TY - JOUR
T1 - Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI
AU - Vos, Stephanie
AU - van Rossum, Ineke A.
AU - Burns, Leah
AU - Knol, Dirk
AU - Scheltens, Philip
AU - Soininen, Hilkka
AU - Wahlund, Lars-Olof
AU - Hampel, Harald
AU - Tsolaki, Magda
AU - Minthon, Lennart
AU - Handels, Ron
AU - L'Italien, Gilbert
AU - van der Flier, Wiesje M.
AU - Aalten, Pauline
AU - Teunissen, Charlotte
AU - Barkhof, Frederik
AU - Blennow, Kaj
AU - Wolz, Robin
AU - Rueckert, Daniel
AU - Verhey, Frans
AU - Visser, Pieter Jelle
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Alzheimer's disease (AD)
KW - Dementia
KW - Mild cognitive impairment (MCI)
KW - cerebrospinal fluid (CSF)
KW - A beta 1-42
KW - Tau
KW - Magnetic resonance imaging (MRI)
KW - Volumetry
KW - Hippocampus
KW - Diagnostic test sequence
U2 - 10.1016/j.neurobiolaging.2011.12.017
DO - 10.1016/j.neurobiolaging.2011.12.017
M3 - Article
SN - 0197-4580
VL - 33
SP - 2272
EP - 2281
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 10
ER -