Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

Research output: Contribution to journalArticle

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.

Details

Authors
  • Linda J C van Waalwijk van Doorn
  • Juan D. Gispert
  • H. Bea Kuiperij
  • Jurgen A H R Claassen
  • Andrea Arighi
  • Inês Baldeiras
  • Kaj Blennow
  • Marco Bozzali
  • Miguel Castelo-Branco
  • Enrica Cavedo
  • Derya D. Emek-Savaş
  • Erden Eren
  • Paolo Eusebi
  • Lucia Farotti
  • Chiara Fenoglio
  • Juan Fortea Ormaechea
  • Yvonne Freund-Levi
  • Giovanni B Frisoni
  • Daniela Galimberti
  • Sermin Genc
  • Viviana Greco
  • Harald Hampel
  • Sanna-Kaisa Herukka
  • Yawu Liu
  • Albert Lladó
  • Alberto Lleó
  • Flavio M. Nobili
  • Kader K. Oguz
  • Lucilla Parnetti
  • João Pereira
  • Agnese Picco
  • Maria Pikkarainen
  • Catarina Resende De Oliveira
  • Esen Saka
  • Nicola Salvadori
  • Raquel Sanchez-Valle
  • Isabel Santana
  • Elio Scarpini
  • Philip Scheltens
  • Hilkka Soininen
  • Roberto Tarducci
  • Charlotte Teunissen
  • Magda Tsolaki
  • Andrea Urbani
  • Eduard Vilaplana
  • Pieter Jelle Visser
  • Görsev Yener
  • José L Molinuevo
  • Olga Meulenbroek
  • Marcel Verbeek
Organisations
External organisations
  • Radboud University Nijmegen
  • Pompeu Fabra University
  • University Hospital of Coimbra
  • Sahlgrenska University Hospital
  • Paris-Sorbonne University
  • University of Milan
  • IRCCS Fondazione Santa Lucia
  • University of Coimbra
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Alzheimer's disease, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau protein
Original languageEnglish
Pages (from-to)543-555
Number of pages13
JournalJournal of Alzheimer's Disease
Volume56
Issue number2
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes