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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 (author)
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands
Gispert, Juan D. (author)
Pompeu Fabra University
Kuiperij, H. Bea (author)
Radboud University Nijmegen
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Claassen, Jurgen A H R (author)
Radboud University Nijmegen,University of Milan
Arighi, Andrea (author)
University of Milan
Baldeiras, Inês (author)
University Hospital of Coimbra
Blennow, Kaj (author)
Sahlgrenska University Hospital
Bozzali, Marco (author)
IRCCS Fondazione Santa Lucia
Castelo-Branco, Miguel (author)
University of Coimbra
Cavedo, Enrica (author)
Paris-Sorbonne University
Emek-Savaş, Derya D. (author)
Eren, Erden (author)
Eusebi, Paolo (author)
Farotti, Lucia (author)
Fenoglio, Chiara (author)
Ormaechea, Juan Fortea (author)
Freund-Levi, Yvonne, 1956- (author)
Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
Frisoni, Giovanni B (author)
Galimberti, Daniela (author)
Genc, Sermin (author)
Greco, Viviana (author)
Hampel, Harald (author)
Herukka, Sanna-Kaisa (author)
Liu, Yawu (author)
Lladó, Albert (author)
Lleó, Alberto (author)
Nobili, Flavio M. (author)
Oguz, Kader K. (author)
Parnetti, Lucilla (author)
Pereira, João (author)
Picco, Agnese (author)
Pikkarainen, Maria (author)
De Oliveira, Catarina Resende (author)
Saka, Esen (author)
Salvadori, Nicola (author)
Sanchez-Valle, Raquel (author)
Santana, Isabel (author)
Scarpini, Elio (author)
Scheltens, Philip (author)
Soininen, Hilkka (author)
Tarducci, Roberto (author)
Teunissen, Charlotte (author)
Tsolaki, Magda (author)
Urbani, Andrea (author)
Vilaplana, Eduard (author)
Visser, Pieter Jelle (author)
Wallin, Asa K. (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
Yener, Görsev (author)
Molinuevo, José L (author)
Meulenbroek, Olga (author)
Verbeek, Marcel (author)
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands
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 (creator_code:org_t)
IOS Press, 2017
2017
English 13 s.
In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

Alzheimer's disease
amyloid biomarkers
cerebrospinal fluid
lateral ventricles
tau protein
Alzheimer’s disease

Publication and Content Type

art (subject category)
ref (subject category)

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