title: The Alzheimer's Disease Neuroimaging Initiative: Annual change in biomarkers and clinical outcomes.
abstract: BACKGROUND
  The Alzheimer's Disease Neuroimaging Initiative Phase 1 (ADNI-1) is a multisite prospective study designed to examine potential cerebrospinal fluid and imaging markers of Alzheimer's disease (AD) and their relationship to cognitive change. The objective of this study was to provide a global summary of the overall results and patterns of change observed in candidate markers and clinical measures over the first 2 years of follow-up.
  
  
  METHODS
  Change was summarized for 210 normal controls, 357 mild cognitive impairment, and 162 AD subjects, with baseline and at least one cognitive follow-up assessment. Repeated measures and survival models were used to assess baseline biomarker levels as predictors. Potential for improving clinical trials was assessed by comparison of precision of markers for capturing change in hypothetical trial designs.
  
  
  RESULTS
  The first 12 months of complete data on ADNI participants demonstrated the potential for substantial advances in characterizing trajectories of change in a range of biomarkers and clinical outcomes, examining their relationship and timing, and assessing the potential for improvements in clinical trial design. Reduced metabolism and greater brain atrophy in the mild cognitive impairment at baseline are associated with more rapid cognitive decline and a higher rate of conversion to AD. Use of biomarkers as study entry criteria or as outcomes could reduce the number of participants required for clinical trials.
  
  
  CONCLUSIONS
  Analyses and comparisons of ADNI data strongly support the hypothesis that measurable change occurs in cerebrospinal fluid, positron emission tomography, and magnetic resonance imaging well in advance of the actual diagnosis of AD.
authors.affiliation: Department of Public Health Sciences, University of California, Davis, CA, USA. labeckett@ucdavis.edu
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Beckett
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Anthony
authors.initials: A
authors.lastname: Gamst
authors.forename: Michael
authors.initials: M
authors.lastname: Donohue
authors.forename: John
authors.initials: J
authors.lastname: Kornak
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Julie H
authors.initials: JH
authors.lastname: Kuo
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003952:Diagnostic Imaging; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011877:Radionuclide Imaging
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
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