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
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
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
N1 - Funding Information:
The DESCRIPA study was supported by European Community’s 5th Framework Programme contract number QLK-6-CT-2002-02455. Additional funding was provided by the Center for Translational Molecular Medicine ( www.ctmm.nl ) project LeARN (grant 02N-01 ; SV, RH), Bristol-Myers Squibb, and the European Community's 7th Framework Programme (FP7/2007–2013), grant agreement no 211696 (Lipididiet [IvR]), and grant agreement no 224328 (PredictAD [RW, DR]). The Alzheimer Center VUmc receives unrestricted funding from various sources through the VUmc Fonds.
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 (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 ncreased 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.
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 (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 ncreased 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.
KW - Alzheimer's disease (AD)
KW - Aβ1-42
KW - Cerebrospinal fluid (CSF)
KW - Dementia
KW - Diagnostic test sequence
KW - Hippocampus
KW - Magnetic resonance imaging (MRI)
KW - Mild cognitive impairment (MCI)
KW - Tau
KW - Volumetry
UR - http://www.scopus.com/inward/record.url?scp=84864383552&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2011.12.017
DO - 10.1016/j.neurobiolaging.2011.12.017
M3 - Article
C2 - 22264648
AN - SCOPUS:84864383552
SN - 0197-4580
VL - 33
SP - 2272
EP - 2281
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 10
ER -