Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI

Stephanie Vos*, Ineke A. van Rossum, Leah Burns, Dirk Knol, Philip Scheltens, Hilkka Soininen, Lars-Olof Wahlund, Harald Hampel, Magda Tsolaki, Lennart Minthon, Ron Handels, Gilbert L'Italien, Wiesje M. van der Flier, Pauline Aalten, Charlotte Teunissen, Frederik Barkhof, Kaj Blennow, Robin Wolz, Daniel Rueckert, Frans VerheyPieter Jelle Visser

*Corresponding author for this work

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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 (A beta)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 A beta 1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF A beta 1-42/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 A beta 1-42/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.
Original languageEnglish
Pages (from-to)2272-2281
JournalNeurobiology of Aging
Issue number10
Publication statusPublished - Oct 2012


  • Alzheimer's disease (AD)
  • Dementia
  • Mild cognitive impairment (MCI)
  • cerebrospinal fluid (CSF)
  • A beta 1-42
  • Tau
  • Magnetic resonance imaging (MRI)
  • Volumetry
  • Hippocampus
  • Diagnostic test sequence

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