@article{9043ccc8a7c54c7484fa197d04ba8da2,
title = "Decision tree supports the interpretation of CSF biomarkers in Alzheimer's disease",
abstract = "Introduction: We developed and validated a clinically applicable decision tree for the use of cerebrospinal fluid biomarkers in the diagnosis of Alzheimer's disease (AD).Methods: Subjects with probable AD (n = 1004) and controls (n = 442) were included. A decision tree was modeled using Classification And Regression Tree analysis in a training cohort (AD n = 221; controls n = 221) and validated in an independent cohort (AD n = 783; controls n = 221). Diagnostic performance was compared to previously defined cutoffs (amyloid beta 1-42 < 813 pg/ml; tau>375 pg/ml).Results: Two cerebrospinal fluid AD biomarker profiles were revealed: the {"}classical{"} AD biomarker profile (amyloid beta 1-42: 647-803 pg/ml; tau >374 pg/ml) and an {"}atypical{"} AD biomarker profile with strongly decreased amyloid beta 1-42 (<647 pg/ml) and normal tau concentrations (<374 pg/ml). Compared to previous cutoffs, the decision tree performed better on diagnostic accuracy (86\% [84-88] vs 80\% [78-83]).Discussion: Two cerebrospinal fluid AD biomarker profiles were identified and incorporated in a readily applicable decision tree, which improved diagnostic accuracy. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.",
keywords = "Alzheimer's disease, CSF, Amyloid beta 1-42, Tau, Clinical implementation, Decision tree, CART, Cutoff, Cerebrospinal fluid",
author = "R.B. Mofrad and N.S.M. Schoonenboom and B.M. Tijms and P. Scheltens and P.J. Visser and \{van der Flier\}, W.M. and C.E. Teunissen",
note = "Funding Information: Disclosures: RBM and NSMS had no disclosures to report. BMT received grant funding from the ZonMW Memorabel grant program \#73305056 and \#733050824. PS has acquired grant support (for the institution) from Piramal. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen and Roche (diagnostics). He is PI of studies with Probiodrug and EIP Pharma. PJV serves as an advisory board member of Eli-Lilly, is consultant for Janssen, and has received grants from GE healthcare and Biogen. Research programs of WMVDF have been funded by ZonMW, NWO, EU-FP7, Alzheimer Nederland, CardioVasculair Onderzoek Nederland, Stichting Dioraphte, Gieskes-Strijbis fonds, Biogen MA Inc, Boehringer Ingelheim, Piramal Neuroimaging, Roche BV, Janssen Stellar, Combinostics. WMVDF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. WMVDF has been an invited speaker at Boehringer Ingelheim and Biogen MA Inc. All funding is paid to her institution. CET received grant funding from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation, Alzheimer Netherlands. CET has functioned in advisory boards of Fujirebio and Roche received nonfinancial support in the form of research consumables from ADx Neurosciences and Euroimmun, performed contract research or received grants from Probiodrug, Janssen prevention center, Boehringer, Brains online, Axon Neurosciences, EIP pharma, Roche. These funding sources had no influence on study analyses or article writing. Funding Information: Research of the VUmc Alzheimer center is part of the neurodegeneration research program of the Neuroscience Amsterdam. The VUmc Alzheimer Center is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte . Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2019",
month = dec,
day = "1",
doi = "10.1016/j.dadm.2018.10.004",
language = "English",
volume = "11",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",
number = "1",
}