TY - JOUR
T1 - Selection of memory clinic patients for CSF biomarker assessment can be restricted to a quarter of cases by using computerized decision support, without compromising diagnostic accuracy
AU - Rhodius-Meester, Hanneke F.M.
AU - van Maurik, Ingrid S.
AU - Koikkalainen, Juha
AU - Tolonen, Antti
AU - Frederiksen, Kristian S.
AU - Hasselbalch, Steen G.
AU - Soininen, Hilkka
AU - Herukka, Sanna Kaisa
AU - Remes, Anne M.
AU - Teunissen, Charlotte E.
AU - Barkhof, Frederik
AU - Pijnenburg, Yolande A.L.
AU - Scheltens, Philip
AU - Lötjönen, Jyrki
AU - van der Flier, Wiesje M.
N1 - Funding Information:
This study is partly funded by Combinostics. The funder provided support in the form of salaries for authors [JK and JL], and had an additional role in the study as Juha Koikkalainen and Jyrki L?tj?nen developed the method and quantitative raw data were generated using Combinostics? tools. They also reviewed the manuscript. The specific roles of these authors are articulated in the ?author contributions? section. For development of the PredictAD tool, VTT Technical Research Centre of Finland has received funding from European Union?s Seventh Framework Programme for research, technological development and demonstration under grant agreements 601055 (VPH-DARE@IT), 224328 (PredictAD), and 611005 (PredictND). The latter had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.? Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Wiesje M van der Flier holds the Pasman chair.
Publisher Copyright:
© 2020 Rhodius-Meester et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - INTRODUCTION: An accurate and timely diagnosis for Alzheimer's disease (AD) is important, both for care and research. The current diagnostic criteria allow the use of CSF biomarkers to provide pathophysiological support for the diagnosis of AD. How these criteria should be operationalized by clinicians is unclear. Tools that guide in selecting patients in which CSF biomarkers have clinical utility are needed. We evaluated computerized decision support to select patients for CSF biomarker determination. METHODS: We included 535 subjects (139 controls, 286 Alzheimer's disease dementia, 82 frontotemporal dementia and 28 vascular dementia) from three clinical cohorts. Positive (AD like) and negative (normal) CSF biomarker profiles were simulated to estimate whether knowledge of CSF biomarkers would impact (confidence in) diagnosis. We applied these simulated CSF values and combined them with demographic, neuropsychology and MRI data to initiate CSF testing (computerized decision support approach). We compared proportion of CSF measurements and patients diagnosed with sufficient confidence (probability of correct class ≥0.80) based on an algorithm with scenarios without CSF (only neuropsychology, MRI and APOE), CSF according to the appropriate use criteria (AUC) and CSF for all patients. RESULTS: The computerized decision support approach recommended CSF testing in 140 (26%) patients, which yielded a diagnosis with sufficient confidence in 379 (71%) of all patients. This approach was more efficient than CSF in none (0% CSF, 308 (58%) diagnosed), CSF selected based on AUC (295 (55%) CSF, 350 (65%) diagnosed) or CSF in all (100% CSF, 348 (65%) diagnosed). CONCLUSIONS: We used a computerized decision support with simulated CSF results in controls and patients with different types of dementia. This approach can support clinicians in making a balanced decision in ordering additional biomarker testing. Computer-supported prediction restricts CSF testing to only 26% of cases, without compromising diagnostic accuracy.
AB - INTRODUCTION: An accurate and timely diagnosis for Alzheimer's disease (AD) is important, both for care and research. The current diagnostic criteria allow the use of CSF biomarkers to provide pathophysiological support for the diagnosis of AD. How these criteria should be operationalized by clinicians is unclear. Tools that guide in selecting patients in which CSF biomarkers have clinical utility are needed. We evaluated computerized decision support to select patients for CSF biomarker determination. METHODS: We included 535 subjects (139 controls, 286 Alzheimer's disease dementia, 82 frontotemporal dementia and 28 vascular dementia) from three clinical cohorts. Positive (AD like) and negative (normal) CSF biomarker profiles were simulated to estimate whether knowledge of CSF biomarkers would impact (confidence in) diagnosis. We applied these simulated CSF values and combined them with demographic, neuropsychology and MRI data to initiate CSF testing (computerized decision support approach). We compared proportion of CSF measurements and patients diagnosed with sufficient confidence (probability of correct class ≥0.80) based on an algorithm with scenarios without CSF (only neuropsychology, MRI and APOE), CSF according to the appropriate use criteria (AUC) and CSF for all patients. RESULTS: The computerized decision support approach recommended CSF testing in 140 (26%) patients, which yielded a diagnosis with sufficient confidence in 379 (71%) of all patients. This approach was more efficient than CSF in none (0% CSF, 308 (58%) diagnosed), CSF selected based on AUC (295 (55%) CSF, 350 (65%) diagnosed) or CSF in all (100% CSF, 348 (65%) diagnosed). CONCLUSIONS: We used a computerized decision support with simulated CSF results in controls and patients with different types of dementia. This approach can support clinicians in making a balanced decision in ordering additional biomarker testing. Computer-supported prediction restricts CSF testing to only 26% of cases, without compromising diagnostic accuracy.
KW - Aged
KW - Alzheimer Disease/cerebrospinal fluid
KW - Biomarkers/cerebrospinal fluid
KW - Decision Support Systems, Clinical
KW - Female
KW - Humans
KW - Male
KW - Memory
KW - Middle Aged
KW - Patient Selection
KW - Sensitivity and Specificity
UR - http://www.scopus.com/inward/record.url?scp=85077941773&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0226784
DO - 10.1371/journal.pone.0226784
M3 - Article
C2 - 31940390
AN - SCOPUS:85077941773
SN - 1932-6203
VL - 15
SP - e0226784
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0226784
ER -