Browsing by Author "DeCarli, Charles"

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    Amyloid PET predicts longitudinal functional and cognitive trajectories in a heterogeneous cohort
    (Wiley, 2025) Younes, Kyan; Johns, Emily; Young, Christina B.; Kennedy, Gabriel; Mukherjee, Shubhabrata; Vossler, Hillary A.; Winer, Joseph; Cody, Karly; Henderson, Victor W.; Poston, Kathleen L.; Betthauser, Tobey J.; Bevis, Bill; Brooks, William M.; Burns, Jeffrey M.; Coombes, Stephen A.; DeCarli, Charles; DiFilippo, Frank P.; Duara, Ranjan; Fan, Audrey P.; Gibbons, Laura E.; Golde, Todd; Johnson, Sterling C.; Lepping, Rebecca J.; Leverenz, James; McDougall, Sean; Rogalski, Emily; Sanders, Elizabeth; Pasaye, Joshua; Sridhar, Jaiashre; Saykin, Andrew J.; Sridharan, Anjali; Swerdlow, Russell; Trittschuh, Emily H.; Vaillancourt, David; Vidoni, Eric; Wang, Wei-En; Mez, Jesse; Hohman, Timothy J.; Tosun, Duygu; Biber, Sarah; Kukull, Walter A.; Crane, Paul K.; Mormino, Elizabeth C.; Radiology and Imaging Sciences, School of Medicine
    Introduction: Amyloid positron emission tomography (PET) is increasingly available for diagnosis of Alzheimer`s disease (AD); however, its practical implications in heterogenous cohorts are debated. Methods: Amyloid PET from 890 National Alzheimer`s Coordinating Center participants with up to 10 years post-PET follow up was analyzed. Cox proportional hazards and linear mixed models were used to investigate amyloid burden prediction of etiology and prospective functional status and cognitive decline. Results: Amyloid positivity was associated with progression from unimpaired to mild cognitive impairment and dementia. Amyloid burden in the unimpaired group was associated with lower initial memory levels and faster decline in memory, language, and global cognition. In the Impaired group, amyloid was associated with lower initial levels and faster decline for memory, language, executive function, and global cognition. Discussion: Amyloid burden is an important prognostic marker in a clinically heterogeneous cohort. Future work is needed to establish the proportion of decline driven by AD versus non-AD processes in the context of mixed pathology. Highlights: Our findings highlight the importance of amyloid positron emission tomography (PET) in heterogenous cohorts, including diverse demographics, clinical syndromes, and underlying etiologies. The results also provide evidence that higher amyloid levels were linked to functional progression from unimpaired cognition to mild cognitive impairment (MCI) and from MCI to dementia. In cognitively unimpaired individuals, higher amyloid burden was associated with poorer memory at baseline and subsequent declines in memory, language, and global cognition. Among individuals with cognitive impairment, amyloid burden was associated with worse initial memory, language, executive function, and global cognition, and faster declines over time.
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    Development and validation of a harmonized memory score for multicenter Alzheimer's disease and related dementia research
    (medRxiv, 2025-04-03) Sanderson-Cimino, Mark; Gross, Alden L.; Gaynor, Leslie S.; Paolillo, Emily W.; Saloner, Rowan; Albert, Marilyn S.; Apostolova, Liana G.; Boersema, Brooke; Boxer, Adam L.; Boeve, Bradley F.; Casaletto, Kaitlin B.; Hallgarth, Savannah R.; Diaz, Valentina E.; Clark, Lindsay R.; Maillard, Pauline; Eloyan, Ani; Tomaszewski Farias, Sarah; Gonzales, Mitzi M.; Hammers, Dustin B.; La Joie, Renaud; Cobigo, Yann; Wolf, Amy; Hampstead, Benjamin M.; Mechanic-Hamilton, Dawn; Miller, Bruce L.; Rabinovici, Gil D.; Ringman, John M.; Rosen, Howie J.; Ryman, Sephira G.; Prestopnik, Jillian L.; Salmon, David P.; Smith, Glenn E.; DeCarli, Charles; Rajan, Kumar B.; Jin, Lee-Way; Hinman, Jason; Johnson, David K.; Harvey, Danielle; Fornage, Myriam; Kramer, Joel H.; Staffaroni, Adam M.; Neurology, School of Medicine
    Introduction: List-learning tasks are important for characterizing memory in ADRD research, but the Uniform Data Set neuropsychological battery (UDS-NB) lacks a list-learning paradigm; thus, sites administer a range of tests. We developed a harmonized memory composite that incorporates UDS memory tests and multiple list-learning tasks. Methods: Item-banking confirmatory factor analysis was applied to develop a memory composite in a diagnostically heterogenous sample (n=5943) who completed the UDS-NB and one of five list-learning tasks. Construct validity was evaluated through associations with demographics, disease severity, cognitive tasks, brain volume, and plasma phosphorylated tau (p-tau181 and p-tau217). Test-retest reliability was assessed. Analyses were replicated in a racially/ethnically diverse cohort (n=1058). Results: Fit indices, loadings, distributions, and test-retest reliability were adequate. Expected associations with demographics and clinical measures within development and validation cohorts supported validity. Discussion: This composite enables researchers to incorporate multiple list-learning tasks with other UDS measures to create a single metric.
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    Genetic architecture of subcortical brain structures in 38,851 individuals
    (Nature, 2019-11) Satizabal, Claudia L.; Adams, Hieab H. H.; Hibar, Derrek P.; White, Charles C.; Knol, Maria J.; Stein, Jason L.; Scholz, Markus; Sargurupremraj, Muralidharan; Jahanshad, Neda; Roshchupkin, Gennady V.; Smith, Albert V.; Bis, Joshua C.; Jian, Xueqiu; Luciano, Michelle; Hofer, Edith; Teumer, Alexander; van der Lee, Sven J.; Yang, Jingyun; Yanek, Lisa R.; Lee, Tom V.; Li, Shuo; Hu, Yanhui; Koh, Jia Yu; Eicher, John D.; Desrivières, Sylvane; Arias-Vasquez, Alejandro; Chauhan, Ganesh; Athanasiu, Lavinia; Rentería, Miguel E.; Kim, Sungeun; Hoehn, David; Armstrong, Nicola J.; Chen, Qiang; Holmes, Avram J.; den Braber, Anouk; Kloszewska, Iwona; Andersson, Micael; Espeseth, Thomas; Grimm, Oliver; Abramovic, Lucija; Alhusaini, Saud; Milaneschi, Yuri; Papmeyer, Martina; Axelsson, Tomas; Ehrlich, Stefan; Roiz-Santiañez, Roberto; Kraemer, Bernd; Håberg, Asta K.; Jones, Hannah J.; Pike, G. Bruce; Stein, Dan J.; Stevens, Allison; Bralten, Janita; Vernooij, Meike W.; Harris, Tamara B.; Filippi, Irina; Witte, A. Veronica; Guadalupe, Tulio; Wittfeld, Katharina; Mosley, Thomas H.; Becker, James T.; Doan, Nhat Trung; Hagenaars, Saskia P.; Saba, Yasaman; Cuellar-Partida, Gabriel; Amin, Najaf; Hilal, Saima; Nho, Kwangsik; Mirza-Schreiber, Nazanin; Arfanakis, Konstantinos; Becker, Diane M.; Ames, David; Goldman, Aaron L.; Lee, Phil H.; Boomsma, Dorret I.; Lovestone, Simon; Giddaluru, Sudheer; Le Hellard, Stephanie; Mattheisen, Manuel; Bohlken, Marc M.; Kasperaviciute, Dalia; Schmaal, Lianne; Lawrie, Stephen M.; Agartz, Ingrid; Walton, Esther; Tordesillas-Gutierrez, Diana; Davies, Gareth E.; Shin, Jean; Ipser, Jonathan C.; Vinke, Louis N.; Hoogman, Martine; Jia, Tianye; Burkhardt, Ralph; Klein, Marieke; Crivello, Fabrice; Janowitz, Deborah; Carmichael, Owen; Haukvik, Unn K.; Aribisala, Benjamin S.; Schmidt, Helena; Strike, Lachlan T.; Cheng, Ching-Yu; Risacher, Shannon L.; Pütz, Benno; Fleischman, Debra A.; Assareh, Amelia A.; Mattay, Venkata S.; Buckner, Randy L.; Mecocci, Patrizia; Dale, Anders M.; Cichon, Sven; Boks, Marco P.; Matarin, Mar; Penninx, Brenda W. J. H.; Calhoun, Vince D.; Chakravarty, M. Mallar; Marquand, Andre F.; Macare, Christine; Kharabian Masouleh, Shahrzad; Oosterlaan, Jaap; Amouyel, Philippe; Hegenscheid, Katrin; Rotter, Jerome I.; Schork, Andrew J.; Liewald, David C. M.; de Zubicaray, Greig I.; Wong, Tien Yin; Shen, Li; Sämann, Philipp G.; Brodaty, Henry; Roffman, Joshua L.; de Geus, Eco J. C.; Tsolaki, Magda; Erk, Susanne; van Eijk, Kristel R.; Cavalleri, Gianpiero L.; van der Wee, Nic J. A.; McIntosh, Andrew M.; Gollub, Randy L.; Bulayeva, Kazima B.; Bernard, Manon; Richards, Jennifer S.; Himali, Jayandra J.; Loeffler, Markus; Rommelse, Nanda; Hoffmann, Wolfgang; Westlye, Lars T.; Valdés Hernández, Maria C.; Hansell, Narelle K.; van Erp, Theo G. M.; Wolf, Christiane; Kwok, John B. J.; Vellas, Bruno; Heinz, Andreas; Olde Loohuis, Loes M.; Delanty, Norman; Ho, Beng-Choon; Ching, Christopher R. K.; Shumskaya, Elena; Singh, Baljeet; Hofman, Albert; van der Meer, Dennis; Homuth, Georg; Psaty, Bruce M.; Bastin, Mark E.; Montgomery, Grant W.; Foroud, Tatiana M.; Reppermund, Simone; Hottenga, Jouke-Jan; Simmons, Andrew; Meyer-Lindenberg, Andreas; Cahn, Wiepke; Whelan, Christopher D.; van Donkelaar, Marjolein M. J.; Yang, Qiong; Hosten, Norbert; Green, Robert C; Thalamuthu, Anbupalam; Mohnke, Sebastian; Hulshoff Pol, Hilleke E.; Lin, Honghuang; Jack, Clifford R.; Schofield, Peter R.; Mühleisen, Thomas W.; Maillard, Pauline; Potkin, Steven G.; Wen, Wei; Fletcher, Evan; Toga, Arthur W.; Gruber, Oliver; Huentelman, Matthew; Davey Smith, George; Launer, Lenore J.; Nyberg, Lars; Jönsson, Erik G.; Crespo-Facorro, Benedicto; Koen, Nastassja; Greve, Douglas N.; Uitterlinden, André G.; Weinberger, Daniel R.; Steen, Vidar M.; Fedko, Iryna O.; Groenewold, Nynke A.; Niessen, Wiro J.; Toro, Roberto; Tzourio, Christophe; Longstreth, William T.; Ikram, M. Kamran; Smoller, Jordan W.; van Tol, Marie-Jose; Sussmann, Jessika E.; Paus, Tomas; Lemaître, Hervé; Schroeter, Matthias L.; Mazoyer, Bernard; Andreassen, Ole A.; Holsboer, Florian; Depondt, Chantal; Veltman, Dick J.; Turner, Jessica A.; Pausova, Zdenka; Schumann, Gunter; van Rooij, Daan; Djurovic, Srdjan; Deary, Ian J.; McMahon, Katie L.; Müller-Myhsok, Bertram; Brouwer, Rachel M.; Soininen, Hilkka; Pandolfo, Massimo; Wassink, Thomas H.; Cheung, Joshua W.; Wolfers, Thomas; Martinot, Jean-Luc; Zwiers, Marcel P.; Nauck, Matthias; Melle, Ingrid; Martin, Nicholas G.; Kanai, Ryota; Westman, Eric; Kahn, René S.; Sisodiya, Sanjay M.; White, Tonya; Saremi, Arvin; van Bokhoven, Hans; Brunner, Han G.; Völzke, Henry; Wright, Margaret J.; van ‘t Ent, Dennis; Nöthen, Markus M.; Ophoff, Roel A.; Buitelaar, Jan K.; Fernández, Guillén; Sachdev, Perminder S.; Rietschel, Marcella; van Haren, Neeltje E. M.; Fisher, Simon E.; Beiser, Alexa S.; Francks, Clyde; Saykin, Andrew J.; Mather, Karen A.; Romanczuk-Seiferth, Nina; Hartman, Catharina A.; DeStefano, Anita L.; Heslenfeld, Dirk J.; Weiner, Michael W.; Walter, Henrik; Hoekstra, Pieter J.; Nyquist, Paul A.; Franke, Barbara; Bennett, David A.; Grabe, Hans J.; Johnson, Andrew D.; Chen, Christopher; van Duijn, Cornelia M.; Lopez, Oscar L.; Fornage, Myriam; Wardlaw, Joanna M.; Schmidt, Reinhold; DeCarli, Charles; De Jager, Philip L.; Villringer, Arno; Debette, Stéphanie; Gudnason, Vilmundur; Medland, Sarah E.; Shulman, Joshua M.; Thompson, Paul M.; Seshadri, Sudha; Ikram, M. Arfan; Medical and Molecular Genetics, School of Medicine
    Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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    Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
    (Springer Nature, 2019-03) 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.; Deniz Naranjo, Maria Candida; 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.; Benit, Yolanda A.; Holmes, Clive; Karamujić-Čomić, Hata; Frosch, Matthew P.; Thonberg, Hakan; Maier, Wolfgang; Roshchupkin, Gennady; 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, Lluís; Larson, Eric B.; Haapasalo, Annakaisa; Lawlor, Brian; Mosley, Thomas H.; Lipton, Richard B.; Solfrizzi, Vincenzo; Gill, Michael; Longstreth, W. T., Jr.; 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; Uitterlinden, A. G. Andre; Royall, Donald R.; Dufouil, Carole; Maletta, Raffaele Giovanni; de Rojas, Itziar; Sano, Mary; Brice, Alexis; Cecchetti, Roberta; St. George-Hyslop, Peter; 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, Ángel; 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, R.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; O'Donovan, Michael C.; 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.; Pathology and Laboratory Medicine, School of Medicine
    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.
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    A Multiancestral Genome-Wide Exome Array Study of Alzheimer Disease, Frontotemporal Dementia, and Progressive Supranuclear Palsy
    (2015-04) Chen, Jason A.; Wang, Qing; Davis-Turak, Jeremy; Li, Yun; Karydas, Anna M.; Hsu, Sandy C.; Sears, Renee L.; Chatzopoulou, Doxa; Huang, Alden Y.; Wojta, Kevin J.; Klein, Eric; Lee, Jason; Beekly, Duane L.; Boxer, Adam; Faber, Kelley M.; Haase, Claudia M.; Miller, Josh; Poon, Wayne W.; Rosen, Ami; Rosen, Howard; Sapozhnikova, Anna; Shapira, Jill; Varpetian, Arousiak; Foroud, Tatiana M.; Levenson, Robert W.; Levey, Allan I.; Kukull, Walter A.; Mendez, Mario F.; Ringman, John; Chui, Helena; Cotman, Carl; DeCarli, Charles; Miller, Bruce L.; Geschwind, Daniel H.; Coppola, Giovanni; Department of Medical and Molecular Genetics, IU School of Medicine
    Importance Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wide level. Objective To identify low-frequency coding variants that affect susceptibility to AD, FTD, and PSP. Design, Setting, and Participants We used the Illumina HumanExome BeadChip array to genotype a large number of variants (most of which are low-frequency coding variants) in a cohort of patients with neurodegenerative disease (224 with AD, 168 with FTD, and 48 with PSP) and in 224 control individuals without dementia enrolled between 2005-2012 from multiple centers participating in the Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease (GIFT) Study. An additional multiancestral replication cohort of 240 patients with AD and 240 controls without dementia was used to validate suggestive findings. Variant-level association testing and gene-based testing were performed. Main Outcomes and Measures Statistical association of genetic variants with clinical diagnosis of AD, FTD, and PSP. Results Genetic variants typed by the exome array explained 44%, 53%, and 57% of the total phenotypic variance of AD, FTD, and PSP, respectively. An association with the known AD gene ABCA7 was replicated in several ancestries (discovery P = .0049, European P = .041, African American P = .043, and Asian P = .027), suggesting that exonic variants within this gene modify AD susceptibility. In addition, 2 suggestive candidate genes, DYSF (P = 5.53 × 10−5) and PAXIP1 (P = 2.26 × 10−4), were highlighted in patients with AD and differentially expressed in AD brain. Corroborating evidence from other exome array studies and gene expression data points toward potential involvement of these genes in the pathogenesis of AD. Conclusions and Relevance Low-frequency coding variants with intermediate effect size may account for a significant fraction of the genetic susceptibility to AD and FTD. Furthermore, we found evidence that coding variants in the known susceptibility gene ABCA7, as well as candidate genes DYSF and PAXIP1, confer risk for AD.
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    Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel
    (American Medical Association, 2021-01-01) Kunkle, Brian W.; Schmidt, Michael; Klein, Hans-Ulrich; Naj, Adam C.; Hamilton-Nelson, Kara L.; Larson, Eric B.; Evans, Denis A.; De Jager, Phil L.; Crane, Paul K.; Buxbaum, Joe D.; Ertekin-Taner, Nilufer; Go, Rodney C.P.; Obisesan, Thomas O.; Kamboh, Ilyas; Bennett, David A.; Hall, Kathleen S.; Goate, Alison M.; Foroud, Tatiana M.; Martin, Eden R.; Wang, Li-Sao; Byrd, Goldie S.; Farrer, Lindsay A.; Haines, Jonathan L.; Schellenberg, Gerard D.; Mayeux, Richard; Pericak-Vance, Margaret A.; Reitz, Christiane; Graff-Radford, Neill R.; Martinez, Izri; Ayodele, Temitope; Logue, Mark W.; Cantwell, Laura B.; Jean-Francois, Melissa; Kuzma, Amanda B.; Adams, L.D.; Vance, Jeffery M.; Cuccaro, Michael L.; Chung, Jaeyoon; Mez, Jesse; Lunetta, Kathryn L.; Jun, Gyungah R.; Lopez, Oscar L.; Hendrie, Hugh C.; Reiman, Eric M.; Kowall, Neil W.; Leverenz, James B.; Small, Scott A.; Levey, Allan I.; Golde, Todd E.; Saykin, Andrew J.; Starks, Takiyah D.; Albert, Marilyn S.; Hyman, Bradley T.; Petersen, Ronald C.; Sano, Mary; Wisniewski, Thomas; Vassar, Robert; Kaye, Jeffrey A.; Henderson, Victor W.; DeCarli, Charles; LaFerla, Frank M.; Brewer, James B.; Miller, Bruce L.; Swerdlow, Russell H.; Van Eldik, Linda J.; Paulson, Henry L.; Trojanowski, John Q.; Chui, Helena C.; Rosenberg, Roger N.; Craft, Suzanne; Grabowski, Thomas J.; Asthana, Sanjay; Morris, John C.; Strittmatter, Stephen M.; Kukull, Walter A.; Psychiatry, School of Medicine
    Importance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, setting, and participants: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main outcomes and measures: Diagnosis of Alzheimer disease. Results: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10-7), near the immune response gene ALCAM (3q13; P = 9.3 × 10-7), within GPC6 (13q31; P = 4.1 × 10-7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and within VRK3 (19q13.33; P = 3.5 × 10-7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7 × 10-9) and 6 additional loci with suggestive significance (P ≤ 5 × 10-7) such as API5 at 11p12 (P = 8.8 × 10-8) and RBFOX1 at 16p13 (P = 5.4 × 10-7) were identified. Gene expression data from brain tissue demonstrate association of ALCAM, ARAP1, GPC6, and RBFOX1 with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and relevance: While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.
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    Novel genetic loci associated with hippocampal volume
    (SpringerNature, 2017-01-18) Hibar, Derrek P.; Adams, Hieab H.H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, Mallar; Chen, Qiang; Ching, Christopher R.K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C.M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M.; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J.; Van der Meer, Dennis; Van Donkelaar, Marjolein M. J.; Van Eijk, Kristel R.; Van Erp, Theo G.M.; Van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; De Craen, Anton J.M.; De Geus, Eco J.C.; De Jager, Philip L.; De Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H.H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Coon; Hoekstra, Pieter J.; Hoffman, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack Jr., Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Purohit, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Valdés Hernández, Maria C.; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; Van Haren, Neeltje E. M.; van't Ent, Dennis; Van Tol, Marie-Jose; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; Van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Arfan, M.; Department of Radiology and Imaging Sciences, IU School of Medicine
    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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    Relationship between baseline brain metabolism measured using [18F]FDG PET and memory and executive function in prodromal and early Alzheimer's disease
    (Springer, 2012) Habeck, Christian; Risacher, Shannon; Lee, Grace J.; Glymour, M. Maria; Mormino, Elizabeth; Mukherjee, Shubhabrata; Kim, Sungeun; Nho, Kwangsik; DeCarli, Charles; Saykin, Andrew J.; Crane, Paul K.; Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Differences in brain metabolism as measured by FDG-PET in prodromal and early Alzheimer's disease (AD) have been consistently observed, with a characteristic parietotemporal hypometabolic pattern. However, exploration of brain metabolic correlates of more nuanced measures of cognitive function has been rare, particularly in larger samples. We analyzed the relationship between resting brain metabolism and memory and executive functioning within diagnostic group on a voxel-wise basis in 86 people with AD, 185 people with mild cognitive impairment (MCI), and 86 healthy controls (HC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found positive associations within AD and MCI but not in HC. For MCI and AD, impaired executive functioning was associated with reduced parietotemporal metabolism, suggesting a pattern consistent with known AD-related hypometabolism. These associations suggest that decreased metabolic activity in the parietal and temporal lobes may underlie the executive function deficits in AD and MCI. For memory, hypometabolism in similar regions of the parietal and temporal lobes were significantly associated with reduced performance in the MCI group. However, for the AD group, memory performance was significantly associated with metabolism in frontal and orbitofrontal areas, suggesting the possibility of compensatory metabolic activity in these areas. Overall, the associations between brain metabolism and cognition in this study suggest the importance of parietal and temporal lobar regions in memory and executive function in the early stages of disease and an increased importance of frontal regions for memory with increasing impairment.
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    Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers
    (Wiley, 2022-06-29) Weiner, Michael W.; Harvey, Danielle; Landau, Susan M.; Veitch, Dallas P.; Neylan, Thomas C.; Grafman, Jordan H.; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford R., Jr.; Tosun, Duygu; Shaw, Leslie M.; Trojanowski, John Q.; Saykin, Andrew J.; Hayes, Jacqueline; DeCarli, Charles; Alzheimer’s Disease Neuroimaging Initiative; Department of Defense Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: Epidemiological studies report an association between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and clinically diagnosed Alzheimer's disease (AD). We examined the association between TBI/PTSD and biomarker-defined AD. Methods: We identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aβ) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years. Results: Exposure groups (TBI, PTSD, and TBI + PTSD) had higher prevalence of mild cognitive impairment (MCI: P < .0001) and worse Mini-Mental State Examination scores (PTSD: P = .008; TBI & PTSD: P = .009) than controls. There were no significant differences in other cognitive scores, MRI volumes, Aβ or tau accumulation, or in most longitudinal measures. Discussion: TBI and/or PTSD were not associated with elevated AD biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.
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    Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease
    (Wiley, 2022) Veitch, Dallas P.; Weiner, Michael W.; Aisen, Paul S.; Beckett, Laurel A.; DeCarli, Charles; Green, Robert C.; Harvey, Danielle; Jack, Clifford R., Jr.; Jagust, William; Landau, Susan M.; Morris, John C.; Okonkwo, Ozioma; Perrin, Richard J.; Petersen, Ronald C.; Rivera-Mindt, Monica; Saykin, Andrew J.; Shaw, Leslie M.; Toga, Arthur W.; Tosun, Duygu; Trojanowski, John Q.; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, biofluid biomarker and genetic data, and biofluid samples available to researchers, resulting in more than 3500 publications. This review covers studies from 2018 to 2020. Methods: We identified 1442 publications using ADNI data by conventional search methods and selected impactful studies for inclusion. Results: Disease progression studies supported pivotal roles for regional amyloid beta (Aβ) and tau deposition, and identified underlying genetic contributions to Alzheimer's disease (AD). Vascular disease, immune response, inflammation, resilience, and sex modulated disease course. Biologically coherent subgroups were identified at all clinical stages. Practical algorithms and methodological changes improved determination of Aβ status. Plasma Aβ, phosphorylated tau181, and neurofilament light were promising noninvasive biomarkers. Prognostic and diagnostic models were externally validated in ADNI but studies are limited by lack of ethnocultural cohort diversity. Discussion: ADNI has had a profound impact in improving clinical trials for AD.