{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T16:05:47Z","timestamp":1794413147674,"version":"4.9.1"},"reference-count":545,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI\u20101, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI\u20101 was extended by a 2\u2010year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI\u20102, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by \u03b2\u2010amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151\u20133) and tau\u2010mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [\n                      <jats:sup>18<\/jats:sup>\n                      F]\u2010fluorodeoxyglucose\u2010PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low\u2010cost alternatives to CSF biomarkers for AD diagnosis and the assessment of \u03b1\u2010syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, \u03b2\u2010amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating\n                      <jats:italic>APOE<\/jats:italic>\n                      status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating\u2010sum of boxes further reduced sample sizes; (7) the pioneering of genome\u2010wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci,\n                      <jats:italic>CR1, CLU<\/jats:italic>\n                      , and\n                      <jats:italic>PICALM<\/jats:italic>\n                      and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI\u2010like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease\u2010modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2014.11.001","type":"journal-article","created":{"date-parts":[[2015,6,12]],"date-time":"2015-06-12T04:49:51Z","timestamp":1434084591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":310,"title":["2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A\u00a0review of papers published since its inception"],"prefix":"10.1002","volume":"11","author":[{"given":"Michael W.","family":"Weiner","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs Medical Center Center for Imaging of Neurodegenerative Diseases  San Francisco CA USA"},{"name":"Department of Radiology University of California  San Francisco CA USA"},{"name":"Department of Medicine University of California  San Francisco CA USA"},{"name":"Department of Psychiatry University of California  San Francisco CA USA"},{"name":"Department of Neurology University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas P.","family":"Veitch","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center Center for Imaging of Neurodegenerative Diseases  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Aisen","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel A.","family":"Beckett","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences University of California  Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel J.","family":"Cairns","sequence":"additional","affiliation":[{"name":"Knight Alzheimer's Disease Research Center Washington University School of Medicine  Saint Louis MO USA"},{"name":"Department of Neurology Washington University School of Medicine  Saint Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Cedarbaum","sequence":"additional","affiliation":[{"name":"Neurology Early Clinical Development Biogen Idec  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Harvey","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences University of California  Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Jagust","sequence":"additional","affiliation":[{"name":"Helen Wills Neuroscience Institute University of California Berkeley  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Luthman","sequence":"additional","affiliation":[{"name":"Neuroscience Clinical Development, Neuroscience &amp; General Medicine Product Creation Unit Eisai Inc.  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