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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/19148

Title: Correcting for the Absence of a Gold Standard Improves Diagnostic Accuracy of Biomarkers in Alzheimer's Disease
Authors: Coart, Els
GARCIA BARRADO, Leandro
Duits, Flora H.
Scheltens, Philip
van der Flier, Wiesje M.
Teunissen, Charlotte E.
van der Vies, Saskia M.
BURZYKOWSKI, Tomasz
Issue Date: 2015
Publisher: IOS PRESS
Citation: JOURNAL OF ALZHEIMERS DISEASE, 46 (4), p. 889-899
Abstract: Background: Studies investigating the diagnostic accuracy of biomarkers for Alzheimer's disease (AD) are typically performed using the clinical diagnosis or amyloid-beta positron emission tomography as the reference test. However, neither can be considered a gold standard or a perfect reference test for AD. Not accounting for errors in the reference test is known to cause bias in the diagnostic accuracy of biomarkers. Objective: To determine the diagnostic accuracy of AD biomarkers while taking the imperfectness of the reference test into account. Methods: To determine the diagnostic accuracy of AD biomarkers and taking the imperfectness of the reference test into account, we have developed a Bayesian method. This method establishes the biomarkers' true value in predicting the AD-pathology status by combining the reference test and the biomarker data with available information on the reliability of the reference test. The new methodology was applied to two clinical datasets to establish the joint accuracy of three cerebrospinal fluid biomarkers (amyloid-beta(1-42), Total tau, and P-tau(181p)) by including the clinical diagnosis as imperfect reference test into the analysis. Results: The area under the receiver-operating-characteristics curve to discriminate between AD and controls, increases from 0.949 (with 95% credible interval [0.935,0.960]) to 0.990 ([0.985,0.995]) and from 0.870 ([0.817,0.912]) to 0.975 ([0.943,0.990]) for the cohorts, respectively. Conclusions: Use of the Bayesian methodology enables an improved estimate of the exact diagnostic value of AD biomarkers and overcomes the lack of a gold standard for AD. Using the new method will increase the diagnostic confidence for early stages of AD.
Notes: [Coart, Els; Burzykowski, Tomasz] IDDI, B-1340 Louvain La Neuve, Belgium. [Barrado, Leandro Garcia; Burzykowski, Tomasz] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat I BioSt, Diepenbeek, Belgium. [Duits, Flora H.; Scheltens, Philip; van der Flier, Wiesje M.] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. [Duits, Flora H.; Scheltens, Philip; van der Flier, Wiesje M.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands. [van der Flier, Wiesje M.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Teunissen, Charlotte E.] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Neurochem Lab & Biobank, Amsterdam, Netherlands. [van der Vies, Saskia M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
URI: http://hdl.handle.net/1942/19148
DOI: 10.3233/JAD-142886
ISI #: 000357429300008
ISSN: 1387-2877
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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