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

NEUROBIOLOGY OF AGING

卷:33

Article

Vos, Stephanie¹  van Rossum, Ineke²  Burns, Leah³  Knol, Dirk⁴  Scheltens, Philip²  Soininen, Hilkka^5,6  Wahlund, Lars-Olof⁷  Hampel, Harald⁸  Tsolaki, Magda⁹  Minthon, Lennart¹⁰  Handels, Ron¹  L'Italien, Gilbert³  van der Flier, Wiesje²  Aalten, Pauline¹  Teunissen, Charlotte¹¹  Barkhof, Frederik¹²  Blennow, Kaj¹³  Wolz, Robin¹⁴  Rueckert, Daniel¹⁴  Verhey, Frans¹  Visser, Pieter Jelle^1,2 

[1] Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, Alzheimer Ctr Limburg, NL-6200 MD Maastricht, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, Amsterdam, Netherlands

[3] Bristol Myers Squibb Co, Wallingford, CT 06492 USA

[4] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands

[5] Univ Eastern Finland, Dept Neurol, Kuopio, Finland

[6] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland

[7] Karolinska Univ Hosp, Karolinska Inst, Sect Clin Geriatr, Dept NVS, Huddinge, Sweden

[8] Goethe Univ, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany

[9] Aristotle Univ Thessaloniki, Memory & Dementia Ctr, Dept Neurol 3, G Papanicolaou Gen Hosp, GR-54006 Thessaloniki, Greece

[10] Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden

[11] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Amsterdam, Netherlands

[12] Vrije Univ Amsterdam, Med Ctr, Dept Radiol, Amsterdam, Netherlands

[13] Gothenburg Univ, Sahlgrenska Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[14] Univ London Imperial Coll Sci Technol & Med, Dept Comp, London, England

关键词: 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;   

DOI  :  10.1016/j.neurobiolaging.2011.12.017

来源: Elsevier

【 摘 要 】

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. (c) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free