@article{59cf59392ff74b6aaed9dd07dfb61a9a,
title = "Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes",
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.",
keywords = "Aged, Algorithms, Alzheimer Disease, Alzheimer's disease, Amyloid beta-Peptides, Area Under Curve, Atrophy, Biomarkers, Cerebral Ventricles, Cognitive Dysfunction, Female, Hippocampus, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pattern Recognition, Automated, Peptide Fragments, ROC Curve, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau Proteins, tau protein, Aged, Algorithms, Alzheimer Disease, Alzheimer's disease, Amyloid beta-Peptides, Area Under Curve, Atrophy, Biomarkers, Cerebral Ventricles, Cognitive Dysfunction, Female, Hippocampus, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pattern Recognition, Automated, Peptide Fragments, ROC Curve, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau Proteins, tau protein",
author = "{Van Waalwijk Van Doorn}, {Linda J.C.} and Gispert, {Juan D.} and Kuiperij, {H. Bea} and Claassen, {Jurgen A.H.R.} and Andrea Arighi and In{\^e}s Baldeiras and Kaj Blennow and Marco Bozzali and Miguel Castelo-Branco and Enrica Cavedo and Emek-Sava{\c s}, {Derya D.} and Erden Eren and Paolo Eusebi and Lucia Farotti and Chiara Fenoglio and Ormaechea, {Juan Fortea} and Yvonne Freund-Levi and Frisoni, {Giovanni B.} and Daniela Galimberti and Sermin Genc and Viviana Greco and Harald Hampel and Sanna-Kaisa Herukka and Yawu Liu and Albert Llad{\'o} and Alberto Lle{\'o} and Nobili, {Flavio M.} and Oguz, {Kader K.} and Lucilla Parnetti and Jo{\~a}o Pereira and Agnese Picco and Maria Pikkarainen and {De Oliveira}, {Catarina Resende} and Esen Saka and Nicola Salvadori and Raquel Sanchez-Valle and Isabel Santana and Elio Scarpini and Philip Scheltens and Hilkka Soininen and Roberto Tarducci and Charlotte Teunissen and Magda Tsolaki and Andrea Urbani and Eduard Vilaplana and Visser, {Pieter Jelle} and Wallin, {Asa K.} and G{\"o}rsev Yener and Molinuevo, {Jos{\'e} L.} and Olga Meulenbroek and Verbeek, {Marcel M.}",
year = "2017",
doi = "10.3233/JAD-160668",
language = "English",
volume = "56",
pages = "543--555",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press BV",
}