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.

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

Bozzali M;
2017-01-01

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., 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.
2017
56
2
543
555
van Doorn LJCV; Gispert JD; Kuiperij HB; Claassen JAHR; Arighi A; Baldeiras I; Blennow K; Bozzali M; Castelo-Branco M; Cavedo E; Emek-Savas 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 YW; Llado A; Lleo 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; Verbeek MM
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1765320
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