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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
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 .
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.ORCID iD: 0000-0001-6863-6679
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 .
Number of Authors: 512017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 56, no 2, p. 543-555Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
IOS Press, 2017. Vol. 56, no 2, p. 543-555
Keywords [en]
Alzheimer’s disease, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau protein
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-74045DOI: 10.3233/JAD-160668ISI: 000395077200011PubMedID: 28059783Scopus ID: 2-s2.0-85011320275OAI: oai:DiVA.org:oru-74045DiVA, id: diva2:1313954
Note

Funding Agencies:

Aegis of JPND  

Netherlands Organisation for Health Research and Development (ZonMw), the Netherlands  

Instituto de Salud Carlos III (ISCIII), Spain  PI11/3035  PI11/02425  PI14/01126 

Italian Ministry of Health, Italy  IG-2014-2354450 

Health Research Council of the Academy of Finland, Finland  263193 

TUBITAK, Turkey  112S360 

Fundacaopara a Ciencia e a Tecnologia (FCT), Portugal  PIC/IC/83206/2007  JPND/0005/2011 

ZonMW  

CAVIA project to Verbeek  733050202 

Alzheimer Nederland  

Alzheimer's drug discovery foundation  

ISAO  

CIBERNED program (Program 1, Alzheimer Disease)  

FondoEuropeo de Desarrollo Regional (FEDER)  

Union Europea  

Marato TV3  201412.10 

Alzheimer's Association  

IMI Project "PharmaCog", FP7  

AXA Research Fund  

Fondation Universite Pierre et Marie Curie  

Fondation pour la Recherche sur Alzheimer, Paris, France  

Ce travail a beneficie d'une aide de l'Etat, program "Investissements d'avenir"  ANR-10-IAIHU-06 

Swiss National Science Foundation  

Dutch national 'Deltaplan for Dementia'  

Una manera de hacer Europa 

Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-18Bibliographically approved

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Freund-Levi, Yvonne

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