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Obstructive Sleep Apnea and Hypertension with Longitudinal β-Amyloid Burden and Cognitive Changes

Bubu, Omonigho M; Kaur, Sonya S; Mbah, Alfred K; Umasabor-Bubu, Ogie Q; Ramos-Cejudo, Jaime; Debure, Ludovic; Mullins, Anna E; Parekh, Ankit; Kam, Korey; Osakwe, Zainab T; Williams, Ellita T; Turner, Arlener D; Glodzik, Lidia; Rapoport, David M; Ogedegbe, Gbenga; Fieremans, Els; de Leon, Mony J; Ayappa, Indu; Jean-Louis, Girardin; Masurkar, Arjun V; Varga, Andrew W; Osorio, Ricardo S
PMID: 35550019
ISSN: 1535-4970
CID: 5213082

Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Frontera, Jennifer A; Boutajangout, Allal; Masurkar, Arjun V; Betensky, Rebecca A; Ge, Yulin; Vedvyas, Alok; Debure, Ludovic; Moreira, Andre; Lewis, Ariane; Huang, Joshua; Thawani, Sujata; Balcer, Laura; Galetta, Steven; Wisniewski, Thomas
INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
PMID: 35023610
ISSN: 1552-5279
CID: 5116752

New insights into the genetic etiology of Alzheimer's disease and related dementias

Bellenguez, Céline; Küçükali, Fahri; Jansen, Iris E; Kleineidam, Luca; Moreno-Grau, Sonia; Amin, Najaf; Naj, Adam C; Campos-Martin, Rafael; Grenier-Boley, Benjamin; Andrade, Victor; Holmans, Peter A; Boland, Anne; Damotte, Vincent; van der Lee, Sven J; Costa, Marcos R; Kuulasmaa, Teemu; Yang, Qiong; de Rojas, Itziar; Bis, Joshua C; Yaqub, Amber; Prokic, Ivana; Chapuis, Julien; Ahmad, Shahzad; Giedraitis, Vilmantas; Aarsland, Dag; Garcia-Gonzalez, Pablo; Abdelnour, Carla; Alarcón-Martín, Emilio; Alcolea, Daniel; Alegret, Montserrat; Alvarez, Ignacio; Álvarez, Victoria; Armstrong, Nicola J; Tsolaki, Anthoula; Antúnez, Carmen; Appollonio, Ildebrando; Arcaro, Marina; Archetti, Silvana; Pastor, Alfonso Arias; Arosio, Beatrice; Athanasiu, Lavinia; Bailly, Henri; Banaj, Nerisa; Baquero, Miquel; Barral, Sandra; Beiser, Alexa; Pastor, Ana Belén; Below, Jennifer E; Benchek, Penelope; Benussi, Luisa; Berr, Claudine; Besse, Céline; Bessi, Valentina; Binetti, Giuliano; Bizarro, Alessandra; Blesa, Rafael; Boada, Mercè; Boerwinkle, Eric; Borroni, Barbara; Boschi, Silvia; Bossù, Paola; BrÃ¥then, Geir; Bressler, Jan; Bresner, Catherine; Brodaty, Henry; Brookes, Keeley J; Brusco, Luis Ignacio; Buiza-Rueda, Dolores; Bûrger, Katharina; Burholt, Vanessa; Bush, William S; Calero, Miguel; Cantwell, Laura B; Chene, Geneviève; Chung, Jaeyoon; Cuccaro, Michael L; Carracedo, Ángel; Cecchetti, Roberta; Cervera-Carles, Laura; Charbonnier, Camille; Chen, Hung-Hsin; Chillotti, Caterina; Ciccone, Simona; Claassen, Jurgen A H R; Clark, Christopher; Conti, Elisa; Corma-Gómez, Anaïs; Costantini, Emanuele; Custodero, Carlo; Daian, Delphine; Dalmasso, Maria Carolina; Daniele, Antonio; Dardiotis, Efthimios; Dartigues, Jean-François; de Deyn, Peter Paul; de Paiva Lopes, Katia; de Witte, Lot D; Debette, Stéphanie; Deckert, Jürgen; Del Ser, Teodoro; Denning, Nicola; DeStefano, Anita; Dichgans, Martin; Diehl-Schmid, Janine; Diez-Fairen, Mónica; Rossi, Paolo Dionigi; Djurovic, Srdjan; Duron, Emmanuelle; Düzel, Emrah; Dufouil, Carole; Eiriksdottir, Gudny; Engelborghs, Sebastiaan; Escott-Price, Valentina; Espinosa, Ana; Ewers, Michael; Faber, Kelley M; Fabrizio, Tagliavini; Nielsen, Sune Fallgaard; Fardo, David W; Farotti, Lucia; Fenoglio, Chiara; Fernández-Fuertes, Marta; Ferrari, Raffaele; Ferreira, Catarina B; Ferri, Evelyn; Fin, Bertrand; Fischer, Peter; Fladby, Tormod; Fließbach, Klaus; Fongang, Bernard; Fornage, Myriam; Fortea, Juan; Foroud, Tatiana M; Fostinelli, Silvia; Fox, Nick C; Franco-Macías, Emlio; Bullido, María J; Frank-García, Ana; Froelich, Lutz; Fulton-Howard, Brian; Galimberti, Daniela; García-Alberca, Jose Maria; García-González, Pablo; Garcia-Madrona, Sebastian; Garcia-Ribas, Guillermo; Ghidoni, Roberta; Giegling, Ina; Giorgio, Giaccone; Goate, Alison M; Goldhardt, Oliver; Gomez-Fonseca, Duber; González-Pérez, Antonio; Graff, Caroline; Grande, Giulia; Green, Emma; Grimmer, Timo; Grünblatt, Edna; Grunin, Michelle; Gudnason, Vilmundur; Guetta-Baranes, Tamar; Haapasalo, Annakaisa; Hadjigeorgiou, Georgios; Haines, Jonathan L; Hamilton-Nelson, Kara L; Hampel, Harald; Hanon, Olivier; Hardy, John; Hartmann, Annette M; Hausner, Lucrezia; Harwood, Janet; Heilmann-Heimbach, Stefanie; Helisalmi, Seppo; Heneka, Michael T; Hernández, Isabel; Herrmann, Martin J; Hoffmann, Per; Holmes, Clive; Holstege, Henne; Vilas, Raquel Huerto; Hulsman, Marc; Humphrey, Jack; Biessels, Geert Jan; Jian, Xueqiu; Johansson, Charlotte; Jun, Gyungah R; Kastumata, Yuriko; Kauwe, John; Kehoe, Patrick G; Kilander, Lena; StÃ¥hlbom, Anne Kinhult; Kivipelto, Miia; Koivisto, Anne; Kornhuber, Johannes; Kosmidis, Mary H; Kukull, Walter A; Kuksa, Pavel P; Kunkle, Brian W; Kuzma, Amanda B; Lage, Carmen; Laukka, Erika J; Launer, Lenore; Lauria, Alessandra; Lee, Chien-Yueh; Lehtisalo, Jenni; Lerch, Ondrej; Lleó, Alberto; Longstreth, William; Lopez, Oscar; de Munain, Adolfo Lopez; Love, Seth; Löwemark, Malin; Luckcuck, Lauren; Lunetta, Kathryn L; Ma, Yiyi; Macías, Juan; MacLeod, Catherine A; Maier, Wolfgang; Mangialasche, Francesca; Spallazzi, Marco; Marquié, Marta; Marshall, Rachel; Martin, Eden R; Montes, Angel Martín; Rodríguez, Carmen Martínez; Masullo, Carlo; Mayeux, Richard; Mead, Simon; Mecocci, Patrizia; Medina, Miguel; Meggy, Alun; Mehrabian, Shima; Mendoza, Silvia; Menéndez-González, Manuel; Mir, Pablo; Moebus, Susanne; Mol, Merel; Molina-Porcel, Laura; Montrreal, Laura; Morelli, Laura; Moreno, Fermin; Morgan, Kevin; Mosley, Thomas; Nöthen, Markus M; Muchnik, Carolina; Mukherjee, Shubhabrata; Nacmias, Benedetta; Ngandu, Tiia; Nicolas, Gael; Nordestgaard, Børge G; Olaso, Robert; Orellana, Adelina; Orsini, Michela; Ortega, Gemma; Padovani, Alessandro; Paolo, Caffarra; Papenberg, Goran; Parnetti, Lucilla; Pasquier, Florence; Pastor, Pau; Peloso, Gina; Pérez-Cordón, Alba; Pérez-Tur, Jordi; Pericard, Pierre; Peters, Oliver; Pijnenburg, Yolande A L; Pineda, Juan A; Piñol-Ripoll, Gerard; Pisanu, Claudia; Polak, Thomas; Popp, Julius; Posthuma, Danielle; Priller, Josef; Puerta, Raquel; Quenez, Olivier; Quintela, Inés; Thomassen, Jesper Qvist; Rábano, Alberto; Rainero, Innocenzo; Rajabli, Farid; Ramakers, Inez; Real, Luis M; Reinders, Marcel J T; Reitz, Christiane; Reyes-Dumeyer, Dolly; Ridge, Perry; Riedel-Heller, Steffi; Riederer, Peter; Roberto, Natalia; Rodriguez-Rodriguez, Eloy; Rongve, Arvid; Allende, Irene Rosas; Rosende-Roca, Maitée; Royo, Jose Luis; Rubino, Elisa; Rujescu, Dan; Sáez, María Eugenia; Sakka, Paraskevi; Saltvedt, Ingvild; Sanabria, Ángela; Sánchez-Arjona, María Bernal; Sanchez-Garcia, Florentino; Juan, Pascual Sánchez; Sánchez-Valle, Raquel; Sando, Sigrid B; Sarnowski, Chloé; Satizabal, Claudia L; Scamosci, Michela; Scarmeas, Nikolaos; Scarpini, Elio; Scheltens, Philip; Scherbaum, Norbert; Scherer, Martin; Schmid, Matthias; Schneider, Anja; Schott, Jonathan M; Selbæk, Geir; Seripa, Davide; Serrano, Manuel; Sha, Jin; Shadrin, Alexey A; Skrobot, Olivia; Slifer, Susan; Snijders, Gijsje J L; Soininen, Hilkka; Solfrizzi, Vincenzo; Solomon, Alina; Song, Yeunjoo; Sorbi, Sandro; Sotolongo-Grau, Oscar; Spalletta, Gianfranco; Spottke, Annika; Squassina, Alessio; Stordal, Eystein; Tartan, Juan Pablo; Tárraga, Lluís; Tesí, Niccolo; Thalamuthu, Anbupalam; Thomas, Tegos; Tosto, Giuseppe; Traykov, Latchezar; Tremolizzo, Lucio; Tybjærg-Hansen, Anne; Uitterlinden, Andre; Ullgren, Abbe; Ulstein, Ingun; Valero, Sergi; Valladares, Otto; Broeckhoven, Christine Van; Vance, Jeffery; Vardarajan, Badri N; van der Lugt, Aad; Dongen, Jasper Van; van Rooij, Jeroen; van Swieten, John; Vandenberghe, Rik; Verhey, Frans; Vidal, Jean-Sébastien; Vogelgsang, Jonathan; Vyhnalek, Martin; Wagner, Michael; Wallon, David; Wang, Li-San; Wang, Ruiqi; Weinhold, Leonie; Wiltfang, Jens; Windle, Gill; Woods, Bob; Yannakoulia, Mary; Zare, Habil; Zhao, Yi; Zhang, Xiaoling; Zhu, Congcong; Zulaica, Miren; Farrer, Lindsay A; Psaty, Bruce M; Ghanbari, Mohsen; Raj, Towfique; Sachdev, Perminder; Mather, Karen; Jessen, Frank; Ikram, M Arfan; de Mendonça, Alexandre; Hort, Jakub; Tsolaki, Magda; Pericak-Vance, Margaret A; Amouyel, Philippe; Williams, Julie; Frikke-Schmidt, Ruth; Clarimon, Jordi; Deleuze, Jean-François; Rossi, Giacomina; Seshadri, Sudha; Andreassen, Ole A; Ingelsson, Martin; Hiltunen, Mikko; Sleegers, Kristel; Schellenberg, Gerard D; van Duijn, Cornelia M; Sims, Rebecca; van der Flier, Wiesje M; Ruiz, Agustín; Ramirez, Alfredo; Lambert, Jean-Charles; Laczo, Jan; Matoska, Vaclav; Serpente, Maria; Assogna, Francesca; Piras, Fabrizio; Piras, Federica; Ciullo, Valentina; Shofany, Jacob; Ferrarese, Carlo; Andreoni, Simona; Sala, Gessica; Zoia, Chiara Paola; Zompo, Maria Del; Benussi, Alberto; Bastiani, Patrizia; Takalo, Mari; Natunen, Teemu; Laatikainen, Tiina; Tuomilehto, Jaakko; Antikainen, Riitta; Strandberg, Timo; Lindström, Jaana; Peltonen, Markku; Abraham, Richard; Al-Chalabi, Ammar; Bass, Nicholas J; Brayne, Carol; Brown, Kristelle S; Collinge, John; Craig, David; Deloukas, Pangiotis; Fox, Nick; Gerrish, Amy; Gill, Michael; Gwilliam, Rhian; Harold, Denise; Hollingworth, Paul; Johnston, Jarret A; Jones, Lesley; Lawlor, Brian; Livingston, Gill; Lovestone, Simon; Lupton, Michelle; Lynch, Aoibhinn; Mann, David; McGuinness, Bernadette; McQuillin, Andrew; O'Donovan, Michael C; Owen, Michael J; Passmore, Peter; Powell, John F; Proitsi, Petra; Rossor, Martin; Shaw, Christopher E; Smith, A David; Gurling, Hugh; Todd, Stephen; Mummery, Catherine; Ryan, Nathalie; Lacidogna, Giordano; Adarmes-Gómez, Ad; Mauleón, Ana; Pancho, Ana; Gailhajenet, Anna; Lafuente, Asunción; Macias-García, D; Martín, Elvira; Pelejà, Esther; Carrillo, F; Merlín, Isabel Sastre; Garrote-Espina, L; Vargas, Liliana; Carrion-Claro, M; Marín, M; Labrador, Ma; Buendia, Mar; Alonso, María Dolores; Guitart, Marina; Moreno, Mariona; Ibarria, Marta; Periñán, Mt; Aguilera, Nuria; Gómez-Garre, P; Cañabate, Pilar; Escuela, R; Pineda-Sánchez, R; Vigo-Ortega, R; Jesús, S; Preckler, Silvia; Rodrigo-Herrero, Silvia; Diego, Susana; Vacca, Alessandro; Roveta, Fausto; Salvadori, Nicola; Chipi, Elena; Boecker, Henning; Laske, Christoph; Perneczky, Robert; Anastasiou, Costas; Janowitz, Daniel; Malik, Rainer; Anastasiou, Anna; Parveen, Kayenat; Lage, Carmen; López-García, Sara; Antonell, Anna; Mihova, Kalina Yonkova; Belezhanska, Diyana; Weber, Heike; Kochen, Silvia; Solis, Patricia; Medel, Nancy; Lisso, Julieta; Sevillano, Zulma; Politis, Daniel G; Cores, Valeria; Cuesta, Carolina; Ortiz, Cecilia; Bacha, Juan Ignacio; Rios, Mario; Saenz, Aldo; Abalos, Mariana Sanchez; Kohler, Eduardo; Palacio, Dana Lis; Etchepareborda, Ignacio; Kohler, Matias; Novack, Gisela; Prestia, Federico Ariel; Galeano, Pablo; Castaño, Eduardo M; Germani, Sandra; Toso, Carlos Reyes; Rojo, Matias; Ingino, Carlos; Mangone, Carlos; Rubinsztein, David C; Teipel, Stefan; Fievet, Nathalie; Deramerourt, Vincent; Forsell, Charlotte; Thonberg, Håkan; Bjerke, Maria; Roeck, Ellen De; Martínez-Larrad, María Teresa; Olivar, Natividad; Aguilera, Nuria; Cano, Amanda; Cañabate, Pilar; Macias, Juan; Maroñas, Olalla; Nuñez-Llaves, Raúl; Olivé, Clàudia; Pelejá, Ester; Adarmes-Gómez, Astrid D; Alonso, María Dolores; Amer-Ferrer, Guillermo; Antequera, Martirio; Burguera, Juan Andrés; Carrillo, Fátima; Carrión-Claro, Mario; Casajeros, María José; Martinez de Pancorbo, Marian; Escuela, Rocío; Garrote-Espina, Lorena; Gómez-Garre, Pilar; Hevilla, Saray; Jesús, Silvia; Espinosa, Miguel Angel Labrador; Legaz, Agustina; López-García, Sara; Macias-García, Daniel; Manzanares, Salvadora; Marín, Marta; Marín-Muñoz, Juan; Marín, Tamara; Martínez, Begoña; Martínez, Victoriana; Martínez-Lage Álvarez, Pablo; Iriarte, Maite Mendioroz; Periñán-Tocino, María Teresa; Pineda-Sánchez, Rocío; Real de Asúa, Diego; Rodrigo, Silvia; Sastre, Isabel; Vicente, Maria Pilar; Vigo-Ortega, Rosario; Vivancos, Liliana; Epelbaum, Jacques; Hannequin, Didier; Campion, Dominique; Deramecourt, Vincent; Tzourio, Christophe; Brice, Alexis; Dubois, Bruno; Williams, Amy; Thomas, Charlene; Davies, Chloe; Nash, William; Dowzell, Kimberley; Morales, Atahualpa Castillo; Bernardo-Harrington, Mateus; Turton, James; Lord, Jenny; Brown, Kristelle; Vardy, Emma; Fisher, Elizabeth; Warren, Jason D; Rossor, Martin; Ryan, Natalie S; Guerreiro, Rita; Uphill, James; Bass, Nick; Heun, Reinhard; Kölsch, Heike; Schürmann, Britta; Lacour, André; Herold, Christine; Johnston, Janet A; Passmore, Peter; Powell, John; Patel, Yogen; Hodges, Angela; Becker, Tim; Warden, Donald; Wilcock, Gordon; Clarke, Robert; Deloukas, Panagiotis; Ben-Shlomo, Yoav; Hooper, Nigel M; Pickering-Brown, Stuart; Sussams, Rebecca; Warner, Nick; Bayer, Anthony; Heuser, Isabella; Drichel, Dmitriy; Klopp, Norman; Mayhaus, Manuel; Riemenschneider, Matthias; Pinchler, Sabrina; Feulner, Thomas; Gu, Wei; van den Bussche, Hendrik; Hüll, Michael; Frölich, Lutz; Wichmann, H-Erich; Jöckel, Karl-Heinz; O'Donovan, Michael; Owen, Michael; Bahrami, Shahram; Bosnes, Ingunn; Selnes, Per; Bergh, Sverre; Palotie, Aarno; Daly, Mark; Jacob, Howard; Matakidou, Athena; Runz, Heiko; John, Sally; Plenge, Robert; McCarthy, Mark; Hunkapiller, Julie; Ehm, Meg; Waterworth, Dawn; Fox, Caroline; Malarstig, Anders; Klinger, Kathy; Call, Kathy; Behrens, Tim; Loerch, Patrick; Mäkelä, Tomi; Kaprio, Jaakko; Virolainen, Petri; Pulkki, Kari; Kilpi, Terhi; Perola, Markus; Partanen, Jukka; Pitkäranta, Anne; Kaarteenaho, Riitta; Vainio, Seppo; Turpeinen, Miia; Serpi, Raisa; Laitinen, Tarja; Mäkelä, Johanna; Kosma, Veli-Matti; Kujala, Urho; Tuovila, Outi; Hendolin, Minna; Pakkanen, Raimo; Waring, Jeff; Riley-Gillis, Bridget; Liu, Jimmy; Biswas, Shameek; Diogo, Dorothee; Marshall, Catherine; Hu, Xinli; Gossel, Matthias; Graham, Robert; Cummings, Beryl; Ripatti, Samuli; Schleutker, Johanna; Arvas, Mikko; Carpén, Olli; Hinttala, Reetta; Kettunen, Johannes; Mannermaa, Arto; Laukkanen, Jari; Julkunen, Valtteri; Remes, Anne; Kälviäinen, Reetta; Peltola, Jukka; Tienari, Pentti; Rinne, Juha; Ziemann, Adam; Waring, Jeffrey; Esmaeeli, Sahar; Smaoui, Nizar; Lehtonen, Anne; Eaton, Susan; Lahdenperä, Sanni; van Adelsberg, Janet; Michon, John; Kerchner, Geoff; Bowers, Natalie; Teng, Edmond; Eicher, John; Mehta, Vinay; Gormley, Padhraig; Linden, Kari; Whelan, Christopher; Xu, Fanli; Pulford, David; Färkkilä, Martti; Pikkarainen, Sampsa; Jussila, Airi; Blomster, Timo; Kiviniemi, Mikko; Voutilainen, Markku; Georgantas, Bob; Heap, Graham; Rahimov, Fedik; Usiskin, Keith; Lu, Tim; Oh, Danny; Kalpala, Kirsi; Miller, Melissa; McCarthy, Linda; Eklund, Kari; Palomäki, Antti; Isomäki, Pia; Pirilä, Laura; Kaipiainen-Seppänen, Oili; Huhtakangas, Johanna; Lertratanakul, Apinya; Hochfeld, Marla; Bing, Nan; Gordillo, Jorge Esparza; Mars, Nina; Pelkonen, Margit; Kauppi, Paula; Kankaanranta, Hannu; Harju, Terttu; Close, David; Greenberg, Steven; Chen, Hubert; Betts, Jo; Ghosh, Soumitra; Salomaa, Veikko; Niiranen, Teemu; Juonala, Markus; Metsärinne, Kaj; Kähönen, Mika; Junttila, Juhani; Laakso, Markku; Pihlajamäki, Jussi; Sinisalo, Juha; Taskinen, Marja-Riitta; Tuomi, Tiinamaija; Challis, Ben; Peterson, Andrew; Chu, Audrey; Parkkinen, Jaakko; Muslin, Anthony; Joensuu, Heikki; Meretoja, Tuomo; Aaltonen, Lauri; Mattson, Johanna; Auranen, Annika; Karihtala, Peeter; Kauppila, Saila; Auvinen, Päivi; Elenius, Klaus; Popovic, Relja; Schutzman, Jennifer; Loboda, Andrey; Chhibber, Aparna; Lehtonen, Heli; McDonough, Stefan; Crohns, Marika; Kulkarni, Diptee; Kaarniranta, Kai; Turunen, Joni A; Ollila, Terhi; Seitsonen, Sanna; Uusitalo, Hannu; Aaltonen, Vesa; Uusitalo-Järvinen, Hannele; Luodonpää, Marja; Hautala, Nina; Loomis, Stephanie; Strauss, Erich; Chen, Hao; Podgornaia, Anna; Hoffman, Joshua; Tasanen, Kaisa; Huilaja, Laura; Hannula-Jouppi, Katariina; Salmi, Teea; Peltonen, Sirkku; Koulu, Leena; Harvima, Ilkka; Wu, Ying; Choy, David; Pussinen, Pirkko; Salminen, Aino; Salo, Tuula; Rice, David; Nieminen, Pekka; Palotie, Ulla; Siponen, Maria; Suominen, Liisa; Mäntylä, Päivi; Gursoy, Ulvi; Anttonen, Vuokko; Sipilä, Kirsi; Davis, Justin Wade; Quarless, Danjuma; Petrovski, Slavé; Wigmore, Eleonor; Chen, Chia-Yen; Bronson, Paola; Tsai, Ellen; Huang, Yunfeng; Maranville, Joseph; Shaikho, Elmutaz; Mohammed, Elhaj; Wadhawan, Samir; Kvikstad, Erika; Caliskan, Minal; Chang, Diana; Bhangale, Tushar; Pendergrass, Sarah; Holzinger, Emily; Chen, Xing; Hedman, Åsa; King, Karen S; Wang, Clarence; Xu, Ethan; Auge, Franck; Chatelain, Clement; Rajpal, Deepak; Liu, Dongyu; Call, Katherine; Xia, Tai-He; Brauer, Matt; Kurki, Mitja; Karjalainen, Juha; Havulinna, Aki; Jalanko, Anu; Palta, Priit; Della Briotta Parolo, Pietro; Zhou, Wei; Lemmelä, Susanna; Rivas, Manuel; Harju, Jarmo; Lehisto, Arto; Ganna, Andrea; Llorens, Vincent; Laivuori, Hannele; Rüeger, Sina; Niemi, Mari E; Tukiainen, Taru; Reeve, Mary Pat; Heyne, Henrike; Palin, Kimmo; Garcia-Tabuenca, Javier; Siirtola, Harri; Kiiskinen, Tuomo; Lee, Jiwoo; Tsuo, Kristin; Elliott, Amanda; Kristiansson, Kati; Hyvärinen, Kati; Ritari, Jarmo; Koskinen, Miika; Pylkäs, Katri; Kalaoja, Marita; Karjalainen, Minna; Mantere, Tuomo; Kangasniemi, Eeva; Heikkinen, Sami; Laakkonen, Eija; Sipeky, Csilla; Heron, Samuel; Karlsson, Antti; Jambulingam, Dhanaprakash; Rathinakannan, Venkat Subramaniam; Kajanne, Risto; Aavikko, Mervi; Jiménez, Manuel González; Della Briotta Parola, Pietro; Lehistö, Arto; Kanai, Masahiro; Kaunisto, Mari; Kilpeläinen, Elina; Sipilä, Timo P; Brein, Georg; Awaisa, Ghazal; Shcherban, Anastasia; Donner, Kati; Loukola, Anu; Laiho, Päivi; Sistonen, Tuuli; Kaiharju, Essi; Laukkanen, Markku; Järvensivu, Elina; Lähteenmäki, Sini; Männikkö, Lotta; Wong, Regis; Mattsson, Hannele; Hiekkalinna, Tero; Paajanen, Teemu; Pärn, Kalle; Gracia-Tabuenca, Javier; Abner, Erin; Adams, Perrie M; Aguirre, Alyssa; Albert, Marilyn S; Albin, Roger L; Allen, Mariet; Alvarez, Lisa; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Ayres, Gayle; Baldwin, Clinton T; Barber, Robert C; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Beecham, Gary W; Beekly, Duane; Below, Jennifer E; Benchek, Penelope; Benitez, Bruno A; Bennett, David; Bertelson, John; Margaret, Flanagan E; Bird, Thomas D; Blacker, Deborah; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Brewer, James; Burke, James R; Burns, Jeffrey M; Bush, Will S; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Christopher S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Chasse, Scott; Chesselet, Marie-Francoise; Chesi, Alessandra; Chin, Nathaniel A; Chui, Helena C; Chung, Jaeyoon; Craft, Suzanne; Crane, Paul K; Cribbs, David H; Crocco, Elizabeth A; Cruchaga, Carlos; Cuccaro, Michael L; Cullum, Munro; Darby, Eveleen; Davis, Barbara; De Jager, Philip L; DeCarli, Charles; DeToledo, John; Dick, Malcolm; Dickson, Dennis W; Dombroski, Beth A; Doody, Rachelle S; Duara, Ranjan; Ertekin-Taner, Nilüfer; Evans, Denis A; Fairchild, Thomas J; Fallon, Kenneth B; Farlow, Martin R; Farrell, John J; Fernandez-Hernandez, Victoria; Ferris, Steven; Frosch, Matthew P; Fulton-Howard, Brian; Galasko, Douglas R; Gamboa, Adriana; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Grabowski, Thomas J; Graff-Radford, Neill R; Grant, Struan F A; Green, Robert C; Growdon, John H; Haines, Jonathan L; Hakonarson, Hakon; Hall, James; Hamilton, Ronald L; Harari, Oscar; Harrell, Lindy E; Haut, Jacob; Head, Elizabeth; Henderson, Victor W; Hernandez, Michelle; Hohman, Timothy; Honig, Lawrence S; Huebinger, Ryan M; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Hynan, Linda S; Ibanez, Laura; Jarvik, Gail P; Jayadev, Suman; Jin, Lee-Way; Johnson, Kim; Johnson, Leigh; Kamboh, M Ilyas; Karydas, Anna M; Katz, Mindy J; Kaye, Jeffrey A; Keene, C Dirk; Khaleeq, Aisha; Kim, Ronald; Knebl, Janice; Kowall, Neil W; Kramer, Joel H; Kuksa, Pavel P; LaFerla, Frank M; Lah, James J; Larson, Eric B; Lee, Chien-Yueh; Lee, Edward B; Lerner, Alan; Leung, Yuk Yee; Leverenz, James B; Levey, Allan I; Li, Mingyao; Lieberman, Andrew P; Lipton, Richard B; Logue, Mark; Lyketsos, Constantine G; Malamon, John; Mains, Douglas; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; Massman, Paul; Masurkar, Arjun; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McDonough, Stefan; McKee, Ann C; Mesulam, Marsel; Mez, Jesse; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Montine, Thomas J; Monuki, Edwin S; Morris, John C; Myers, Amanda J; Nguyen, Trung; O'Bryant, Sid; Olichney, John M; Ory, Marcia; Palmer, Raymond; Parisi, Joseph E; Paulson, Henry L; Pavlik, Valory; Paydarfar, David; Perez, Victoria; Peskind, Elaine; Petersen, Ronald C; Phillips-Cremins, Jennifer E; Pierce, Aimee; Polk, Marsha; Poon, Wayne W; Potter, Huntington; Qu, Liming; Quiceno, Mary; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reiman, Eric M; Reisberg, Barry; Reisch, Joan S; Ringman, John M; Roberson, Erik D; Rodriguear, Monica; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Royall, Donald R; Sager, Mark A; Sano, Mary; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Slifer, Susan H; Small, Scott; Smith, Amanda G; Smith, Janet P; Song, Yeunjoo E; Sonnen, Joshua A; Spina, Salvatore; George-Hyslop, Peter St; Stern, Robert A; Stevens, Alan B; Strittmatter, Stephen M; Sultzer, David; Swerdlow, Russell H; Tanzi, Rudolph E; Tilson, Jeffrey L; Trojanowski, John Q; Troncoso, Juan C; Tsuang, Debby W; Valladares, Otto; Van Deerlin, Vivianna M; van Eldik, Linda J; Vassar, Robert; Vinters, Harry V; Vonsattel, Jean-Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Whitehead, Patrice L; Wijsman, Ellen M; Wilhelmsen, Kirk C; Williams, Benjamin; Williamson, Jennifer; Wilms, Henrik; Wingo, Thomas S; Wisniewski, Thomas; Woltjer, Randall L; Woon, Martin; Wright, Clinton B; Wu, Chuang-Kuo; Younkin, Steven G; Yu, Chang-En; Yu, Lei; Zhang, Yuanchao; Zhao, Yi; Zhu, Xiongwei; Adams, Hieab; Akinyemi, Rufus O; Ali, Muhammad; Armstrong, Nicola; Aparicio, Hugo J; Bahadori, Maryam; Becker, James T; Breteler, Monique; Chasman, Daniel; Chauhan, Ganesh; Comic, Hata; Cox, Simon; Cupples, Adrienne L; Davies, Gail; DeCarli, Charles S; Duperron, Marie-Gabrielle; Dupuis, Josée; Evans, Tavia; Fan, Frank; Fitzpatrick, Annette; Fohner, Alison E; Ganguli, Mary; Geerlings, Mirjam; Glatt, Stephen J; Gonzalez, Hector M; Goss, Monica; Grabe, Hans; Habes, Mohamad; Heckbert, Susan R; Hofer, Edith; Hong, Elliot; Hughes, Timothy; Kautz, Tiffany F; Knol, Maria; Kremen, William; Lacaze, Paul; Lahti, Jari; Grand, Quentin Le; Litkowski, Elizabeth; Li, Shuo; Liu, Dan; Liu, Xuan; Loitfelder, Marisa; Manning, Alisa; Maillard, Pauline; Marioni, Riccardo; Mazoyer, Bernard; van Lent, Debora Melo; Mei, Hao; Mishra, Aniket; Nyquist, Paul; O'Connell, Jeffrey; Patel, Yash; Paus, Tomas; Pausova, Zdenka; Raikkonen-Talvitie, Katri; Riaz, Moeen; Rich, Stephen; Rotter, Jerome; Romero, Jose; Roshchupkin, Gena; Saba, Yasaman; Sargurupremraj, Murali; Schmidt, Helena; Schmidt, Reinhold; Shulman, Joshua M; Smith, Jennifer; Sekhar, Hema; Rajula, Reddy; Shin, Jean; Simino, Jeannette; Sliz, Eeva; Teumer, Alexander; Thomas, Alvin; Tin, Adrienne; Tucker-Drob, Elliot; Vojinovic, Dina; Wang, Yanbing; Weinstein, Galit; Williams, Dylan; Wittfeld, Katharina; Yanek, Lisa; Yang, Yunju
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092

Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms

Rosen, Rebecca; Shao, Yongzhao; Zhang, Qiao; Bao, Jia; Zhang, Yian; Masurkar, Arjun; Wisniewski, Thomas; Urban, Nina; Reibman, Joan
The World Trade Center Environmental Health Center (WTC EHC), is a federally designated clinical center of excellence for surveillance and treatment of WTC disaster exposed community members (WTC Survivors). Cognitive impairment (CI) has been extensively described in WTC responders and a concern for progressive impairment in all WTC disaster exposed groups has been raised. Cognitive status, however, has not been systematically characterized in the WTC Survivor population. We describe cognitive status in a subgroup of the Survivor population referred for mental health evaluation (N = 480) in the WTC EHC as measured by scores on the Montreal Cognitive Assessment (MoCA) instrument, and examine their association with WTC exposures and individual-level covariates including PTSD and depression screening inventory scores. In regression analyses, probable cognitive impairment (MoCA score < 26) was found in 59% of the study subjects and was significantly associated with age, race/ethnicity, education, income, depression and PTSD scores. Being caught in the dust cloud on 11 September 2011 was significantly associated with cognitive impairment even after controlling for the above. These data suggest an association with cognitive dysfunction in WTC Survivors with exposure to the toxic dust/fumes and psychological stress from the 9/11 terrorist attack and warrant further systematic study.
PMCID:8948727
PMID: 35329128
ISSN: 1660-4601
CID: 5184832

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection

Wu, Shirley Z; Nolan-Kenney, Rachel; Moehringer, Nicholas J; Hasanaj, Lisena F; Joseph, Binu M; Clayton, Ashley M; Rucker, Janet C; Galetta, Steven L; Wisniewski, Thomas M; Masurkar, Arjun V; Balcer, Laura J
BACKGROUND:Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study. METHODS:Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data. RESULTS:Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores. CONCLUSIONS:Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.
PMID: 34029274
ISSN: 1536-5166
CID: 4878882

Medication utilization among vascular dementia population

Razavian, Narges; Dodson, John; Masurkar, Arjun V; Wisniewski, Thomas; Horwitz, Leora; Aphinyanaphongs, Yindalon
BACKGROUND:It is estimated that up to 40% of Alzheimer's Disease and Related Dementias cases can be prevented or delayed by addressing modifiable factors including those that influence vascular risk (hypertension, obesity, smoking, physical activity, diabetes). Prevention may be particularly important in the vascular dementia subtypes. Despite the supporting evidence, the rates of medical therapy to reduce vascular risk are not well described. METHOD/METHODS:We assessed the utilization of statins, aspirin, and blood pressure (BP) medications in adults age ≥65 years cared for at NYU Langone Health, as recorded in the electronic health record. We included two cohorts: cohort 1 included patients who were diagnosed with vascular dementia (VaD) at NYU Langone Barlow Center for Memory Evaluation between January 1, 2015 and June 24, 2019. Cohort 2 extended the inclusion to seniors with VD diagnosis by any NYU Langone physician. Definitions for vascular dementia, the covariates assessed, and medications that we included in each category are shown in Tables 1-3. RESULT/RESULTS:We included 419 and 3745 patients in cohort 1 and cohort 2, respectively. Table 4 shows the characteristics and medication adherence in cohorts 1 and 2. In cohort 1, the prescription rates for statins, aspirin, and BP medications were 66%, 66%, 70%. In cohort 2, the rates for statin, aspirin, and BP medications were 56%, 46%, and 65%, respectively. The differences between prescription rates in cohort 1 and 2 for the three medication groups were statistically significant (p<0.05). CONCLUSION/CONCLUSIONS:Our analysis of the utilization of cardiovascular medications among patients with vascular dementia illuminates potential gaps both among patients who receive care at specialty clinics, as well as the overall population with vascular dementia. The rates of medication utilization are higher for patients under the care of cognitive neurologists. Electronic health records can help identify large cohorts of patients who may benefit from improved access to preventative measures including cardiovascular medications.
PMID: 34971267
ISSN: 1552-5279
CID: 5108332

Journal Club: Diffusion-weighted MRI in Transient Global Amnesia and its Diagnostic Implications [Editorial]

Talmasov, Daniel; Masurkar, Arjun V
PMID: 33310875
ISSN: 1526-632x
CID: 4712542

Clinical Profiles of Arteriolosclerosis and Alzheimer Disease at Mild Cognitive Impairment and Mild Dementia in a National Neuropathology Cohort

Yang, Dixon; Masurkar, Arjun V
OBJECTIVE:We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE). METHODS:Using National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively. RESULTS:In MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE. CONCLUSIONS:Differences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.
PMID: 32925200
ISSN: 1546-4156
CID: 4650242

Development of a Deep Learning Model for Early Alzheimer’s Disease Detection from Structural MRIs and External Validation on an Independent Cohort

Liu, Sheng; Masurkar, Arjun V; Rusinek, Henry; Chen, Jingyun; Zhang, Ben; Zhu, Weicheng; Fernandez-Granda, Carlos; Razavian, Narges
ORIGINAL:0015178
ISSN: n/a
CID: 4903432

The Relationship of Anxiety with Alzheimer's Disease: A Narrative Review

Patel, Palak; Masurkar, Arjun V
BACKGROUND:There is an increased effort to better understand neuropsychiatric symptoms of Alzheimer's disease (AD) as an important feature of symptomatic burden as well as potential modi- fiable factors of the disease process. Anxiety is one of the most common neuropsychiatric symptoms in Alzheimer's disease (AD). A growing body of work has emerged that addresses the epidemiology and biological correlations of anxiety in AD. OBJECTIVE AND METHODS/OBJECTIVE:Here, we review human studies in research and clinical cohorts that examined anxiety in AD. We focused on work related to prevalence across AD stages, correlation with established biomarkers, relationship with AD neuropathology and genetic risk factors, and impact on progression. RESULTS:Anxiety is prominent in the early stages and increases across the spectrum of functional stages. Biomarker relationships are strongest at the level of FDG-PET and amyloid measured via PET or cerebrospinal fluid analysis. Neuropathologically, anxiety emerges with early Braak stage tau pathology. The presence of the apolipoprotein E e4 allele is associated with increased anxiety at all stages, most notably at mild cognitive impairment. Anxiety portended a faster progression at all pre-dementia stages. CONCLUSION/CONCLUSIONS:This body of work suggests a close biological relationship between anxiety and AD that begins in early stages and influences functional decline. As such, we discuss future work that would improve our understanding of this relationship and test the validity of anxiolytic treatment as disease modifying therapy for AD.
PMID: 34429045
ISSN: 1875-5828
CID: 4980082