR = 2.81 [2.01–3.93] and 2.95 [2.14–4.07]; and 1.63 [1.18–2.25] and 2.06 [1.39–3.05], respectively). Impaired Timed‐Get‐Up‐and‐Go test was associated with 6‐month and 3‐year cancer mortality in metastatic patients (aSHR = 1.5 [1.06–2.12] and 1.38 [1.06–1.81], respectively). Obesity was negatively associated with 3‐year cancer death in non‐metastatic (aSHR = 0.53 [0.29–0.97]) and metastatic patients (aSHR = 0.71 [0.51–1.00]). Conclusions The majority of older adults with cancer referred for pre‐therapeutic GA die from cancer. Geriatric parameters are independently associated with cancer mortality and should be considered for prognosis assessment, decision‐making and care.

Published
2023
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4. Correction: Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The 'MIKADO' study.

Author

George Pisica-Donose, Matthieu Piccoli, Bastien Genet, Stéphane Bouee, Stefan Berechet, Ion Berechet, Antonin Dacasa Cortes, Sabri Atsamena, Catherine Bayle, Mihai Badescu, François Catelain, Lynda Kermeche, Isabelle Merlier, Sahondranirina Rakotoniary, Valérie Savin, Ariane Vidal, Jean-Sébastien Vidal, and Olivier Hanon

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

Published
2024
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5. Practical management of frailty in older patients with heart failure

Author

Anne‐Sophie Boureau, Cédric Annweiler, Joël Belmin, Claire Bouleti, Mathieu Chacornac, Michel Chuzeville, Jean‐Philippe David, Patrick Jourdain, Pierre Krolak‐Salmon, Nicolas Lamblin, Marc Paccalin, Laurent Sebbag, and Olivier Hanon

Subjects
Heart failure, Frailty, Older patients, Practical management, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims The heart failure (HF) prognosis in older patients remains poor with a high 5‐years mortality rate more frequently attributed to noncardiovascular causes. The complex interplay between frailty and heart failure contribute to poor health outcomes of older adults with HF independently of ejection fraction. The aim of this position paper is to propose a practical management of frailty in older patients with heart failure. Methods A panel of multidisciplinary experts on behalf the Heart Failure Working Group of the French Society of Cardiology and on behalf French Society of Geriatrics and Gerontology conducted a systematic literature search on the interlink between frailty and HF, met to propose an early frailty screening by non‐geriatricians and to propose ways to implement management plan of frailty. Statements were agreed by expert consensus. Results Clinically relevant aspects of interlink between frailty and HF have been reported to identify the population eligible for screening and the most suitable screening test(s). The frailty screening program proposed focuses on frailty model defined by an accumulation of deficits including geriatric syndromes, comorbidities, for older patients with HF in different settings of care. The management plan of frailty includes optimization of HF pharmacological treatments and non‐surgical device treatment as well as optimization of a global patient‐centred biopsychosocial blended collaborative care pathway. Conclusion The current manuscript provides practical recommendations on how to screen and optimize frailty management in older patients with heart failure.

Published
2022
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6. Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Author

Leslie Grasset, Cécile Proust-Lima, Jean-François Mangin, Marie-Odile Habert, Bruno Dubois, Claire Paquet, Olivier Hanon, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Renaud David, Therese Jonveaux, Catherine Belin, Adrien Julian, Isabelle Rouch-Leroyer, Jérémie Pariente, Maxime Locatelli, Marie Chupin, Geneviève Chêne, Carole Dufouil, and on behalf of the Memento Cohort Study group

Subjects
Social factors, Lifestyle factors, Cognitive function, Brain markers, Pathology, Pathways, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer’s disease and related dementia (ADRD), and cognition. Methods The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. Results Participants’ mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β = − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD. Conclusions Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Published
2022
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7. Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The 'MIKADO' study.

Author

George Pisica-Donose, Matthieu Piccoli, Bastien Genet, Stéphane Bouee, Stefan Berechet, Ion Berechet, Antonin Dacasa Cortes, Sabri Atsamena, Catherine Bayle, Mihai Badescu, François Catelain, Lynda Kermeche, Isabelle Merlier, Sahondranirina Rakotoniary, Valérie Savin, Ariane Vidal, Jean-Sébastien Vidal, and Olivier Hanon

Subjects
Medicine, Science
Abstract

ObjectivesCurrently, two classes of oral anticoagulants are available in nursing home residents: vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). DOACs have a higher net clinical benefit than VKAs but DOACs are about 10 times more expensive than VKAs. The objective of our study was to assess and compare the overall costs of anti-coagulant strategy (VKA or DOAC), i.e., including drugs, laboratory costs and time spent in human capital (nurses and medical time) in nursing homes in France.MethodsThis was an observational, multicenter, prospective study including nine nursing homes in France. Among these nursing homes, 241 patients aged 75 years and older and treated with VKA (n = 140) or DOAC (n = 101) therapy accepted to participate in the study.ResultsDuring the 3-month follow-up period, the adjusted mean costs per patient were higher for VKA than DOACs for nurse care (€327 (57) vs. €154 (56), pConclusionOur study showed that in nursing homes despite a higher drug cost, DOAC therapy is associated with a lower total cost and less time used by nurses and physicians for drug monitoring when compared to VKA.

Published
2023
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8. National survey on the management of heart failure in individuals over 80 years of age in French geriatric care units

Author

Clémence Boully, Jean-Sébastien Vidal, Etienne Guibert, Fanny Nisrin Ghazali, Alain Pesce, Bérengère Beauplet, Jean-Dominique Roger, Isabelle Carrière, Boubacar Timbely, Houria Idiri, Jean-Pierre Constensoux, Anne-Marie Durocher, Delphine Dubail, Marc Fargier, Claude Jeandel, Gilles Berrut, Olivier Hanon, and on behalf of the SFGG study group

Subjects
Heart failure, Heart failure treatment, +80+years+old%22">Age > 80 years old, Geriatric settings, Left ventricular ejection fraction, Geriatrics, RC952-954.6
Abstract

Abstract Background To evaluate the prevalence and management of heart failure (HF) in very old patients in geriatric settings. Methods Members of the French Society of Geriatrics and Gerontology throughout France were invited to participate in a point prevalence survey and to include all patients ≥80 years old, hospitalized in geriatric settings, with HF (stable or decompensated) on June 18, 2012. General characteristics, presence of comorbidities, blood tests and medications were recorded. Results Among 7,197 patients in geriatric institution, prevalence of HF was 20.5% (n = 1,478): (27% in acute care, 24.2% in rehabilitation care and 18% in nursing home). Mean age was 88.2 (SD = 5.2) and Charlson co morbidity score was high (8.49 (SD = 2.21)). Left ventricular ejection fraction (LVEF) was available in 770 (52%) patients: 536 (69.6%) had a preserved LVEF (≥ 50%), 120 (15.6%) a reduced LVEF (

Published
2019
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9. Low Systolic Blood Pressure and Mortality in Elderly Patients After Acute Myocardial Infarction

Author

Basile Mouhat, Alain Putot, Olivier Hanon, Jean Christophe Eicher, Frédéric Chagué, Jean‐Claude Beer, Maud Maza, Marianne Zeller, and Yves Cottin

Subjects
acute myocardial infarction, blood pressure, cardiovascular mortality, elderly patients, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Optimal blood pressure in elderly patients after acute myocardial infarction is still a matter of debate. In a prospective observational study, we aimed to identify optimal systolic blood pressure during the 48 first hours after admission for acute myocardial infarction and its prognostic value for cardiovascular mortality. Methods and Results From the Observatoire des Infarctus de Côte d'Or survey, all consecutive patients aged >75 years admitted for an acute myocardial infarction in a coronary care unit from 2012 to 2015 and discharged alive were included (n=814). Exclusion criteria were in‐hospital death, cardiogenic shock, and end‐stage renal disease. Average systolic blood pressure (aSBP) values over the first 48 hours after admission were recorded, and the population was dichotomized into 2 groups: low aSBP group (

Published
2020
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10. 3.4 Micro- and Macro-Vascular Remodeling and Cognitive Function in Hypertension

Author

Antonio Gallo, Etienne Charpentier, Thomas Dietenbeck, Antoine Dufay, Alban Redheuil, Marie Chupin, Olivier Hanon, Xavier Girerd, and Nadjia Kachenoura

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Cerebral microvascular alterations and hypoperfusion have been associated to cognitive disorder and dementia. We hypothesized that there is a direct link between retinal arteriolar remodelling, as assessed non-invasively using adaptive optics, and cognitive cerebral impairment in hypertensive patients. Methods: Hypertensive patients over 65 years old with or without mild cognitive impairment were recruited. Each patient had a cognitive evaluation with MMSE; a study of retinal vasculature with adaptative optics RTX1® Camera to measure WT, internal diameter (ID), wall-to-lumen ratio (WLR) and arterio-venous ratio (AVR); an aortic, cerebral and carotid MRI to study cerebral volumes and white matter hyper-intensities (WMH) and carotid/aortic backward/forward flow (BF/FF) and distensibility. Correlations between retinal and cerebral, carotid and aortic remodelling were analysed. Results: 51 treated and controlled hypertensive patients, aged of 74 ± 5 years, 67% males, were able to achieve all exams. Among subjects with higher WLR, a significantly lower MMSE was found (p = 0.04). Eye-Brain: AVR and arteriolar ID coefficient of variation were inversely related to cerebral volumes (r = −0.61, p = 0.01 and r = −0.58, p = 0.02). Eye-Carotid: AVR and arteriolar ID coefficient of variation were directly and indirectly correlated with peak BF/FF, respectively (r = 0.47, p = 0.005; r = −0.39, p = 0.02). Eye-Aorta: WT and AVR were inversely correlated with ascending aorta distensibility (r = −0.48, p = 0.003; r = −0.47, p = 0.007). Conclusion: In elderly hypertensives, arteriolar retinal remodelling represents a potential marker of early cerebral atrophy, which might be linked to a cerebral microcirculation remodelling. This hypothesis is supported by the association between retinal vascular remodelling and impaired carotid flow and aortic elastic properties.

Published
2020
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11. Subjective cognitive and non‐cognitive complaints and brain MRI biomarkers in the MEMENTO cohort

Author

Virginie Dauphinot, Vincent Bouteloup, Jean‐François Mangin, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Olivier Hanon, Audrey Gabelle, Cédric Annweiler, Renaud David, Vincent Planche, Olivier Godefroy, Thérèse Rivasseau‐Jonveaux, Marie Chupin, Clara Fischer, Geneviève Chêne, Carole Dufouil, and Pierre Krolak‐Salmon

Subjects
magnetic resonance imaging, multi‐center cohort, preclinical AD, subjective health complaints, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Introduction Subjective cognitive complaints may be a signature of preclinical stage Alzheimer's disease. However, the link between subjective cognitive and non‐cognitive complaints and brain alterations remains unclear. Methods The relationship between cognitive and non‐cognitive complaints and brain biomarkers, measured by structural magnetic resonance imaging, was investigated in 2056 participants of the MEMENTO cohort of outpatients, who were dementia‐free at baseline. We assessed whether the cognitive status at inclusion or the presence of the apolipoprotein E gene variant (APOE) ε4 could modulate the association between the intensity of complaints and brain lesions. Results Smaller hippocampal volume was associated with higher memory complaints and discomfort in daily life. In APOE ε4 carriers, smaller whole‐brain white matter and gray matter volumes and gyrification indices in several regions of interest of the parietal and temporal lobes, in the entorhinal and the para‐hippocampal gyrus, were associated with higher memory complaint score. Conclusions The intensity of subjective complaints in not only memory but discomfort in daily life was associated with brain degeneration markers. The presence of APOE ε4 modulated the relationships between subjective memory complaints and brain alterations.

Published
2020
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12. Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Author

Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Jacques Hugon, Olivier Hanon, Jean-François Dartigues, Sandrine Harston, Audrey Gabelle, Mathieu Ceccaldi, Olivier Beauchet, Pierre Krolak-Salmon, Renaud David, Olivier Rouaud, Olivier Godefroy, Catherine Belin, Isabelle Rouch, Nicolas Auguste, David Wallon, Athanase Benetos, Jérémie Pariente, Marc Paccalin, Olivier Moreaud, Caroline Hommet, François Sellal, Claire Boutoleau-Bretonniére, Isabelle Jalenques, Armelle Gentric, Pierre Vandel, Chabha Azouani, Ludovic Fillon, Clara Fischer, Helen Savarieau, Gregory Operto, Hugo Bertin, Marie Chupin, Vincent Bouteloup, Marie-Odile Habert, Jean-François Mangin, Geneviève Chêne, and on behalf of the MEMENTO cohort Study Group

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

Abstract Background The natural history and disease mechanisms of Alzheimer’s disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. Methods In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR]

Published
2017
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13. Corrigendum: Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aß1−42, and Tau Proteins in Elderly Patients With Mild Cognitive Impairment

Author

Emmanuelle Duron, Jean-Sébastien Vidal, Dominique Grousselle, Audrey Gabelle, Sylvain Lehmann, Florence Pasquier, Stéphanie Bombois, Luc Buée, Bernadette Allinquant, Susanna Schraen-Maschke, Christiane Baret, Anne-Sophie Rigaud, Olivier Hanon, and Jacques Epelbaum

Subjects
somatostatin, neuropeptide Y, peptides Aß1−42, tau proteins, cerebrospinal fluid, mild cognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2019
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14. Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aβ1–42 and Tau Proteins in Elderly Patients With Mild Cognitive Impairment

Author

Emmanuelle Duron, Jean-Sébastien Vidal, Dominique Grousselle, Audrey Gabelle, Sylvain Lehmann, Florence Pasquier, Stéphanie Bombois, Luc Buée, Bernadette Allinquant, Susanna Schraen-Maschke, Christiane Baret, Anne-Sophie Rigaud, Olivier Hanon, and Jacques Epelbaum

Subjects
somatostatin, neuropeptide Y, peptides Aβ1–42, tau proteins, cerebrospinal fluid, mild cognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1–42; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer’s disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1–42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers.Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.

Published
2018
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15. Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: A feasibility study

Author

Claire Boutet, Marie Chupin, Stéphane Lehéricy, Linda Marrakchi-Kacem, Stéphane Epelbaum, Cyril Poupon, Christopher Wiggins, Alexandre Vignaud, Dominique Hasboun, Bénédicte Defontaines, Olivier Hanon, Bruno Dubois, Marie Sarazin, Lucie Hertz-Pannier, and Olivier Colliot

Subjects
Alzheimer's disease, Human 7 T MRI, Hippocampus, Hippocampal layers, Segmentation, Volumetry, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

In Alzheimer's disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmit–receive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p

Published
2014
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16. Patient-Reported Treatment Satisfaction with Rivaroxaban for Stroke Prevention in Atrial Fibrillation. A French Observational Study, the SAFARI Study.

Author

Olivier Hanon, Edouard Chaussade, Pierre Gueranger, Elise Gruson, Sabrina Bonan, and Alain Gay

Subjects
Medicine, Science
Abstract

For antithrombotic treatments, Patient Reported Outcomes (PRO) and patient satisfaction with treatment are essential data for physicians because of the strong relationship between patient satisfaction and adherence to treatment. The impact of rivaroxaban on patient satisfaction and quality of life was not sufficiently documented in phase III studies. There is a need for further data in this field especially in real life conditions.The SAFARI study is composed of patients with non-valvular atrial fibrillation (AF), previously treated with vitamin K antagonist (VKA) and switched to rivaroxaban. Patient satisfaction with anticoagulant therapy was measured by the Anti-Clot Treatment Scale (ACTS), a validated 15-item patient-reported scale including a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Satisfaction of medication was compared between baseline and 1, 3 and 6 months.Study population was composed of 405 patients. Mean age was 74.8 (standard deviation = 9.0) years and 63.0% were male. Mean CHA2DS2-VASc score was 3.4 (1.5) and mean HAS-BLED score was 2.9 (1.0). After 3 months of treatment with rivaroxaban, patient satisfaction improved compared with VKA: mean ACTS burdens scores significantly increased by 8.3 (8.9) points (p

Published
2016
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17. Vascular risk factors, cognitve decline, and dementia

Author

E Duron and Olivier Hanon

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

Published
2008

18. Comorbidities against quality control of VKA therapy in non-valvular atrial fibrillation: a French national cross-sectional study.

Author

Agnes Rouaud, Olivier Hanon, Anne-Sophie Boureau, Guillaume Chapelet, and Laure de Decker

Subjects
Medicine, Science
Abstract

Given the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.Determine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.Cross-sectional study.French geriatric care units nationwide.2164 patients aged 80 and over and treated with vitamin K antagonists.Comorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).An elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding.

Published
2015
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19. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Author

Valentina Escott-Price, Céline Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L DeStefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, United Kingdom Brain Expression Consortium, Andrew D Johnson, Agustin Ruiz, Marie-Thérèse Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimon, Alberto Lleo, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renee F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramirez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams, and Cardiovascular Health Study (CHS)

Subjects
Medicine, Science
Abstract

BACKGROUND:Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS:In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. SIGNIFICANCE:The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Published
2014
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20. Does cognitive function increase over time in the healthy elderly?

Author

Jocelyne de Rotrou, Ya-Huei Wu, Jean-Bernard Mabire, Florence Moulin, Laura W de Jong, Anne-Sophie Rigaud, Olivier Hanon, and Jean-Sébastien Vidal

Subjects
Medicine, Science
Abstract

In dementia screening, most studies have focused on early cognitive impairment by comparing patients suffering from mild dementia or mild cognitive impairment with normal subjects. Few studies have focused on modifications over time of the cognitive function in the healthy elderly. The objective of the present study was to analyze the cognitive function changes of two different samples, born > 15 years apart.A first sample of 204 cognitively normal participants was recruited in the memory clinic of Broca hospital between 1991 and 1997. A second sample of 177 cognitively normal participants was recruited in 2008-2009 in the same institution. Both samples were from the same districts of Paris and were assessed with the same neuropsychological test battery. Mean cognitive test scores were compared between 1991 and 2008 samples, between < 80 years old and ≥ 80 years old in 1991 and 2008 samples, and finally between subjects < 80 year old of 1991 sample and subjects ≥ 80 years old of the 2008 sample. Means were compared with T-tests stratified on gender, age-groups and educational level.Cognitive scores were significantly higher in the 2008 sample. Participants < 80 years old outperformed those ≥ 80 in both samples. However, participants < 80 years old in 1991 sample and subjects ≥ 80 in the 2008 sample, born on average in 1923, performed mostly identically.This study showed a significant increase of cognitive scores over time. Further, contemporary octogenarians in the later sample performed like septuagenarians in the former sample. These findings might be consistent with the increase in life expectancy and life span in good health. The study highlights the necessity to take into account factors which may contaminate and artificially inflate the age-related differences in favor of younger to the older adults.

Published
2013
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21. Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Author

Sylvain Lehmann, Susanna Schraen-Maschke, Jean-Sébastien Vidal, Constance Delaby, Frédéric Blanc, Claire Paquet, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, and Olivier Hanon

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

ObjectivesPlasma P-tau181 is an increasingly established diagnostic marker for Alzheimer’s disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level.MethodsThis study is ancillary to the prospective multicenter BALTAZAR cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to three years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay.ResultsAmong 476 MCI participants, 67% were Aβ+ at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 [SD 1.4] vs. 2.6 [SD 1.4] pg/mL) and in MCI that converted to dementia (3.8 [SD 1.5] vs. 2.9 [SD 1.4] pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and mini mental state examination (MMSE) improved predictive performance (AUC 0.691 to 0.744 for conversion and 0.786 to 0.849 for Aβ+). The Kaplan–Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank PConclusionsPlasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.What is already known on this topicThe clinical use of plasma phosphorylated tau 181 (P-tau181) for Alzheimer’s disease is being considered but further validation and study of confounding factors are still needed.What this study addsIn our large prospective cohort, P-tau181 predicts brain amyloidopathy and conversion to dementia in patients with mild cognitive impairment, but renal function significantly alters plasma levels and thus may induce diagnostic errors if not taken into account.How this study might affect research, practice or policyOur study suggests that measurement of creatinine or estimation of glomerular filtration rate, which are easy and standardizable ways to provide information on renal function, will contribute to optimal interpretation of plasma P-tau181 results in routine clinical practice.

Published
2023
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22. Blood pressure, antihypertensive drugs, and incident frailty: The Multidomain Alzheimer Preventive Trial (MAPT)

Author

Laure Rouch, Yves Rolland, Olivier Hanon, Jean-Sébastien Vidal, Philippe Cestac, Brigitte Sallerin, Sandrine Andrieu, Bruno Vellas, and Philipe De Souto Barreto

Subjects
Frailty, Alzheimer Disease, Hypertension, Humans, Obstetrics and Gynecology, Blood Pressure, tau Proteins, Antihypertensive Agents, General Biochemistry, Genetics and Molecular Biology, Aged
Abstract

To examine the association of (1) high and low blood pressure (BP) and (2) antihypertensive (AH) drug use with incident frailty.We conducted a secondary analysis of data from the Multidomain Alzheimer Preventive Trial (MAPT), in which 1394 non-frail community-dwelling participants aged ≥70 years were followed up for 5 years. BP was measured once at baseline in a lying position using a validated electronic device. High BP was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, and low BP as systolic BP ≤ 110 mm Hg and/or diastolic BP ≤ 70 mm Hg. AH drugs were assessed at baseline and classified according to the Anatomical Therapeutic Chemical (ATC) code.Incident frailty over the 5 years was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses.Low BP was associated with a greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p = 0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and those on two or more AH drugs were at the greatest risk of frailty. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p = 0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p = 0.22) was independently associated with incident frailty.Low BP could be used as a new marker for identifying older adults at higher risk of frailty.gov registration number: NCT00672685.

Published
2022
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25. Plasma Aβ42/Aβ40 ratio is independent of renal function

Author

Sylvain Lehmann, Susanna Schraen‐Maschke, Jean‐Sébastien Vidal, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, and Olivier Hanon

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2023
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26. Impact of a public open-access community-based physical activity and fall prevention program on physical performance in older adults

Author

Manuel Sanchez, Jean-Sébastien Vidal, Astrid Bichon, Camille Mairesse, Christiane Flouquet, Olivier Hanon, and Agathe Raynaud-Simon

Subjects
Public Health, Environmental and Occupational Health
Abstract

Background In older adults, physical activity (PA) is important in maintaining physical performance. Data on the effectiveness of public open-access community-based programs on physical performance and fall prevention are scarce. Methods Prospective observational controlled study in community centers providing an open-access public prevention program. Retirees aged ≥60 years who chose to participate in weekly PA workshops for 3 months were compared to those who chose the cognitive stimulation (CS) workshops. Collected data: handgrip strength, five times sit-to-stand, single-leg stance, Timed Up and Go tests, gait speed, short physical performance battery (SPPB) and frailty status at baseline (M0) and at 3 months (M3). The proportion of participants reporting a history of falls was assessed at baseline and using follow-up telephone interviews (F-Up). Results Two hundred eighty-eight participants (age 73.8 years, 87% women) were included. The sit-to-stand test, single-leg stance and SPPB scores improved significantly between M0 and M3 in both groups. A greater SPPB increase was observed in the PA than in the CS group (+0.39 vs. +0.32 points, P = 0.02) after adjustment for age, sex, number of sessions attended, fall history and SPPB at baseline. During F-Up (median 22 months), the proportion of participants reporting at least one fall decreased from 55% to 31% (P = 0.01) in the PA group and from 27% to 19% (P = 0.12) in the CS group. Conclusion In a public open-access community-based program participants improved physical performance and reduced fall incidence when participating in the PA or the CS workshops. Older adults may benefit most from multifaceted prevention programs.

Published
2023

28. Protective association of HLA‐DRB1 *04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences

Author

Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris E Jansen, Eric Yu, Aude Nicolas, Itziar de Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier‐Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D. Talyansky, Selina Marie Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Álvarez‐Martínez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo García‐Ribas, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Ling, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Shumpei Niida, Børge G. Nordestgaard, Goran Papenberg, Janne M. Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Eng‐King Tan, Thomas Tegos, Charlotte E. Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans R.J. Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Henrik Zetterberg, Kaj Blennow, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole Andreassen, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Ruth Frikke‐Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje M. van der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan‐Or, Jean‐Charles Lambert, Michael D Greicius, and Emmanuel Mignot

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022
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29. Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

Author

Jérémie, Lespinasse, Geneviève, Chêne, Jean-Francois, Mangin, Bruno, Dubois, Frederic, Blanc, Claire, Paquet, Olivier, Hanon, Vincent, Planche, Audrey, Gabelle, Mathieu, Ceccaldi, Cedric, Annweiler, Pierre, Krolak-Salmon, Olivier, Godefroy, David, Wallon, Mathilde, Sauvée, Sébastien, Bergeret, Marie, Chupin, Cécile, Proust-Lima, Carole, Dufouil, Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lariboisière-François Widal, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Bordeaux (UB), Centre Mémoire de Ressources et de Recherches [Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM), U708, Neuroepidemiology, Paris, France

Subjects
cognition, hypertension, Epidemiology, Health Policy, structural equation model, amyloid beta 42, hippocampal volume, cortical thickness, white matter hyperintensities, fluorodeoxyglucose positron emission tomography, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, mediation, tau, Neurology (clinical), Geriatrics and Gerontology, positron emission tomography amyloid, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Introduction: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood.Methods: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data.Results: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers.Discussion: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association.Highlights: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.

Published
2022
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30. Empagliflozin in the elderly

Author

Laure de Decker, Jean Noël Trochu, Bastien Genet, Anne Sophie Boureau, Gilles Berrut, and Olivier Hanon

Subjects
Glycosuria, medicine.medical_specialty, Type 2 diabetes, Glucosides, Internal medicine, Diabetes mellitus, medicine, Empagliflozin, Humans, Hypoglycemic Agents, Diabetic Nephropathies, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Biological Psychiatry, Aged, Reabsorption, business.industry, medicine.disease, Renal glucose reabsorption, Neuropsychology and Physiological Psychology, Diabetes Mellitus, Type 2, Renal physiology, Heart failure, Cardiology, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business
Abstract

Glucose and sodium tubular reabsorption inhibitors, or gliflozins, are a new therapeutic class. Their novel mechanism of action involves inhibition of a glucose and Na+ reabsorption co-transporter in the renal proximal tubule. They reduce blood glucose levels by reducing renal glucose reabsorption. They therefore cause glycosuria, which constitutes an energy loss and ultimately leads to a weight loss of around 2 to 3 kg. They reduce the sodium load and lower blood pressure. This class improves HbA1c by about 0.7%. Empagliflozin has been shown to reduce all-cause mortality in type 2 diabetic patients at high cardiovascular risk and to reduce episodes of cardiac decompensation and is nephroprotective in diabetic and non-diabetic subjects. Empagliflozin, like other gliflozins, does not induce hypoglycaemia as it does not directly stimulate insulin secretion. Due to the high prevalence of type 2 diabetes, heart failure and renal failure in the elderly, gliflozins will become part of geriatric prescriptions. Their advantages and use must be known, especially as their place will be extended to numerous indications in the field of chronic diseases.

Published
2021
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32. Apixaban versus other anticoagulants in patients with nonvalvular fibrillation: a comparison of all-cause and event-related costs in real-life setting in France

Author

Manon Belhassen, Olivier Hanon, Philippe Gabriel Steg, Isabelle Mahé, Mélanie Née, Flore Jacoud, Faustine Dalon, François-Emery Cotté, Dominique Guitard-Dehoux, Claire Marant-Micallef, Eric Van Ganse, and Nicolas Danchin

Subjects
Health Policy, Economics, Econometrics and Finance (miscellaneous)
Abstract

Objectives Compare costs associated with all-cause healthcare resource use (HCRU), stroke/systemic thromboembolism (STE) and major bleedings (MB) between patients with non-valvular atrial fibrillation (NVAF) initiating apixaban or other oral anticoagulants (OACs). Methods We performed a retrospective cohort study using the French healthcare claims database, including NVAF patients between 2014/01/01 and 2016/12/31, followed until 2016/12/31. We used 4 sub-cohorts of OAC-naive patients, respectively initiating apixaban, dabigatran, rivaroxaban or VKAs. We matched patients initiating apixaban with patients initiating each other OACs using 1:n propensity score matching. All-cause HCRU and event-related costs by OAC treatment were estimated and compared between matched patients using generalised-linear models with gamma-distribution and two-part models. Results There were 175,766 patients in the apixaban–VKA, 181,809 in the apixaban–rivaroxaban, and 42,490 in the apixaban–dabigatran matched cohorts. Patients initiating apixaban had significantly lower HCRU costs than patients initiating VKA (€1,105 vs. €1,578, p p p p p p = 0.07). Conclusions HCRU and most event-related costs were lower in patients initiating apixaban compared to other OACs. Apixaban may be cost-saving compared to VKAs, and significantly cheaper than other DOACs, although cost differences are limited.

Published
2022
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33. Visit-to-Visit Blood Pressure Variability and Incident Frailty in Older Adults

Author

Bruno Vellas, Jacques Amar, Philipe de Souto Barreto, P Cestac, Olivier Hanon, Yves Rolland, Laure Rouch, Jean-Sébastien Vidal, Sandrine Andrieu, and Mapt

Subjects
Male, Aging, medicine.medical_specialty, Mean arterial pressure, Blood Pressure, Risk Assessment, Alzheimer Disease, Risk Factors, Internal medicine, Ambulatory Care, medicine, Humans, Geriatric Assessment, Stroke, Aged, Proportional Hazards Models, Analysis of Variance, Frailty, Proportional hazards model, business.industry, Incidence, Hazard ratio, Blood Pressure Determination, medicine.disease, Confidence interval, Pulse pressure, Blood pressure, Cardiology, Female, France, Independent Living, Geriatrics and Gerontology, business, Body mass index
Abstract

This study aimed to determine whether visit-to-visit blood pressure (BP) variability (BPV) is associated with incident frailty. We included 1 394 nonfrail community-dwelling participants aged ≥70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations, including BP and frailty, over a 5-year follow-up period. Systolic BPV (SBPV), diastolic BPV (DBPV), mean arterial pressure variability (MAPV), and pulse pressure variability (PPV) were evaluated using standard deviation (SD), coefficient of variation (CV), average real variability, successive variation, variation independent of mean, and residual SD. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Higher SBPV was significantly associated with greater risk of frailty (1-SD increase of CV: hazard ratio [HR] = 1.18, 95% confidence interval [CI]: 1.02–1.36) after adjustment for demographics, systolic BP, antihypertensive drugs, body mass index, diabetes, ischemic heart disease, congestive heart failure, stroke, atrial fibrillation, MAPT randomization group, and frailty status. Similar results were observed with all indicators of variability. Higher PPV was associated with a greater risk of developing frailty over time (1-SD increase of CV: HR = 1.17, 95% CI: 1.01–1.35). DBPV and MAPV were not significantly associated with incident frailty. Higher SBPV and PPV were associated with greater risk of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that BP instability could be an early marker of frailty.

Published
2021
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34. Consensus of experts from the French Society of Geriatrics and Gerontology on the management of heart failure in very old subjects

Author

Joël Belmin, Olivier Hanon, Laure de Decker, Claude Jeandel, Fati Nourhashemi, Pierre Krolak-Salmon, Athanase Benetos, Marc Paccalin, and Philippe Chassagne

Subjects
Male, medicine.medical_specialty, Consensus, Frail Elderly, Health Status, Clinical Decision-Making, Management of heart failure, Cardiology, Comorbidity, 030204 cardiovascular system & hematology, Risk Assessment, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Prevalence, medicine, Risk of mortality, Humans, 030212 general & internal medicine, Aged, 80 and over, Heart Failure, Geriatrics, Polypharmacy, business.industry, Mortality rate, Palliative Care, Age Factors, Cardiovascular Agents, Recovery of Function, General Medicine, medicine.disease, Treatment Outcome, Heart failure, Emergency medicine, Quality of Life, Female, Cardiology and Cardiovascular Medicine, Heart failure with preserved ejection fraction, business
Abstract

The prevalence of heart failure increases with age. In France, the 1-year mortality rate is 35% in subjects aged 80-89 years with heart failure, and 50% after the age of 90 years. In octogenarians, heart failure is associated with high rates of cardiovascular and non-cardiovascular events, and is one of the main causes of hospitalization and disability. The prevalence of frailty increases in elderly subjects with heart failure, and the co-occurrence of heart failure and frailty increases the risk of mortality in patients with heart failure. In the elderly, the presence of frailty must be evaluated using a comprehensive geriatric assessment to manage geriatric syndromes, such as cognitive disorders, malnutrition, falls, depression, polypharmacy, disability and social isolation. The objective of heart failure therapy in octogenarians is to reduce symptoms, mortality and hospitalizations, but also to improve quality of life. In the absence of specific studies involving very old subjects, most recommendations are extrapolated from evidence-based data from younger populations. Overall, the epidemiological studies in patients with heart failure aged>80 years highlight the underprescription of recommended drugs. This underprescription may be related to comorbidity, a fear of side-effects and the lack of specific recommendations for drug prescription in heart failure with preserved ejection fraction, which is common in this very old population. The benefit/risk ratio related to heart failure treatment and comorbidity should be carefully weighed and reassessed on a regular basis. Consideration of disease prognosis according to factors that predict mortality can help to better define the care plan and promote palliative and supportive care when needed.

Published
2021
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35. Intérêt du traitement préventif par anticoagulant chez les patients âgés atteints de cancer sur les événements thromboemboliques veineux : conception et résultats à l’inclusion

Author

Olivier Hanon, Elena Paillaud, Aurélie Baudin, Sabrina Chaoui, Hélène Mabungu, Johanna Canovas, Lina Iratni, Axelle Histe, Prisca Lucas, Nadia Spiess, Marguerite Villebrun, Besma Saadaoui, Clelia Chambraud, Florence Rollot-Trad, Michael Bringuier, Amaury Broussier, and Florence Canoui-Poitrine

Subjects
Cardiology and Cardiovascular Medicine
Published
2023
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36. Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Author

Eloy Rodriguez-Rodríguez, Alfredo Ramirez, Laura Montrreal Navarro, Angel Carracedo, Adelina Orellana, Marta Marquié Sayagués, Pablo García González, Niccolo' Tesi, Raquel Puerta Fuentes, Per Selnes, and Olivier Hanon

Abstract

Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer’s disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8,074; replication n = 5,042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for amyloid beta 42 (Aβ42) and BIN1 for phosphorylated Tau (pTau). GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories (amyloid, astrocyte, processing & migration, and migration & motility) suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

Published
2022
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37. Estimation of the plasma volume status of elderly patients with acute decompensated heart failure using bedside clinical, biological, and ultrasound parameters

Author

Xenia Leahova‐Cerchez, Emmanuelle Berthelot, Bastien Genet, Olivier Hanon, and Patrick Jourdain

Subjects
Heart Failure, Male, Clinical Investigations, General Medicine, Peptide Fragments, Natriuretic Peptide, Brain, cardiovascular system, Humans, Female, Longitudinal Studies, Prospective Studies, Plasma Volume, Cardiology and Cardiovascular Medicine, Aged, Ultrasonography
Abstract

OBJECTIVE: Assessment of intravascular volume status to ensure optimization before hospital discharge could significantly reduce readmissions. It is difficult to evaluate congestion on clinical signs during an episode of acute heart failure (ADHF) in elderly patients. HYPOTHESIS: There is an association between various volume overload parameters in patients older than 75 years. METHODS: We performed a single‐center prospective longitudinal study of patients older than 75 years hospitalized for acute heart failure. We analyzed the association between congestion assessment based on clinical signs, inferior vena cava (IVC) diameter measured by ultrasound, biological evaluation with N terminal pro brain natriuretic peptide (NT‐proBNP), and estimated plasma volume (EPV) during decongestive therapy. We also monitored changes in renal function. RESULTS: Fifty consecutive ADHF patients (85.2 ± 5.9 years, 68% female) were included in the study. At admission, a dilated, noncompliant IVC was found in all patients. The strongest correlations between different parameters of volume overload estimation were found between IVC and jugular vein distention (r = .8; p

Published
2022

38. Abstract P011: Blood Pressure Postural Changes Variability Is Associated With Cognitive Decline: The S.ages Cohort

Author

Strumia Mathilde, Jean-Sébastien Vidal, Olivier Hanon, and Laure Rouch

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Over the past decade, higher blood pressure (BP) variability has been associated with cognitive decline (CD). To date, only one study investigated the specific impact of visit-to-visit BP postural changes variability on dementia but its association with cognition is still unknown. We aimed to investigate the association between BP postural changes variability and cognitive function in noninstitutionalized subjects aged ≥ 65 years. Methods: The S.AGES (Sujets Å;gés) cohort followed for three years noninstitutionalized subjects aged ≥ 65 years without major neurocognitive impairment at inclusion. At each visit, an orthostatic systolic BP (SBP) ratio was calculated using the formula (sitting SBP/standing SBP) x 100. An orthostatic diastolic BP ratio was computed using the same method. Subjects with a SBP ratio > 100% had sitting SBP > standing SBP. We assessed the visit-to-visit BP postural changes variability according to several indicators: standard deviation, coefficient of variation (CV), variation independent of mean, residual standard deviation, average real variability, and successive variation. Cognitive performances were evaluated using the Mini-Mental State Examination. Linear mixed models were used for the analyses. Results: We included 2,974 subjects (mean age 78 years, women 56%). After adjustment for age, sex, education, baseline body mass index, smoking, alcohol intake, atrial fibrillation, congestive heart failure, transient ischemic attack or stroke, coronary artery disease, type 2 diabetes, dyslipidemia, seated SBP/DBP and antihypertensive treatment, greater visit-to-visit systolic BP postural changes variability was significantly associated with CD over time (adjusted β [95% CI] = -0.17 [-0.29; -0.06], p= 0.004 for CV). Similar results were found for visit-to-visit diastolic BP postural changes variability (adjusted β [95% CI] = -0.14 [-0.25; -0.03], p= 0.017 for CV). Conclusion: Greater visit-to-visit BP postural changes variability was associated with CD. Further studies are needed to assess whether controlling orthostatic BP instability over time could be a promising interventional target to preserve cognition among older adults.

Published
2022
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39. Abstract P012: Orthostatic Hypo- And Hyper-tension Are Associated With Cognitive Decline: The S.ages Cohort

Author

Strumia Mathilde, Olivier Hanon, Jean-Sébastien Vidal, and Laure Rouch

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: The association between orthostatic hypotension (OHYPO) and cognition has reported conflicting results. Although orthostatic hypertension (OHYPER) is an emerging cardiovascular risk factor, only very few studies investigated its association with cognition. We aimed to assess the impact of OHYPO and OHYPER on cognitive performances in non-institutionalized subjects aged ≥ 65 years. Method: The S.AGES (Sujets Ågés) cohort followed for three years non-institutionalized subjects aged ≥ 65 years without major neurocognitive impairment at inclusion. OHYPO was defined as a decrease in systolic blood pressure (SBP) of at least 20 mmHg and/or diastolic blood pressure (DBP) of at least 10 mmHg from a sitting to a standing position. In contrast, OHYPER was defined as an increase in SBP of at least 20 mmHg and/or DBP of at least 10 mmHg under the same measurement conditions. Cognition was assessed using the Mini-Mental State Examination (MMSE). Linear mixed models were used for the analyses. Results: We included 3,170 subjects (mean age 78 years, 56% women). 209 (6.5%) had OHYPO at inclusion and 226 (7.1%) had OHYPER. Over time, MMSE was on average 0.5 points lower in patients with OHYPO compared to those without OHYPO or OHYPER (adjusted β [IC95%] = -0.52 [-0.97 ; -0.08], p=0.021) after adjustment for age, sex, education, baseline body mass index, smoking, alcohol intake, atrial fibrillation, congestive heart failure, transient ischemic attack or stroke, coronary artery disease, type 2 diabetes, dyslipidemia, seated SBP/DBP and antihypertensive treatment. Similarly, patients with OHYPER had, on average, poorer cognitive performances over time compared to those without pathological blood pressure (BP) postural changes (adjusted β [IC95%] = -0.54 [-0.98; -0.09], p = 0.017). Conclusion: Both OHYPO and OHYPER were associated with cognitive decline. Considering that BP postural changes are common in the elderly and easy to detect, orthostatic BP measurements could help identify patients with greater risk of cognitive impairment.

Published
2022
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40. Abstract P003: Blood Pressure, Antihypertensive Drugs, And Incident Frailty: The Multidomain Alzheimer Preventive Trial

Author

Laure Rouch, Yves Rolland, Olivier Hanon, Jean-Sébastien Vidal, Philippe CESTAC, SALLERIN brigitte, Sandrine Andrieu, Bruno Vellas, and Philipe de Souto Barreto

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Objectives: To examine the association of (1) high and low BP levels and (2) AH drug use with incident frailty. Study design: We conducted a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT). We included and followed-up for 5 years 1,394 non-frail community-dwelling participants aged ≥ 70 years. Main outcome measures: High BP was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and low BP as systolic BP ≤ 110 mmHg and/or diastolic BP ≤ 70 mmHg. AH drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Results: Low BP was associated with greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p=0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and 2 AH drugs or more were those having the greatest risk. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p=0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p=0.22) were independently associated with incident frailty. Conclusions: Low BP could be used as a new marker for identifying older adults at higher risk of frailty. AH medications in older adults with low BP should be continuously reviewed to assure that their potential benefits outweigh potential risks.

Published
2022
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41. Blood pressure control in patients with chronic kidney disease according to office and home blood pressures

Author

Olivier Jabourek, Club des jeunes hypertensiologues, Olivier Hanon, Jean-Pierre Fauvel, J. Ott, Y. Dimitrov, Jacques Fourcade, François Chantrel, Michel Ducher, Jean-Michel Achard, and Daniela Babici

Subjects
medicine.medical_specialty, Evening, Patients, Diastole, Renal function, Blood Pressure, 030204 cardiovascular system & hematology, Assessment and Diagnosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Renal Insufficiency, Chronic, Antihypertensive Agents, Morning, Advanced and Specialized Nursing, Proteinuria, business.industry, General Medicine, Blood Pressure Monitoring, Ambulatory, medicine.disease, Circadian Rhythm, Blood pressure, Hypertension, Ambulatory, medicine.symptom, Cardiology and Cardiovascular Medicine, business, circulatory and respiratory physiology, Kidney disease
Abstract

OBJECTIVES The aim of this study was to assess blood pressure (BP) control in patients with chronic kidney disease (CKD) according to office and home BP and to assess the prevalence of normal BP, white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and elevated BP. METHODS Patients with renal failure with or without proteinuria were included in this multicenter observational study. Office BP was first measured by the physician using a self-monitoring BP device (three automatic readings), then by the patient at home (morning and evening) over 3 consecutive days. WUCH was defined as a systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mmHg in the clinic and SBP/DBP

Published
2020
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42. Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation

Author

Ph. Gabriel Steg, S. Gollety, François-Emery Cotté, Bruno Falissard, Eric Van Ganse, Nicolas Danchin, Maeva Nolin, F. Jacoud, Olivier Hanon, F. Dalon, Isabelle Mahé, Manon Belhassen, and Cinira Lefevre

Subjects
safety, Adult, Male, medicine.medical_specialty, medicine.drug_class, Original Contributions, Embolism, Comparative safety, 030204 cardiovascular system & hematology, Clinical and Population Sciences, 03 medical and health sciences, 0302 clinical medicine, Rivaroxaban, Atrial Fibrillation, Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, Aged, Advanced and Specialized Nursing, business.industry, anticoagulant, Anticoagulant, Anticoagulants, Atrial fibrillation, Middle Aged, medicine.disease, mortality, Dabigatran, Stroke, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Apixaban, Warfarin, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Factor Xa Inhibitors, medicine.drug
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. Methods: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. Results: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS–matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40–0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63–0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81–1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56–0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97–1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78–1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. Conclusions: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Published
2020
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43. A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019)

Author

Farhad Pazan, Roland Hardt, Pedro Monteiro, Martin Hoffmeister, Olivier Hanon, Victor M. Gil, Ronan Collins, Freek W.A. Verheugt, Dieter Ropers, Martin Wehling, Terence J. Quinn, and Giuseppe Sergi

Subjects
Oral, Male, medicine.medical_specialty, Vitamin K, Pyridones, Consensus Development Conferences as Topic, Dabigatran, Phenprocoumon, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rivaroxaban, Edoxaban, Internal medicine, Atrial Fibrillation, medicine, Humans, Pharmacology (medical), Original Research Article, 030212 general & internal medicine, Administration, Oral, Aged, Anticoagulants, Europe, Female, Long-Term Care, Pyrazoles, Randomized Controlled Trials as Topic, Warfarin, Acenocoumarol, business.industry, Clinical trial, chemistry, Administration, Apixaban, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Introduction Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. Methods A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. Results A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. Conclusion OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age. Electronic supplementary material The online version of this article (10.1007/s40266-020-00771-0) contains supplementary material, which is available to authorized users.

Published
2020
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44. COVID-19 and cardiovascular diseases: viewpoint for older patients

Author

Laure de Decker, Olivier Hanon, Anne-Sophie Boureau, and Gilles Berrut

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Cardiovascular risk factors, Disease, medicine.disease_cause, Renin-Angiotensin System, Older patients, Pandemic, Humans, Medicine, Intensive care medicine, Pandemics, Biological Psychiatry, Coronavirus, business.industry, COVID-19, Cardiovascular Agents, Treatment Outcome, Neuropsychology and Physiological Psychology, Cardiovascular Diseases, Infectious disease (medical specialty), Cardiovascular agent, Neurology (clinical), Geriatrics and Gerontology, Coronavirus Infections, business
Abstract

The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.

Published
2020
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45. Insufficienza cardiaca della persona anziana

Author

Olivier Hanon, J Belmin, and P Friocourt

Subjects
03 medical and health sciences, 0302 clinical medicine, media_common.quotation_subject, 030212 general & internal medicine, Art, 030204 cardiovascular system & hematology, Humanities, media_common
Abstract

Riassunto L’insufficienza cardiaca (IC) e una patologia grave e frequente nelle persone anziane (PA), caratterizzata da una diagnosi spesso difficile, dall’importanza delle comorbilita, da una morbilita e mortalita elevate e da una maggiore frequenza di forme con frazione di eiezione sistolica conservata. Solo la gestione delle forme con frazione di eiezione alterata e ben codificata, sullo schema di quella degli adulti piu giovani: inibitori dell’enzima di conversione dell’angiotensina (ACE-inibitori), betabloccanti alle dosi massime tollerate, poi sacubitril-sartano (per sostituire l’ACE-inibitore), mentre gliantialdosteronici devono essere maneggiati con estrema cautela. Il ruolo della digossina e limitato. La ricerca di un’eziologia curabile (restringimento aortico, disturbo ritmico, sindrome da apnea notturna, ecc.), la vaccinazione contro l’influenza e lo pneumococco sono punti importanti. Il dosaggio dei diuretici dell’ansa deve essere adeguato allo stato di congestione. La gestione delle forme con frazione di eiezione conservata si basa sui diuretici dell’ansa durante le recidive e sul trattamento dell’ipertensione arteriosa come terapia di base. La valutazione geriatrica multidimensionale, la gestione delle comorbilita, l’educazione terapeutica e il monitoraggio rigoroso sono essenziali. Il ricorso a cure palliative e un’opzione da discutere nei casi piu avanzati.

Published
2020
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46. Insuficiencia cardíaca en la persona anciana

Author

P Friocourt, J Belmin, and Olivier Hanon

Subjects
03 medical and health sciences, 0302 clinical medicine, 030211 gastroenterology & hepatology, 030204 cardiovascular system & hematology
Abstract

Resumen La insuficiencia cardiaca (IC) es una afeccion grave y frecuente en las personas ancianas (PA); se caracteriza por tener un diagnostico que puede ser dificil, por la importancia de las comorbilidades, una morbilidad y una mortalidad elevadas, y por una mayor frecuencia de las formas con fraccion de eyeccion sistolica conservada. Unicamente el tratamiento de las formas con fraccion de eyeccion alterada esta bien establecido, basado en el esquema del de adultos mas jovenes: inhibidores de la enzima convertidora de la angiotensina (IECA), betabloqueantes en las dosis maximas toleradas, sacubitrilo-valsartan (en sustitucion del IECA) y antagonistas de la aldosterona, que deben manejarse con extrema prudencia. El uso de la digoxina es limitado. La busqueda de una etiologia curable (estenosis aortica, trastorno del ritmo, sindrome de apnea del sueno, etc.) asi como la vacunacion antigripal y antineumococica son medidas importantes. La posologia de los diureticos de asa debe adaptarse al estado de congestion. El tratamiento de las formas con eyeccion conservada se basa en el uso de diureticos de asa durante los episodios y en el tratamiento de la hipertension arterial como tratamiento de fondo. Son indispensables tambien la evaluacion geriatrica multidimensional, el tratamiento de las comorbilidades, la educacion terapeutica, asi como un seguimiento riguroso. En los casos mas avanzados, los cuidados paliativos son una posible opcion.

Published
2020
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47. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE‐ε4

Author

Yann Le Guen, Michael E Belloy, Benjamin Grenier‐Boley, Itziar de Rojas, Atahualpa Castillo, Iris E Jansen, Aude Nicolas, Céline Bellenguez, Carolina Dalmasso, Fahri Küçükali, Sarah J Eger, Victoria Álvarez‐Martínez, Beatrice Arosio, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimón, Delphine Daian, Antonio Daniele, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emrah Duzel, Daniela Galimberti, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Timo Grimmer, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Deckert Jurgen, Teemu Kuulasmaa, Aad van der Lugt, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Inez H.G.B. Ramakers, Katrine Laura Rasmussen, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Hilkka Soininen, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Thomas Tegos, Jesper Qvist Thomassen, Lucio Tremolizzo, Frans R.J. Verhey, Martin Vyhnalek, Jens Wiltfang, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M. van der Flier, Alfredo Ramirez, Ole Andreassen, Ruth Frikke‐Schmidt, Julie Williams, Agustin Ruiz, Jean‐Charles Lambert, and Michael D Greicius

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022

48. Protective association of HLA-DRB1*04 subtypes in neurodegenerative diseases implicates acetylated Tau PHF6 sequences

Author

Eloy Rodriguez-Rodríguez, Alfredo Ramirez, Laura Molina Porcel, Pablo García González, Jesper Qvist Thomassen, Michaël Belloy, Edna Grünblatt, Raquel Puerta Fuentes, Raquel Sanchez-Valle, and Olivier Hanon

Abstract

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s (PD) or Alzheimer’s (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2×10−13; AD: OR=0.91[0.89; 0.93]; p=1.8×10−22), and with a protective HLA association recently reported in amyotrophic lateral sclerosis (ALS). Hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03, and absent for HLA-DRB1*04:05. The same signal was associated with decreased neurofibrillary tangles (but not neuritic plaque density) in postmortem brains and was more strongly associated with Tau levels than Aβ42 levels in the cerebrospinal fluid. Finally, protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone Tau PHF6 sequence, but only when acetylated at K311, a modification central to aggregation. An HLA-DRB1*04-mediated adaptive immune response, potentially against Tau, decreases PD, AD and ALS risk, offering the possibility of new therapeutic avenues.

Published
2021
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49. Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study

Author

Nicolas Danchin, Gabriel Steg, Isabelle Mahé, Olivier Hanon, Flore Jacoud, Maëva Nolin, Faustine Dalon, François-Emery Cotte, Sabrina Gollety, Eric Van Ganse, and Manon Belhassen

Subjects
Stroke, Rivaroxaban, Atrial Fibrillation, Humans, Anticoagulants, Administration, Oral, General Medicine, Cardiology and Cardiovascular Medicine, Dabigatran, Retrospective Studies
Abstract

Direct oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation.This study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF.Within the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models.In a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR=0.63, 95%CI=[0.62-0.64]), rivaroxaban (HR=0.71, 95%CI=[0.70-0.73]), and dabigatran (HR=0.60, 95%CI=[0.59-0.62]).In this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.

Published
2021

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