The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception |
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| Institution: | 1. Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA;2. Department of Radiology, University of California, San Francisco, CA, USA;3. Department of Medicine, University of California, San Francisco, CA, USA;4. Department of Psychiatry, University of California, San Francisco, CA, USA;5. Department of Neurology, University of California, San Francisco, CA, USA;6. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA;7. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA;8. Knight Alzheimer''s Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA;9. Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA;10. Division of Genetics, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;11. Department of Radiology, Mayo Clinic, Rochester, MN, USA;12. Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA;13. Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA;14. Department of Neurology, Mayo Clinic, Rochester, MN, USA;15. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA;p. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA;q. Neuroscience Therapeutic Area, Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium;r. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;s. The Biomarkers Consortium, Foundation for the National Institutes of Health, Bethesda, MD, USA;t. Clinical Biomarkers, Bristol-Myers Squibb, Wallingford, CT, USA;u. Laboratory of Neuroimaging, Department of Neurology, School of Medicine, University of California Los Angeles, Los Angeles, CA, USA;v. Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;w. Alzheimer''s Disease Core Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;x. Udall Parkinson''s Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;y. Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;1. Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA;2. Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA;3. Banner Alzheimer Institute, Phoenix, AZ, USA;4. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA;5. Department of Neurology, Center for Alzheimer''s Care, Imaging and Research, University of Utah, Salt Lake City, UT, USA;1. Department of Psychiatry, University of California–San Francisco, San Francisco, CA, USA;2. Department of Neurology and Center for Neuroscience, University of California–Davis, Sacramento, CA, USA;3. Helen Wills Neuroscience Institute, University of California–Berkeley, Berkeley, CA, USA;4. Division of Biostatistics, Department of Public Health Sciences, University of California–Davis, Davis, CA, USA;1. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA;2. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA;3. Department of Neurosciences, University of California, San Diego, CA, USA;1. Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA;2. Department of Radiology, University of California, San Francisco, CA, USA;3. Department of Medicine, University of California, San Francisco, CA, USA;4. Department of Psychiatry, University of California, San Francisco, CA, USA;5. Department of Neurology, University of California, San Francisco, CA, USA;6. Alzheimer''s Therapeutic Research Institute, University of Southern California, San Diego, CA, USA;7. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA;8. Knight Alzheimer''s Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA;9. Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA;10. Division of Genetics, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;11. Department of Radiology, Mayo Clinic, Rochester, MN, USA;12. Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA;13. Department of Neurology, Mayo Clinic, Rochester, MN, USA;14. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA;15. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA;p. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;q. Laboratory of Neuroimaging, Institute of Neuroimaging and Informatics, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA;r. Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;s. Alzheimer''s Disease Core Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;t. Udall Parkinson''s Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;1. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;2. School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA;3. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA |
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| Abstract: | 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 study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. 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 consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated 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 combine optimum features from multiple modalities, including MRI, 18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 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; (5) 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. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants. |
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