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

van Waalwijk van Doorn, Linda J C; Gispert, Juan D.; Kuiperij, H. Bea; Claassen, Jurgen A H R; Arighi, Andrea; Baldeiras, Inês; Blennow, Kaj; Bozzali, Marco; Castelo-Branco, Miguel and Cavedo, Enrica, et al. (2017) In Journal of Alzheimer's Disease 56(2). p.543-555
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... (More)

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.

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publication status
published
subject
keywords
Alzheimer's disease, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau protein
in
Journal of Alzheimer's Disease
volume
56
issue
2
pages
13 pages
publisher
IOS Press
external identifiers
  • scopus:85011320275
  • wos:000395077200011
ISSN
1387-2877
DOI
10.3233/JAD-160668
language
English
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yes
id
b541c926-4f61-4333-a562-f7ff4e8feb6b
date added to LUP
2017-02-16 14:12:09
date last changed
2018-01-28 04:27:42
@article{b541c926-4f61-4333-a562-f7ff4e8feb6b,
  abstract     = {<p>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., Aβ<sub>42</sub>, 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 Aβ<sub>42</sub> levels inversely correlated to VV/TIV in the whole study population (Aβ<sub>42</sub>: r=-0.28; p&lt;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&lt;0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aβ<sub>42</sub> 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 Aβ<sub>42</sub> levels.</p>},
  author       = {van Waalwijk van Doorn, Linda J C and Gispert, Juan D. and Kuiperij, H. Bea and Claassen, Jurgen A H R and Arighi, Andrea and Baldeiras, Inês and Blennow, Kaj and Bozzali, Marco and Castelo-Branco, Miguel and Cavedo, Enrica and Emek-Savaş, Derya D. and Eren, Erden and Eusebi, Paolo and Farotti, Lucia and Fenoglio, Chiara and Ormaechea, Juan Fortea and Freund-Levi, Yvonne and Frisoni, Giovanni B and Galimberti, Daniela and Genc, Sermin and Greco, Viviana and Hampel, Harald and Herukka, Sanna-Kaisa and Liu, Yawu and Lladó, Albert and Lleó, Alberto and Nobili, Flavio M. and Oguz, Kader K. and Parnetti, Lucilla and Pereira, João and Picco, Agnese and Pikkarainen, Maria and De Oliveira, Catarina Resende and Saka, Esen and Salvadori, Nicola and Sanchez-Valle, Raquel and Santana, Isabel and Scarpini, Elio and Scheltens, Philip and Soininen, Hilkka and Tarducci, Roberto and Teunissen, Charlotte and Tsolaki, Magda and Urbani, Andrea and Vilaplana, Eduard and Visser, Pieter Jelle and Wallin, Asa K. and Yener, Görsev and Molinuevo, José L and Meulenbroek, Olga and Verbeek, Marcel},
  issn         = {1387-2877},
  keyword      = {Alzheimer's disease,amyloid biomarkers,cerebrospinal fluid,lateral ventricles,tau protein},
  language     = {eng},
  number       = {2},
  pages        = {543--555},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes},
  url          = {http://dx.doi.org/10.3233/JAD-160668},
  volume       = {56},
  year         = {2017},
}