2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

摘要: 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 tracking of disease (AD). initial study, ADNI-1, enrolled 400 subjects with mild cognitive impairment (MCI), 200 AD, cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 competitive renewal, ADNI-2, which additional 550 participants will run until 2015. This article reviews all papers published since inception initiative summarizes results end 2013. major accomplishments ADNI have been as follows: (1) development standardized methods clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid (CSF) setting; (2) elucidation patterns rates change CSF biomarker measurements control subjects, MCI patients, AD patients. are largely consistent trajectories predicted β-amyloid cascade (Hardy, J Dis 2006;9(Suppl 3):151–3) tau-mediated neurodegeneration hypotheses whereas brain atrophy hypometabolism levels show but exhibit differing depending on region severity; (3) assessment alternative diagnostic categorization. Currently, best classifiers select combine optimum features from multiple modalities, including MRI, [ 18 F]-fluorodeoxyglucose-PET, amyloid PET, biomarkers, tests; (4) blood potentially noninvasive low-cost alternatives diagnosis α-syn biomarker; (5) AD. 42 tau, well PET may reflect earliest steps pathology mildly symptomatic or even nonsymptomatic leading candidates its preclinical stages; (6) improvement trial efficiency through identification most likely undergo imminent future decline use more sensitive outcome measures reduce sample sizes. Multimodal incorporating APOE status longitudinal MRI proved highly predictive decline. Refinements tests used such dementia rating-sum boxes further reduced sizes; (7) pioneering genome-wide association studies that leverage quantitative phenotypes, data, confirm recently identified loci, CR1, CLU , PICALM identify novel risk loci; (8) worldwide impact establishment ADNI-like programs Japan, Australia, Argentina, Taiwan, China, Korea, Europe, Italy; (9) understanding biology pathobiology aging, MCI, integration data stimulate research resolve controversies about competing etiopathogenesis thereby advancing efforts find disease-modifying drugs AD; (10) infrastructure allow sharing raw processed without embargo interested scientific investigators throughout world.