1. Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes.
- Author
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van Waalwijk van Doorn LJ, Gispert JD, Kuiperij HB, Claassen JA, Arighi A, Baldeiras I, Blennow K, Bozzali M, Castelo-Branco M, Cavedo E, Emek-Savaş DD, Eren E, Eusebi P, Farotti L, Fenoglio C, Ormaechea JF, Freund-Levi Y, Frisoni GB, Galimberti D, Genc S, Greco V, Hampel H, Herukka SK, Liu Y, Lladó A, Lleó A, Nobili FM, Oguz KK, Parnetti L, Pereira J, Picco A, Pikkarainen M, de Oliveira CR, Saka E, Salvadori N, Sanchez-Valle R, Santana I, Scarpini E, Scheltens P, Soininen H, Tarducci R, Teunissen C, Tsolaki M, Urbani A, Vilaplana E, Visser PJ, Wallin AK, Yener G, Molinuevo JL, Meulenbroek O, and Verbeek MM
- Subjects
- Aged, Algorithms, Amyloid beta-Peptides cerebrospinal fluid, Area Under Curve, Atrophy, Biomarkers cerebrospinal fluid, Female, Hippocampus diagnostic imaging, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pattern Recognition, Automated, Peptide Fragments cerebrospinal fluid, ROC Curve, tau Proteins cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnostic imaging, Cerebral Ventricles diagnostic imaging, Cognitive Dysfunction cerebrospinal fluid, Cognitive Dysfunction diagnostic imaging
- Abstract
Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aβ42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Aβ42 levels inversely correlated to VV/TIV in the whole study population (Aβ42: r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aβ42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Aβ42 levels.
- Published
- 2017
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