title: Prediction of Alzheimer disease in subjects with amnestic and nonamnestic MCI.
abstract: OBJECTIVE
  To compare the predictive accuracy of β-amyloid (Aβ)1-42 and total tau in CSF, hippocampal volume (HCV), and APOE genotype for Alzheimer disease (AD)-type dementia in subjects with amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI).
  
  
  METHODS
  We selected 399 subjects with aMCI and 226 subjects with naMCI from a multicenter memory clinic-based cohort. We measured CSF Aβ1-42 and tau by ELISA (n = 231), HCV on MRI (n = 388), and APOE ε4 (n = 523). Follow-up was performed annually up to 5 years. Outcome measures were progression to AD-type dementia and cognitive decline.
  
  
  RESULTS
  At least 1 follow-up was available for 538 subjects (86%). One hundred thirty-two subjects with aMCI (38%) and 39 subjects with naMCI (20%) progressed to AD-type dementia after an average follow-up of 2.5 years. CSF Aβ1-42, tau, Aβ1-42/tau ratio, HCV, and APOE ε4 predicted AD-type dementia in each MCI subgroup with the same overall diagnostic accuracy. However, CSF Aβ1-42 concentration was higher and hippocampal atrophy less severe in subjects with naMCI compared with aMCI. This reduced the sensitivity but increased the specificity of these markers for AD-type dementia in subjects with naMCI.
  
  
  CONCLUSIONS
  AD biomarkers are useful to predict AD-type dementia in subjects with aMCI and naMCI. However, biomarkers might not be as sensitive for early diagnosis of AD in naMCI compared with aMCI. This may have implications for clinical implementation of the National Institute on Aging and Alzheimer's Association criteria.
authors: Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands. s.vos@maastrichtuniversity.nl
authors: Stephanie J B
authors: SJ
authors: Vos
authors: Ineke A
authors: IA
authors: van Rossum
authors: Frans
authors: F
authors: Verhey
authors: Dirk L
authors: DL
authors: Knol
authors: Hilkka
authors: H
authors: Soininen
authors: Lars-Olof
authors: LO
authors: Wahlund
authors: Harald
authors: H
authors: Hampel
authors: Magda
authors: M
authors: Tsolaki
authors: Lennart
authors: L
authors: Minthon
authors: Giovanni B
authors: GB
authors: Frisoni
authors: Lutz
authors: L
authors: Froelich
authors: Flavio
authors: F
authors: Nobili
authors: Wiesje
authors: W
authors: van der Flier
authors: Kaj
authors: K
authors: Blennow
authors: Robin
authors: R
authors: Wolz
authors: Philip
authors: P
authors: Scheltens
authors: Pieter Jelle
authors: PJ
authors: Visser
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D000647:Amnesia / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins