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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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Details

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