Searched for: person:reisbb01
Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Kunkle, Brian W; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C; Damotte, Vincent; Naj, Adam C; Boland, Anne; Vronskaya, Maria; van der Lee, Sven J; Amlie-Wolf, Alexandre; Bellenguez, Céline; Frizatti, Aura; Chouraki, Vincent; Martin, Eden R; Sleegers, Kristel; Badarinarayan, Nandini; Jakobsdottir, Johanna; Hamilton-Nelson, Kara L; Moreno-Grau, Sonia; Olaso, Robert; Raybould, Rachel; Chen, Yuning; Kuzma, Amanda B; Hiltunen, Mikko; Morgan, Taniesha; Ahmad, Shahzad; Vardarajan, Badri N; Epelbaum, Jacques; Hoffmann, Per; Boada, Merce; Beecham, Gary W; Garnier, Jean-Guillaume; Harold, Denise; Fitzpatrick, Annette L; Valladares, Otto; Moutet, Marie-Laure; Gerrish, Amy; Smith, Albert V; Qu, Liming; Bacq, Delphine; Denning, Nicola; Jian, Xueqiu; Zhao, Yi; Del Zompo, Maria; Fox, Nick C; Choi, Seung-Hoan; Mateo, Ignacio; Hughes, Joseph T; Adams, Hieab H; Malamon, John; Sanchez-Garcia, Florentino; Patel, Yogen; Brody, Jennifer A; Dombroski, Beth A; Naranjo, Maria Candida Deniz; Daniilidou, Makrina; Eiriksdottir, Gudny; Mukherjee, Shubhabrata; Wallon, David; Uphill, James; Aspelund, Thor; Cantwell, Laura B; Garzia, Fabienne; Galimberti, Daniela; Hofer, Edith; Butkiewicz, Mariusz; Fin, Bertrand; Scarpini, Elio; Sarnowski, Chloe; Bush, Will S; Meslage, Stéphane; Kornhuber, Johannes; White, Charles C; Song, Yuenjoo; Barber, Robert C; Engelborghs, Sebastiaan; Sordon, Sabrina; Voijnovic, Dina; Adams, Perrie M; Vandenberghe, Rik; Mayhaus, Manuel; Cupples, L Adrienne; Albert, Marilyn S; De Deyn, Peter P; Gu, Wei; Himali, Jayanadra J; Beekly, Duane; Squassina, Alessio; Hartmann, Annette M; Orellana, Adelina; Blacker, Deborah; Rodriguez-Rodriguez, Eloy; Lovestone, Simon; Garcia, Melissa E; Doody, Rachelle S; Munoz-Fernadez, Carmen; Sussams, Rebecca; Lin, Honghuang; Fairchild, Thomas J; Benito, Yolanda A; Holmes, Clive; Karamujić-ÄŒomić, Hata; Frosch, Matthew P; Thonberg, Hakan; Maier, Wolfgang; Roschupkin, Gena; Ghetti, Bernardino; Giedraitis, Vilmantas; Kawalia, Amit; Li, Shuo; Huebinger, Ryan M; Kilander, Lena; Moebus, Susanne; Hernández, Isabel; Kamboh, M Ilyas; Brundin, RoseMarie; Turton, James; Yang, Qiong; Katz, Mindy J; Concari, Letizia; Lord, Jenny; Beiser, Alexa S; Keene, C Dirk; Helisalmi, Seppo; Kloszewska, Iwona; Kukull, Walter A; Koivisto, Anne Maria; Lynch, Aoibhinn; Tarraga, LluÃs; Larson, Eric B; Haapasalo, Annakaisa; Lawlor, Brian; Mosley, Thomas H; Lipton, Richard B; Solfrizzi, Vincenzo; Gill, Michael; Longstreth, W T; Montine, Thomas J; Frisardi, Vincenza; Diez-Fairen, Monica; Rivadeneira, Fernando; Petersen, Ronald C; Deramecourt, Vincent; Alvarez, Ignacio; Salani, Francesca; Ciaramella, Antonio; Boerwinkle, Eric; Reiman, Eric M; Fievet, Nathalie; Rotter, Jerome I; Reisch, Joan S; Hanon, Olivier; Cupidi, Chiara; Andre Uitterlinden, A G; Royall, Donald R; Dufouil, Carole; Maletta, Raffaele Giovanni; de Rojas, Itziar; Sano, Mary; Brice, Alexis; Cecchetti, Roberta; George-Hyslop, Peter St; Ritchie, Karen; Tsolaki, Magda; Tsuang, Debby W; Dubois, Bruno; Craig, David; Wu, Chuang-Kuo; Soininen, Hilkka; Avramidou, Despoina; Albin, Roger L; Fratiglioni, Laura; Germanou, Antonia; Apostolova, Liana G; Keller, Lina; Koutroumani, Maria; Arnold, Steven E; Panza, Francesco; Gkatzima, Olymbia; Asthana, Sanjay; Hannequin, Didier; Whitehead, Patrice; Atwood, Craig S; Caffarra, Paolo; Hampel, Harald; Quintela, Inés; Carracedo, Ãngel; Lannfelt, Lars; Rubinsztein, David C; Barnes, Lisa L; Pasquier, Florence; Frölich, Lutz; Barral, Sandra; McGuinness, Bernadette; Beach, Thomas G; Johnston, Janet A; Becker, James T; Passmore, Peter; Bigio, Eileen H; Schott, Jonathan M; Bird, Thomas D; Warren, Jason D; Boeve, Bradley F; Lupton, Michelle K; Bowen, James D; Proitsi, Petra; Boxer, Adam; Powell, John F; Burke, James R; Kauwe, John S K; Burns, Jeffrey M; Mancuso, Michelangelo; Buxbaum, Joseph D; Bonuccelli, Ubaldo; Cairns, Nigel J; McQuillin, Andrew; Cao, Chuanhai; Livingston, Gill; Carlson, Chris S; Bass, Nicholas J; Carlsson, Cynthia M; Hardy, John; Carney, Regina M; Bras, Jose; Carrasquillo, Minerva M; Guerreiro, Rita; Allen, Mariet; Chui, Helena C; Fisher, Elizabeth; Masullo, Carlo; Crocco, Elizabeth A; DeCarli, Charles; Bisceglio, Gina; Dick, Malcolm; Ma, Li; Duara, Ranjan; Graff-Radford, Neill R; Evans, Denis A; Hodges, Angela; Faber, Kelley M; Scherer, Martin; Fallon, Kenneth B; Riemenschneider, Matthias; Fardo, David W; Heun, Reinhard; Farlow, Martin R; Kölsch, Heike; Ferris, Steven; Leber, Markus; Foroud, Tatiana M; Heuser, Isabella; Galasko, Douglas R; Giegling, Ina; Gearing, Marla; Hüll, Michael; Geschwind, Daniel H; Gilbert, John R; Morris, John; Green, Robert C; Mayo, Kevin; Growdon, John H; Feulner, Thomas; Hamilton, Ronald L; Harrell, Lindy E; Drichel, Dmitriy; Honig, Lawrence S; Cushion, Thomas D; Huentelman, Matthew J; Hollingworth, Paul; Hulette, Christine M; Hyman, Bradley T; Marshall, Rachel; Jarvik, Gail P; Meggy, Alun; Abner, Erin; Menzies, Georgina E; Jin, Lee-Way; Leonenko, Ganna; Real, Luis M; Jun, Gyungah R; Baldwin, Clinton T; Grozeva, Detelina; Karydas, Anna; Russo, Giancarlo; Kaye, Jeffrey A; Kim, Ronald; Jessen, Frank; Kowall, Neil W; Vellas, Bruno; Kramer, Joel H; Vardy, Emma; LaFerla, Frank M; Jöckel, Karl-Heinz; Lah, James J; Dichgans, Martin; Leverenz, James B; Mann, David; Levey, Allan I; Pickering-Brown, Stuart; Lieberman, Andrew P; Klopp, Norman; Lunetta, Kathryn L; Wichmann, H-Erich; Lyketsos, Constantine G; Morgan, Kevin; Marson, Daniel C; Brown, Kristelle; Martiniuk, Frank; Medway, Christopher; Mash, Deborah C; Nöthen, Markus M; Masliah, Eliezer; Hooper, Nigel M; McCormick, Wayne C; Daniele, Antonio; McCurry, Susan M; Bayer, Anthony; McDavid, Andrew N; Gallacher, John; McKee, Ann C; van den Bussche, Hendrik; Mesulam, Marsel; Brayne, Carol; Miller, Bruce L; Riedel-Heller, Steffi; Miller, Carol A; Miller, Joshua W; Al-Chalabi, Ammar; Morris, John C; Shaw, Christopher E; Myers, Amanda J; Wiltfang, Jens; O'Bryant, Sid; Olichney, John M; Alvarez, Victoria; Parisi, Joseph E; Singleton, Andrew B; Paulson, Henry L; Collinge, John; Perry, William R; Mead, Simon; Peskind, Elaine; Cribbs, David H; Rossor, Martin; Pierce, Aimee; Ryan, Natalie S; Poon, Wayne W; Nacmias, Benedetta; Potter, Huntington; Sorbi, Sandro; Quinn, Joseph F; Sacchinelli, Eleonora; Raj, Ashok; Spalletta, Gianfranco; Raskind, Murray; Caltagirone, Carlo; Bossù, Paola; Orfei, Maria Donata; Reisberg, Barry; Clarke, Robert; Reitz, Christiane; Smith, A David; Ringman, John M; Warden, Donald; Roberson, Erik D; Wilcock, Gordon; Rogaeva, Ekaterina; Bruni, Amalia Cecilia; Rosen, Howard J; Gallo, Maura; Rosenberg, Roger N; Ben-Shlomo, Yoav; Sager, Mark A; Mecocci, Patrizia; Saykin, Andrew J; Pastor, Pau; Cuccaro, Michael L; Vance, Jeffery M; Schneider, Julie A; Schneider, Lori S; Slifer, Susan; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tang, Mitchell; Tanzi, Rudolph E; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Saba, Yasaman; Pilotto, Alberto; Bullido, Maria J; Peters, Oliver; Crane, Paul K; Bennett, David; Bosco, Paola; Coto, Eliecer; Boccardi, Virginia; De Jager, Phil L; Lleo, Alberto; Warner, Nick; Lopez, Oscar L; Ingelsson, Martin; Deloukas, Panagiotis; Cruchaga, Carlos; Graff, Caroline; Gwilliam, Rhian; Fornage, Myriam; Goate, Alison M; Sanchez-Juan, Pascual; Kehoe, Patrick G; Amin, Najaf; Ertekin-Taner, Nilifur; Berr, Claudine; Debette, Stéphanie; Love, Seth; Launer, Lenore J; Younkin, Steven G; Dartigues, Jean-Francois; Corcoran, Chris; Ikram, M Arfan; Dickson, Dennis W; Nicolas, Gael; Campion, Dominique; Tschanz, JoAnn; Schmidt, Helena; Hakonarson, Hakon; Clarimon, Jordi; Munger, Ron; Schmidt, Reinhold; Farrer, Lindsay A; Van Broeckhoven, Christine; C O'Donovan, Michael; DeStefano, Anita L; Jones, Lesley; Haines, Jonathan L; Deleuze, Jean-Francois; Owen, Michael J; Gudnason, Vilmundur; Mayeux, Richard; Escott-Price, Valentina; Psaty, Bruce M; Ramirez, Alfredo; Wang, Li-San; Ruiz, Agustin; van Duijn, Cornelia M; Holmans, Peter A; Seshadri, Sudha; Williams, Julie; Amouyel, Phillippe; Schellenberg, Gerard D; Lambert, Jean-Charles; Pericak-Vance, Margaret A
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
PMID: 30820047
ISSN: 1546-1718
CID: 3699012
Two Year Outcomes, Cognitive and Behavioral Markers of Decline in Healthy, Cognitively Normal Older Persons with Global Deterioration Scale Stage 2 (Subjective Cognitive Decline with Impairment)
Reisberg, Barry; Torossian, Carol; Shulman, Melanie B; Monteiro, Isabel; Boksay, Istvan; Golomb, James; Guillo Benarous, Francoise; Ulysse, Anaztasia; Oo, Thet; Vedvyas, Alok; Rao, Julia A; Marsh, Karyn; Kluger, Alan; Sangha, Jaspreet; Hassan, Mudasar; Alshalabi, Munther; Arain, Fauzia; Shaikh, Naveed; Buj, Maja; Kenowsky, Sunnie; Masurkar, Arjun V; Rabin, Laura; Noroozian, Maryam; Sánchez-Saudinós, Mar A Belén; Blesa, Rafael; Auer, Stefanie; Zhang, Yian; de Leon, Mony; Sadowski, Martin; Wisniewski, Thomas; Gauthier, Serge; Shao, Yongzhao
BACKGROUND:Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. OBJECTIVE:Two-year interval behavioral markers were investigated herein. METHODS:Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12±8.75 years, with a mean educational background of 15.55±2.60 years, and mean baseline MMSE scores of 28.9±1.24 were followed for 2.13±0.30 years. RESULTS:Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (p < 0.001), with component declines in Remote memory (p < 0.01), and Functioning/self-care (p = 0.01). CONCLUSION/CONCLUSIONS:SCD(I) persons decline at an annual rate of approximately 6.7% /year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.
PMID: 30689585
ISSN: 1875-8908
CID: 3626022
CpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease
Ma, Yiyi; Jun, Gyungah R.; Chung, Jaeyoon; Zhang, Xiaoling; Kunkle, Brian W.; Naj, Adam C.; White, Charles C.; Bennett, David A.; De Jager, Philip L.; Mayeux, Richard; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Farrer, Lindsay A.; Lunetta, Kathryn L.; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Asthana, Sanjay; Atwood, Craig S.; Baldwin, Clinton T.; Barmada, Michael M.; Barnes, Lisa L.; Beach, Thomas G.; Becker, James T.; Beekly, Duane; Benonett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boeve, Bradley F.; Bowen, James D.; Boxer, Adam; Burke, James R.; Buxbaum, Joseph; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carlson, Chris S.; Carlsson, Cynthia M.; Carney, Regina M.; Carrasquillo, Minerva M.; Carroll, Steven L.; Chui, Helena C.; Clark; Crane, Paul; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; De Jager, Philip; Dick, Malcolm; Dickson, Dennis; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew; Galasko, Douglas R.; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton, Ronald L.; Hamilton-Nelson, Kara L.; Hardy, John; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Huentelman, Matthew J.; Hulette, Christine M.; Hyman, Bradley; Jarvik, Gail P.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kauwe, John S. K.; Kaye, Jeffrey A.; Kim, Ronald; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter; Kunkle, Brian W.; LaFerla, Frank M.; Lah, James J.; Larson, Eric; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lieberman, Andrew P.; Lin, Chiao-Feng; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah; Masliah, Eliezer; McCormick, Wayne C.; McCurry, Susan M.; McDavid, Andrew N.; Mckee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Morris, John C.; Mukherjee, Shubhabrata; Murrell, Jill R.; Myers, Amanda J.; Naj, Adam C.; Olichney, John M.; Pankratz, Vernon S.; Parisi, Joseph E.; Partch, Amanda; Paulson, Henry L.; Perry, William; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rogaeva, Ekaterina; Rosen, Howard J.; Rosenberg, Roger N.; Sager, Mark A.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Hyslop, Peter St George; Stern, Robert A.; Tanzi, Rudolph E.; Thornton-Wells, Tricia A.; Trojanowski, John; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean-Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Wishnek, Sarah; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven; Yu, Chang-En; Yu, Lei
ISI:000476767500015
ISSN: 1474-9718
CID: 4028452
Subjective memory complaints predict baseline but not future cognitive function over three years: results from the Western Australia Memory Study
Sohrabi, Hamid R; Weinborn, Michael; Laske, Christoph; Bates, Kristyn A; Christensen, Daniel; Taddei, Kevin; Rainey-Smith, Stephanie R; Brown, Belinda M; Gardener, Samantha L; Laws, Simon M; Martins, Georgia; Burnham, Samantha C; Bucks, Romola S; Reisberg, Barry; Lautenschlager, Nicola T; Foster, Jonathan; Martins, Ralph N
ABSTRACTBackground:This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions.
PMID: 30277188
ISSN: 1741-203x
CID: 3327862
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Celine; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nothen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cecile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Celine; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sanchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josee; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-Garcia, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henandez, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Jr, W T Longstreth; Fairchild, Thomas J; Bossu, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairen, Monica Diez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleo, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Munoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stahlbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, Maria J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimon, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-Francois; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-Francois; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 x 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 x 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 x 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 x 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 x 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
PMCID:5669039
PMID: 28714976
ISSN: 1546-1718
CID: 2640222
Multiregional Age-Associated Reduction of Brain Neuronal Reserve Without Association With Neurofibrillary Degeneration or beta-Amyloidosis
Wegiel, Jerzy; Flory, Michael; Kuchna, Izabela; Nowicki, Krzysztof; Yong Ma, Shuang; Wegiel, Jarek; Badmaev, Eulalia; Silverman, Wayne P; de Leon, Mony; Reisberg, Barry; Wisniewski, Thomas
Increase in human life expectancy has resulted in the rapid growth of the elderly population with minimal or no intellectual deterioration. The aim of this stereological study of 10 structures and 5 subdivisions with and without neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was to establish the pattern of age-associated neurodegeneration and neuronal loss in the brains of nondemented adults and elderly. The study revealed the absence of significant neuronal loss in 7 regions and topographically selective reduction of neuronal reserve over 77 years in 8 brain structures including the entorhinal cortex (EC) (-33.3%), the second layer of the EC (-54%), cornu Ammonis sector 1 (CA1) (-28.5%), amygdala, (-45.8%), thalamus (-40.5%), caudate nucleus (-35%), Purkinje cells (-48.3%), and neurons in the dentate nucleus (40.1%). A similar rate of neuronal loss in adults and elderly, without signs of accelerating neuronal loss in agers or super-agers, appears to indicate age-associated brain remodeling with significant reduction of neuronal reserve in 8 brain regions. Multivariate analysis demonstrates the absence of a significant association between neuronal loss and the severity of neurofibrillary degeneration and beta-amyloidosis, and a similar rate of age-associated neuronal loss in structures with and without neurofibrillary degeneration.
PMCID:5901097
PMID: 28505333
ISSN: 1554-6578
CID: 2562682
Implementation of subjective cognitive decline criteria in research studies
Molinuevo, Jose L; Rabin, Laura A; Amariglio, Rebecca; Buckley, Rachel; Dubois, Bruno; Ellis, Kathryn A; Ewers, Michael; Hampel, Harald; Kloppel, Stefan; Rami, Lorena; Reisberg, Barry; Saykin, Andrew J; Sikkes, Sietske; Smart, Colette M; Snitz, Beth E; Sperling, Reisa; van der Flier, Wiesje M; Wagner, Michael; Jessen, Frank
INTRODUCTION: Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. METHODS: Members of the SCD-I met to identify and agree on topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. RESULTS: Topics included SCD inclusion and exclusion criteria, together with the informant's role in defining SCD presence and the impact of demographic factors. DISCUSSION: Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies.
PMCID:5344703
PMID: 27825022
ISSN: 1552-5279
CID: 2304372
Comprehensive, Individualized, Person-Centered Management of Community-Residing Persons with Moderate-to-Severe Alzheimer Disease: A Randomized Controlled Trial
Reisberg, Barry; Shao, Yongzhao; Golomb, James; Monteiro, Isabel; Torossian, Carol; Boksay, Istvan; Shulman, Melanie; Heller, Sloane; Zhu, Zhaoyin; Atif, Ayesha; Sidhu, Jaskirat; Vedvyas, Alok; Kenowsky, Sunnie
BACKGROUND/AIMS: The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment. METHODS: This was a 28-week, clinician-blinded, randomized, controlled, parallel-group study, with a similar study population, similar eligibility criteria, and a similar design to the memantine pivotal trial of Reisberg et al. [N Engl J Med 2003;348:1333-1341]. Twenty eligible community-residing Alzheimer disease (AD) subject-caregiver dyads were randomized to the CI-PCM program (n = 10) or to usual community care (n = 10). Primary outcomes were the New York University Clinician's Interview-Based Impression of Change Plus Caregiver Input (NYU-CIBIC-Plus), assessed by one clinician set, and an activities of daily living inventory, assessed by a separate clinician set at baseline and at weeks 4, 12, and 28. RESULTS: Primary outcomes showed significant benefits of the CI-PCM program at all post-baseline evaluations. Improvement on the NYU-CIBIC-Plus in the management group at 28 weeks was 2.9 points over the comparator group. The memantine 2003 trial showed an improvement of 0.3 points on this global measure in memantine-treated versus placebo-randomized subjects at 28 weeks. Hence, globally, the management program intervention benefits were 967% greater than memantine treatment alone. CONCLUSION: These results are approximately 10 times those usually observed with both nonpharmacological and pharmacological treatments and indicate substantial benefits with the management program for advanced AD persons.
PMCID:5562438
PMID: 28122366
ISSN: 1421-9824
CID: 2418532
Alzheimer's disease
Chapter by: Reisberg, Barry; Franssen, Emile; Souren, Liduin EM; Kenowsky, Sunnie; Janjua, Khurram S; Veigne, Sandra W; Guillo-Benarous, Francoise; Singh, Satneet; Khizar, Asma; Shah, Umang; Shah, Romi G; Bhandal, Amandeep; Auer, Stefanie
in: Medical aspects of disability for the rehabilitation professionals by Moroz, Alex; Flanagan, Steven R; Zaretsky, Herbert H [Eds]
[New York] : Springer Publishing Company, 2017
pp. ?-?
ISBN: 9780826133199
CID: 2558782
Ecopsychosocial Interventions in Cognitive Decline and Dementia: A New Terminology and a New Paradigm
Zeisel, John; Reisberg, Barry; Whitehouse, Peter; Woods, Robert; Verheul, Ad
Dementia is a major medical and social scourge. Neither pharmacological nor nonpharmacological interventions and treatments have received sufficient funding to be meaningful in combatting this tsunami. Because the term-"nonpharmacological"-refers to what these interventions are not, rather than what they are, nonpharmacological treatments face a special set of challenges to be recognized, accepted, funded, and implemented. In some ways, the current situation is analogous to using the term "nonhate" to mean "love." This article presents a carefully reasoned argument for using the terminology "ecopsychosocial" to describe the full range of approaches and interventions that fall into this category. These include interventions such as educational efforts with care partners, social support programs for individuals with various levels of dementia, efforts to improve community awareness of dementia, an intergenerational school where persons with dementia teach young children, and the design of residential and community settings that improve functioning and can reduce behavioral symptoms of dementia. The proposed terminology relates to the nature of the interventions themselves, rather than their outcomes, and reflects the broadest range of interventions possible under the present rubric-nonpharmacological. The goal of this new label is to be better able to compare interventions and their outcomes and to be able to see the connections between data sets presently not seen as fitting together, thereby encouraging greater focus on developing new ecopsychosocial interventions and approaches that can improve the lives of those with dementia, their care partners, and the broader society.
PMID: 27284206
ISSN: 1938-2731
CID: 2136602
