title: Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI.
abstract: Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF Aβ1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF Aβ1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF Aβ1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD.
authors.affiliation: Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands. s.vos@maastrichtuniversity.nl
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vos
authors.forename: Ineke
authors.initials: I
authors.lastname: van Rossum
authors.forename: Leah
authors.initials: L
authors.lastname: Burns
authors.forename: Dirk
authors.initials: D
authors.lastname: Knol
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Ron
authors.initials: R
authors.lastname: Handels
authors.forename: Gilbert
authors.initials: G
authors.lastname: L'Italien
authors.forename: Wiesje
authors.initials: W
authors.lastname: van der Flier
authors.forename: Pauline
authors.initials: P
authors.lastname: Aalten
authors.forename: Charlotte
authors.initials: C
authors.lastname: Teunissen
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Robin
authors.initials: R
authors.lastname: Wolz
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueckert
authors.forename: Frans
authors.initials: F
authors.lastname: Verhey
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 / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D062706:Prodromal Symptoms; 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