title: Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.
abstract: BACKGROUND
  The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI).
  
  
  METHODS
  Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms.
  
  
  RESULTS
  Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency.
  
  
  CONCLUSIONS
  These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.
authors.affiliation: *Medical Imaging Unit, Biomedical Engineering Department, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Bergamo †Laboratory of Epidemiology and Neuroimaging, IRCCS Fatebenefratelli, Brescia §Department of Decision Science, Bocconi University, Milan, Italy ‡Department of Engineering, University of Cambridge **Institute of Brain, Behaviour, and Mental Health University of Cambridge, Cambridge ∥Banner Alzheimer's Institute, Phoenix, AZ ¶Helen Wills Neuroscience Institute, University of California, Berkeley, CA #Hannover Medical School, Clinic for Nuclear Medicine, Hannover, Germany ††Departments of Internal Medicine and Psychiatry, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Caroli
authors.forename: Annapaola
authors.initials: A
authors.lastname: Prestia
authors.forename: Sara
authors.initials: S
authors.lastname: Wade
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Napatkamon
authors.initials: N
authors.lastname: Ayutyanont
authors.forename: Susan M
authors.initials: SM
authors.lastname: Landau
authors.forename: Cindee M
authors.initials: CM
authors.lastname: Madison
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haense
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002986:Clinical Trials as Topic; D003071:Cognition; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C075222:amyloid beta-protein (1-42); D019788:Fluorodeoxyglucose F18