title: Longitudinal change of biomarkers in cognitive decline.
abstract: OBJECTIVE
  To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD).
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative.
  
  
  METHODS
  A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007.
  
  
  METHODS
  Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker.
  
  
  RESULTS
  Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD.
  
  
  CONCLUSIONS
  Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.
authors.affiliation: Division of Epidemiology, University of California, Berkeley, 94720-3190, USA. rlo@berkeley.edu
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Lo
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000134:cerebrospinal fluid; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography / Q000379:methods; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019788:Fluorodeoxyglucose F18