title: Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease.
abstract: BACKGROUND
  It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline.
  
  
  METHODS
  526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values.
  
  
  RESULTS
  About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients.
  
  
  CONCLUSIONS
  For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.
authors.affiliation: Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR; Department of Neurology, University of Michigan, Ann Arbor, MI; Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI. Electronic address: dodgeh@ohsu.edu.
authors.forename: Hiroko H
authors.initials: HH
authors.lastname: Dodge
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Public Health Sciences, University of California, Davis, CA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Harvey
authors.affiliation: Department of Public Health Sciences, University of California, Davis, CA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR; Portland Veteran Affairs Medical Center, Portland, OR.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Silbert
authors.affiliation: Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR; Portland Veteran Affairs Medical Center, Portland, OR.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kaye
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI; Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI; Neurology Service and Geriatric Research, Education and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18
keywords: ADNI; ADNI-exe; ADNI-mem; Biomarker; Biomarker progressions; Cognitive declines; FDG-PET; MCI; MRI volume