The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception.
Michael W. Weiner,Michael W. Weiner,Dallas P. Veitch,Paul S. Aisen,Laurel A. Beckett,Nigel J. Cairns,Robert C. Green,Danielle J Harvey,Clifford R. Jack,William J. Jagust,Enchi Liu,John C. Morris,Ronald C. Petersen,Andrew J. Saykin,Mark E. Schmidt,Leslie M. Shaw,Judith Siuciak,Holly Soares,Arthur W. Toga,John Q. Trojanowski +19 more
TLDR
The major accomplishments of ADNI have been the development of standardized methods for clinical tests, magnetic resonance imaging, positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting, and the improvement of clinical trial efficiency.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, [(18)F]-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.read more
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The cognitive neuroscience of ageing
TL;DR: Current trends and unresolved issues in the cognitive neuroscience of ageing are discussed and it is less clear how age differences in brain activity relate to cognitive performance.
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Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis
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TL;DR: Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date.
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The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
Paul M. Thompson,Jason L. Stein,Sarah E. Medland,Derrek P. Hibar,Alejandro Arias Vasquez,Miguel E. Rentería,Roberto Toro,Neda Jahanshad,Gunter Schumann,Barbara Franke,Margaret J. Wright,Nicholas G. Martin,Ingrid Agartz,Ingrid Agartz,Martin Alda,Saud Alhusaini,Saud Alhusaini,Laura Almasy,Jorge R. C. Almeida,Jorge R. C. Almeida,Jorge R. C. Almeida,Kathryn I. Alpert,Nancy C. Andreasen,Ole A. Andreassen,Liana G. Apostolova,Katja Appel,Nicola J. Armstrong,Benjamin S. Aribisala,Mark E. Bastin,Michael Bauer,Carrie E. Bearden,Ørjan Bergmann,Elisabeth B. Binder,John Blangero,HJ Bockholt,Erlend Bøen,Catherine Bois,Dorret I. Boomsma,Tom Booth,Ian Bowman,Janita Bralten,Rachel M. Brouwer,Han G. Brunner,David G. Brohawn,Randy L. Buckner,Jan K. Buitelaar,Kazima B. Bulayeva,Juan R. Bustillo,Vince D. Calhoun,Vince D. Calhoun,Dara M. Cannon,Rita M. Cantor,Melanie A. Carless,Xavier Caseras,Gianpiero L. Cavalleri,M. Mallar Chakravarty,Kiki D. Chang,Christopher R.K. Ching,Andrea Christoforou,Andrea Christoforou,Sven Cichon,Sven Cichon,Vincent P. Clark,Patricia J. Conrod,Patricia J. Conrod,Giovanni Coppola,Benedicto Crespo-Facorro,Joanne E. Curran,Michael Czisch,Ian J. Deary,Eco J. C. de Geus,Anouk den Braber,G. Delvecchio,Chantal Depondt,Lieuwe de Haan,Lieuwe de Haan,Greig I. de Zubicaray,Danai Dima,Rali Dimitrova,Srdjan Djurovic,Hong-Wei Dong,Gary Donohoe,Gary Donohoe,Ravindranath Duggirala,Thomas D. Dyer,Stefan Ehrlich,Stefan Ehrlich,Carl Johan Ekman,Torbjørn Elvsåshagen,Louise Emsell,Susanne Erk,Thomas Espeseth,Jesen Fagerness,Scott C. Fears,Iryna O. Fedko,Guillén Fernández,Simon E. Fisher,Simon E. Fisher,Tatiana Foroud,Peter T. Fox,Clyde Francks,Clyde Francks,Sophia Frangou,Eva Maria Frey,Thomas Frodl,Thomas Frodl,Vincent Frouin,Hugh Garavan,Sudheer Giddaluru,David C. Glahn,Beata R. Godlewska,Rita Z. Goldstein,Randy L. Gollub,Hans J. Grabe,Oliver Grimm,Oliver Gruber,Tulio Guadalupe,Raquel E. Gur,Ruben C. Gur,Ruben C. Gur,Harald H H Göring,Saskia P. Hagenaars,Tomas Hajek,Geoffrey B. Hall,Jeremy Hall,Jeremy Hall,John Hardy,Catharina A. Hartman,Johanna Hass,Sean N. Hatton,Unn K. Haukvik,K Hegenscheid,Andreas Heinz,Ian B. Hickie,Beng-Choon Ho,D. Hoehn,Pieter J. Hoekstra,Marisa O. Hollinshead,Avram J. Holmes,Georg Homuth,Martine Hoogman,L. Elliot Hong,Norbert Hosten,Jouke-Jan Hottenga,Hilleke E. Hulshoff Pol,Kristy S. Hwang,Clifford R. Jack,Mark Jenkinson,Caroline Johnston,Caroline Johnston,Erik G. Jönsson,René S. Kahn,Dalia Kasperaviciute,Sinead Kelly,Sungeun Kim,Peter Kochunov,Laura Koenders,Laura Koenders,Bernd Krämer,John B.J. Kwok,John B.J. Kwok,Jim Lagopoulos,Gonzalo Laje,Mikael Landén,Mikael Landén,Bennett A. Landman,John Lauriello,Stephen M. Lawrie,Phil Lee,Phil Lee,Stephanie Le Hellard,Stephanie Le Hellard,Herve Lemaitre,Cassandra D. Leonardo,Chiang shan Li,Benny Liberg,David C. Liewald,Xinmin Liu,Xinmin Liu,Lorna M. 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