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Abstract
There is well-documented evidence of brain network differences between individuals with Alzheimer’s disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitudinal ADNI data on the whole brain to jointly compute the brain network at baseline and one-year using a state of the art approach that pools information across both time points to yield distinct visit-specific networks for the AD and HC cohorts, resulting in more accurate inferences. We perform a multiscale comparison of the AD and HC networks in terms of global network metrics as well as at the more granular level of resting state networks defined under a whole brain parcellation. Our analysis illustrates a decrease in small-worldedness in the AD group at both the time points and also identifies more local network features and hub nodes that are disrupted due to the progression of AD. We also obtain high reproducibility of the HC network across visits. On the other hand, a separate estimation of the networks at each visit using standard graphical approaches reveals fewer meaningful differences and lower reproducibility.
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; Lukemire, Joshua 1 ; Wang, Yikai 1 ; Guo, Ying 1 ; Weiner, Michael W 2 ; Schuff, Norbert 3 ; Rosen, Howard J 2 ; Miller, Bruce L 2 ; Neylan, Thomas 2 ; Hayes, Jacqueline 2 ; Finley, Shannon 2 ; Aisen, Paul 4 ; Khachaturian, Zaven 5 ; Thomas, Ronald G 4 ; Donohue, Michael 4 ; Walter, Sarah 4 ; Gessert, Devon 4 ; Sather, Tamie 4 ; Jiminez, Gus 4 ; Thal, Leon 4 ; Brewer, James 4 ; Vanderswag, Helen 4 ; Fleisher, Adam 4 ; Davis, Melissa 4 ; Morrison, Rosemary 4 ; Petersen, Ronald 6 ; Jack, Clifford R 6 ; Bernstein, Matthew 6 ; Borowski, Bret 6 ; Gunter, Jeff 6 ; Senjem, Matt 6 ; Vemuri, Prashanthi 6 ; Jones, David 6 ; Kantarci, Kejal 6 ; Ward, Chad 6 ; Mason, Sara S 6 ; Albers, Colleen S 6 ; Knopman, David 6 ; Johnson, Kris 6 ; Jagust, William 7 ; Landau, Susan 7 ; Trojanowki, John Q 8 ; Shaw, Leslie M 8 ; Lee, Virginia 8 ; Korecka, Magdalena 8 ; Figurski, Michal 8 ; Arnold, Steven E 8 ; Karlawish, Jason H 8 ; Wolk, David 8 ; Toga, Arthur W 9 ; Crawford, Karen 9 ; Neu, Scott 9 ; Schneider, Lon S 9 ; Pawluczyk, Sonia 9 ; Beccera, Mauricio 9 ; Liberty Teodoro 9 ; Spann, Bryan M 9 ; Beckett, Laurel 10 ; Harvey, Danielle 10 ; Fletcher, Evan 10 ; Carmichael, Owen 10 ; Olichney, John 10 ; DeCarli, Charles 10 ; Green, Robert C 11 ; Sperling, Reisa A 11 ; Johnson, Keith A 11 ; Marshall, Gad 11 ; Frey, Meghan 11 ; Lane, Barton 11 ; Rosen, Allyson 11 ; Tinklenberg, Jared 11 ; Saykin, Andrew J 12 ; Foroud, Tatiana M 12 ; Shen, Li 12 ; Faber, Kelley 12 ; Kim, Sungeun 12 ; Nho, Kwangsik 12 ; Farlow, Martin R 12 ; Hake, AnnMarie 12 ; Matthews, Brandy R 12 ; Herring, Scott 12 ; Hunt, Cynthia 12 ; Morris, John 13 ; Raichle, Marc 13 ; Holtzman, Davie 13 ; Cairns, Nigel J 13 ; Householder, Erin 13 ; Taylor-Reinwald, Lisa 13 ; Ances, Beau 13 ; Carroll, Maria 13 ; Leon, Sue 13 ; Mintun, Mark A 13 ; Schneider, Stacy 13 ; Oliver, Angela 13 ; Raudin, Lisa 14 ; Sorensen, Greg 15 ; Kuller, Lew 16 ; Mathis, Chet 16 ; Lopez, Oscar L 16 ; Oakley, MaryAnn 16 ; Paul, Steven 17 ; Relkin, Norman 17 ; Chaing, Gloria 17 ; Davies, Peter 18 ; Fillit, Howard 19 ; Hefti, Franz 20 ; Mesulam, M Marcel 21 ; Kerwin, Diana 21 ; Marek-Marsel Mesulam 21 ; Lipowski, Kristine 21 ; Chuang-Kuo, Wu 21 ; Johnson, Nancy 21 ; Grafman, Jordan 21 ; Potter, William 22 ; Snyder, Peter 23 ; Schwartz, Adam 24 ; Montine, Tom 25 ; Peskind, Elaine R 25 ; Fox, Nick 26 ; Thompson, Paul 27 ; Apostolova, Liana 27 ; Tingus, Kathleen 27 ; Woo, Ellen 27 ; Silverman, Daniel H S 27 ; Lu, Po H 27 ; Bartzokis, George 27 ; Koeppe, Robert A 28 ; Heidebrink, Judith L 28 ; Lord, Joanne L 28 ; Potkin, Steven G 28 ; Preda, Adrian 28 ; Nguyenv, Dana 28 ; Foster, Norm 29 ; Reiman, Eric M 30 ; Chen, Kewei 30 ; Tariot, Pierre 30 ; Reeder, Stephanie 30 ; Potkin, Steven 31 ; Mulnard, Ruth A 31 ; Thai, Gaby 31 ; Mc-Adams-Ortiz, Catherine 31 ; Buckholtz, Neil 32 ; Hsiao, John 32 ; Albert, Marylyn 33 ; Albert, Marilyn 33 ; Onyike, Chiadi 33 ; Daniel D’Agostino 33 ; Kielb, Stephanie 33 ; Simpson, Donna M 33 ; Frank, Richard 34 ; Kaye, Jeffrey 35 ; Quinn, Joseph 35 ; Lind, Betty 35 ; Carter, Raina 35 ; Dolen, Sara 35 ; Doody, Rachelle S 36 ; Villanueva-Meyer, Javier 36 ; Chowdhury, Munir 36 ; Rountree, Susan 36 ; Dang, Mimi 36 ; Stern, Yaakov 36 ; Honig, Lawrence S 36 ; Bell, Karen L 36 ; Marson, Daniel 37 ; Griffith, Randall 37 ; Clark, David 37 ; Geldmacher, David 37 ; Brockington, John 37 ; Roberson, Erik 37 ; Grossman, Hillel 38 ; Mitsis, Effie 38 ; Leyla de Toledo-Morrell 39 ; Shah, Raj C 39 ; Fleischman, Debra 39 ; Arfanakis, Konstantinos 39 ; Duara, Ranjan 40 ; Varon, Daniel 40 ; Greig, Maria T 40 ; Roberts, Peggy 40 ; Galvin, James E 41 ; Cerbone, Brittany 41 ; Michel, Christina A 41 ; Rusinek, Henry 41 ; de Leon, Mony J 41 ; Glodzik, Lidia 41 ; De Santi, Susan 41 ; Doraiswamy, P Murali 42 ; Petrella, Jeffrey R 42 ; Wong, Terence Z 42 ; James, Olga 42 ; Smith, Charles D 43 ; Jicha, Greg 43 ; Hardy, Peter 43 ; Sinha, Partha 43 ; Oates, Elizabeth 43 ; Conrad, Gary 43 ; Porsteinsson, Anton P 44 ; Goldstein, Bonnie S 44 ; Kim, Martin 44 ; Makino, Kelly M 44 ; M Saleem Ismail 44 ; Brand, Connie 44 ; Womack, Kyle 45 ; Mathews, Dana 45 ; Quiceno, Mary 45 ; Diaz-Arrastia, Ramon 45 ; King, Richard 45 ; Weiner, Myron 45 ; Martin-Cook, Kristen 45 ; DeVous, Michael 45 ; Levey, Allan I 46 ; Lah, James J 46 ; Cellar, Janet S 46 ; Burns, Jeffrey M 47 ; Anderson, Heather S 47 ; Swerdlow, Russell H 47 ; Graff-Radford, Neill R 48 ; Parfitt, Francine 48 ; Kendall, Tracy 48 ; Johnson, Heather 48 ; van Dyck, Christopher H 49 ; Carson, Richard E 49 ; MacAvoy, Martha G 49 ; Chertkow, Howard 50 ; Bergman, Howard 50 ; Hosein, Chris 50 ; Black, Sandra 51 ; Stefanovic, Bojana 51 ; Caldwell, Curtis 51 ; Hsiung, Ging-Yuek Robin 52 ; Feldman, Howard 52 ; Mudge, Benita 52 ; Assaly, Michele 52 ; Kertesz, Andrew 53 ; Rogers, John 53 ; Bernick, Charles 53 ; Munic, Donna 53 ; Finger, Elizabether 54 ; Pasternak, Stephen 54 ; Rachinsky, Irina 54 ; Drost, Dick 54 ; Sadowsky, Carl 55 ; Martinez, Walter 55 ; Villena, Teresa 55 ; Turner, Raymond Scott 56 ; Johnson, Kathleen 56 ; Reynolds, Brigid 56 ; Sabbagh, Marwan N 57 ; Belden, Christine M 57 ; Jacobson, Sandra A 57 ; Sirrel, Sherye A 57 ; Kowall, Neil 58 ; Killiany, Ronald 58 ; Budson, Andrew E 58 ; Norbash, Alexander 58 ; Johnson, Patricia Lynn 58 ; Allard, Joanne 59 ; Lerner, Alan 60 ; Ogrocki, Paula 60 ; Hudson, Leon 60 ; Kittur, Smita 61 ; Borrie, Michael 62 ; T-Y, Lee 62 ; Bartha, Rob 62 ; Johnson, Sterling 63 ; Asthana, Sanjay 63 ; Carlsson, Cynthia M 63 ; Fruehling, J Jay 63 ; Harding, Sandra 63 ; Bates, Vernice 64 ; Capote, Horacio 64 ; Rainka, Michelle 64 ; Scharre, Douglas W 65 ; Kataki, Maria 65 ; Adeli, Anahita 65 ; Petrie, Eric C 65 ; Li, Gail 65 ; Zimmerman, Earl A 66 ; Celmins, Dzintra 66 ; Brown, Alice D 66 ; Pearlson, Godfrey D 67 ; Blank, Karen 67 ; Anderson, Karen 67 ; Santulli, Robert B 68 ; Kitzmiller, Tamar J 68 ; Schwartz, Eben S 68 ; Sink, Kaycee M 69 ; Williamson, Jeff D 69 ; Garg, Pradeep 69 ; Watkins, Franklin 69 ; Ott, Brian R 70 ; Querfurth, Henry 70 ; Tremont, Geoffrey 70 ; Salloway, Stephen 71 ; Malloy, Paul 71 ; Correia, Stephen 71 ; Mintzer, Jacobo 72 ; Spicer, Kenneth 72 ; Bachman, David 72 ; Massoglia, Dino 72 ; Pomara, Nunzio 73 ; Hernando, Raymundo 73 ; Sarrael, Antero 73 ; Schultz, Susan K 74 ; Boles Ponto, Laura L 74 ; Shim, Hyungsub 74 ; Smith, Karen Elizabeth 74 ; Smith, Amanda 75 ; Fargher, Kristin 75 ; Balebail, Ashok Raj 75 ; Friedl, Karl 76 ; Yesavage, Jerome A 77 ; Taylor, Joy L 77 ; Furst, Ansgar J 77 1 Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Ga, USA
2 UC San Francisco, California, USA
3 UC San Francisco, California, USA; UC Davis, California, USA
4 UC San Diego, California, USA
5 UC San Diego, California, USA; Prevent Alzheimer’s Disease, Rockville, Maryland, USA
6 Mayo Clinic, Rochester, New York, USA
7 UC Berkeley, California, USA
8 UPenn, Philadelphia, Pennsylvania, USA
9 USC, Los Angeles, California, USA
10 UC Davis, California, USA
11 Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts, USA
12 Indiana University, Bloomington, Indiana, USA
13 Washington University St Louis, Missouri, USA
14 Prevent Alzheimer’s Disease, Rockville, Maryland, USA
15 Siemens, Munich, Germany
16 University of Pittsburg, Pennsylvania, USA
17 Cornell University, Ithaca, New York, USA
18 Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA
19 AD Drug Discovery Foundation, New York City, New York, USA
20 Acumen Pharmaceuticals, Livermore, California, USA
21 Northwestern University, Evanston and Chicago, Illinois, USA
22 National Institute of Mental Health, Rockville, Maryland, USA
23 Brown University, Providence, Rhode Island, USA
24 Eli Lilly, Indianapolis, Indiana, USA
25 University of Washington, Seattle, Washington, USA
26 University of London, London, England
27 UCLA, Los Angeles, California, USA
28 University of Michigan, Ann Arbor, Michigan, USA
29 University of Utah, Salt Lake, Utah, USA
30 Banner Alzheimer’s Institute, Phoenix, Arizona, USA
31 UC Irvine, Irvine, California, USA
32 National Institute on Aging, Bethesda, Maryland, USA
33 Johns Hopkins University, Baltimore, Maryland, USA
34 Richard Frank Consulting, Washington, DC, USA
35 Oregon Health and Science University, Portland, Oregon, USA
36 Baylor College of Medicine, Houston, Texas, USA
37 University of Alabama, Birmingham, Alabama, USA
38 Mount Sinai School of Medicine, New York City, New York, USA
39 Rush University Medical Center, Chicago, Illinois, USA
40 Wien Center, Miami, Florida, USA
41 New York University, New York City, New York, USA
42 Duke University Medical Center, Durham, North Carolina, USA
43 University of Kentucky, Lexington, Kentucky, USA
44 University of Rochester Medical Center, Rochester, New York, USA
45 University of Texas Southwestern Medical School, Dallas, Texas, USA
46 Emory University, Atlanta, Georgia, USA
47 University of Kansas, Medical Center, Kansas City, Kansas, USA
48 Mayo Clinic, Jacksonville, Florida, USA
49 Yale University School of Medicine, New Haven, Connecticut, USA
50 McGill University/Montreal-Jewish General Hospital, Montreal, Quebec, Canada
51 Sunnybrook Health Sciences, Toronto, Ontario, Canada
52 U.B.C. Clinic for AD & Related Disorders, Vancouver, British Columbia, Canada
53 Cognitive Neurology–St Joseph’s, London, Ontario, Canada
54 St Joseph’s Health Care, London, Ontario, Canada
55 Premiere Research Institute, Palm Beach Neurology, Miami, Florida, USA
56 Georgetown University Medical Center, Washington, DC, USA
57 Banner Sun Health Research Institute, Sun City, Arizona, USA
58 Boston University, Boston, Massachusetts, USA
59 Howard University, Washington, DC, USA
60 Case Western Reserve University, Cleveland, Ohio, USA
61 Neurological Care of CNY, Liverpool, New York, USA
62 Parkwood Hospital, London, Ontario, USA
63 University of Wisconsin, Madison, Wisconsin, USA
64 Dent Neurologic Institute, Amherst, New York, USA
65 Ohio State University, Columbus, Ohio, USA
66 Albany Medical College, Albany, New York, USA
67 Hartford Hospital, Olin Neuropsychiatry Research Center, Hartford, Connecticut, USA
68 Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
69 Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA
70 Rhode Island Hospital, Providence, Rhode Island, USA
71 Butler Hospital, Providence, Rhode Island, USA
72 Medical University South Carolina, Charleston, South Carolina, USA
73 Nathan Kline Institute, Orangeburg, New York, USA
74 University of Iowa College of Medicine, Iowa City, Iowa, USA
75 University of South Florida: USF Health Byrd Alzheimer’s Institute, Tampa, Florida, USA
76 Department of Defense, Arlington, Virginia, USA
77 Stanford University, Stanford, California, USA




