title: Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease.
abstract: BACKGROUND
  We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD).
  
  
  METHODS
  We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132).
  
  
  RESULTS
  CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage.
  
  
  CONCLUSIONS
  This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.
authors.affiliation: Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands. Electronic address: d.bertens@vumc.nl.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bertens
authors.affiliation: Department of Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.affiliation: Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience (MHeNS), Alzheimer Centre Limburg, University Medical Centre, Maastricht, The Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer's disease; Asymptomatic; Biomarkers; Cognitive markers; Dementia; Longitudinal; MCI; Observational