TY - JOUR
T1 - Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
AU - van Doorn, Linda J. C. van Waalwijk
AU - Gispert, Juan D.
AU - Kuiperij, H. Bea
AU - Claassen, Jurgen A. H. R.
AU - Arighi, Andrea
AU - Baldeiras, Ines
AU - Blennow, Kaj
AU - Bozzali, Marco
AU - Castelo-Branco, Miguel
AU - Cavedo, Enrica
AU - Emek-Savas, Derya D.
AU - Eren, Erden
AU - Eusebi, Paolo
AU - Farotti, Lucia
AU - Fenoglio, Chiara
AU - Ormaechea, Juan Fortea
AU - Freund-Levi, Yvonne
AU - Frisoni, Giovanni B.
AU - Galimberti, Daniela
AU - Genc, Sermin
AU - Greco, Viviana
AU - Hampel, Harald
AU - Herukka, Sanna-Kaisa
AU - Liu, Yawu
AU - Llado, Albert
AU - Lleo, Alberto
AU - Nobili, Flavio M.
AU - Oguz, Kader K.
AU - Parnetti, Lucilla
AU - Pereira, Joao
AU - Picco, Agnese
AU - Pikkarainen, Maria
AU - de Oliveira, Catarina Resende
AU - Saka, Esen
AU - Salvadori, Nicola
AU - Sanchez-Valle, Raquel
AU - Santana, Isabel
AU - Scarpini, Elio
AU - Scheltens, Philip
AU - Soininen, Hilkka
AU - Tarducci, Roberto
AU - Teunissen, Charlotte
AU - Tsolaki, Magda
AU - Urbani, Andrea
AU - Vilaplana, Eduard
AU - Visser, Pieter Jelle
AU - Wallin, Asa K.
AU - Yener, Gorsev
AU - Molinuevo, Jose L.
AU - Meulenbroek, Olga
AU - Verbeek, Marcel M.
PY - 2017
Y1 - 2017
N2 - 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., A beta(42), 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 A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): 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 A beta(42) 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 A beta(42) levels.
AB - 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., A beta(42), 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 A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): 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 A beta(42) 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 A beta(42) levels.
KW - Alzheimer's disease
KW - amyloid biomarkers
KW - cerebrospinal fluid
KW - lateral ventricles
KW - tau protein
KW - MILD COGNITIVE IMPAIRMENT
KW - AD-CSF-INDEX
KW - NATIONAL INSTITUTE
KW - ASSOCIATION WORKGROUPS
KW - DIAGNOSTIC GUIDELINES
KW - BRAIN ATROPHY
KW - BIOMARKERS
KW - DEMENTIA
KW - RECOMMENDATIONS
KW - TAU
U2 - 10.3233/JAD-160668
DO - 10.3233/JAD-160668
M3 - Article
C2 - 28059783
SN - 1387-2877
VL - 56
SP - 543
EP - 555
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -