TY - JOUR
T1 - Computer-assisted prediction of clinical progression in the earliest stages of AD
AU - Rhodius-Meester, Hanneke F.M.
AU - Liedes, Hilkka
AU - Koikkalainen, Juha
AU - Wolfsgruber, Steffen
AU - Coll-Padros, Nina
AU - Kornhuber, Johannes
AU - Peters, Oliver
AU - Jessen, Frank
AU - Kleineidam, Luca
AU - Molinuevo, José Luis
AU - Rami, Lorena
AU - Teunissen, Charlotte E.
AU - Barkhof, Frederik
AU - Sikkes, Sietske A.M.
AU - Wesselman, Linda M.P.
AU - Slot, Rosalinde E.R.
AU - Verfaillie, Sander C.J.
AU - Scheltens, Philip
AU - Tijms, Betty M.
AU - Lötjönen, Jyrki
AU - van der Flier, Wiesje M.
N1 - Funding Information:
Research of the VUmc Alzheimer Center is part of the neurodegeneration research program of the Amsterdam Neuroscience. The VUmc Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc Fonds . The clinical database structure was developed with funding from Stichting Dioraphte . For the development of the PredictAD tool, the 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 Euro-SCD project has been funded by the EU Joint Program–Neurodegenerative Disease Research ( JPND_PS_FP-689-019 ). DCN has been funded by a grant from the German Federal Ministry of Education and Research (BMBF): Kompetenznetz Demenzen ( 01GI0420 ). Hanneke FM Rhodius-Meester is appointed on PredictND, a grant from the European Seventh Framework Program project PredictND under grant agreement 611005. Frederik Barkhof is supported by the NIHR UCLH Biomedical Research Center. Sietske AM Sikkes is supported by an Off Road grant ( ZonMw #451001010 ). Wiesje M. van der Flier is a recipient of a research grant from Gieskes-Strijbis Fonds . Betty M. Tijms receives grant support from ZonMw ( #73305056 and #733050824 ).
Funding Information:
Author disclosures: Hanneke F.M. Rhodius-Meester, Hilkka Liedes, Steffen Wolfsgruber, Nina Coll-Padros, Johannes Kornhuber, Luca Kleineidam, Lorena Rami, Sietske A. Sikkes, Linda MP Wesselman, Rosalinde E.R. Slot, Sander C.J. Verfaillie, and Betty Tijms report no disclosures. Juha Koikkalainen and Jyrki Lötjönen all report that the VTT Technical Research Center of Finland owns the following IPR related to the article: (1) J. Koikkalainen and J. Lotjonen—a method for inferring the state of a system, US7,840,510 B2, PCT/FI2007/050277; and (2) J. Lotjonen, J. Koikkalainen, and J. Mattila—state inference in a heterogeneous system, PCT/FI2010/050545, FI20125177. Juha Koikkalainen and Jyrki Lötjönen are shareholders in Combinostics Oy. Oliver Peters has received speaker honoraria from Eli Lilly & Company, Novartis, Affiris, and Roche and has received research support from Axon , Axovant , Biogen , Eli Lilly and Company , Lundbeck , Pharmatrophix , Probiodrug , Novartis , Roche , Janssen , Piramal , Takeda , and TRX Pharmaceuticals . Frank Jessen has received fees for advisory boards of Eli Lilly, Biogene, MSD, Janssen Cilag, Roche, AC Immune, and Novartis. José Luis Molinuevo is the PI of trials funded by Roche , Merck , Novartis , and Janssen and has received speaker or consultant fees from Roche, Roche diagnostics, Biogen, Merck, Novartis, Oryzon, IBL, Axovant, Lundbeck, and Lilly. Charlotte E. Teunissen is a member of the Innogenetics International Advisory Boards of Fujirebio/Innogenetics and Roche. Frederik Barkhof serves/has served on the advisory boards of Bayer-Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA, Merck-Serono, Novartis, Roche, Synthon BV, Jansen Research, and Genzyme. He received funding from the Dutch MS Society and EU-FP7 and has been a speaker at symposia organized by the Serono Symposia Foundation and Medscape. Philip Scheltens has served as a consultant for Wyeth-Elan, Genentech, Danone, and Novartis and received funding for travel from Pfizer , Elan , Janssen , and Danone Research . Wiesje M. van der Flier performs contract research for Biogen. Research programs of Wiesje M. van der Flier have been funded by ZonMw , NWO , EU-FP7 , Alzheimer Nederland , CardioVascular Onderzoek Nederland , Stichting Dioraphte , Gieskes-Strijbis Fonds , Boehringer Ingelheim , Piramal Neuroimaging , Combinostics , Roche BV , and Janssen Stellar . She has been an invited speaker at Boehringer Ingelheim and Biogen. All funding is paid to her institution.
Publisher Copyright:
© 2018 The Authors
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/1
Y1 - 2018/1
N2 - Introduction: Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. Methods: We included 674 patients with SCD (46% female, 64 ± 9 years, Mini–Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. Results: After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). Discussion: We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.
AB - Introduction: Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. Methods: We included 674 patients with SCD (46% female, 64 ± 9 years, Mini–Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. Results: After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). Discussion: We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.
KW - Alzheimer's disease
KW - Clinical decision support system
KW - Diagnostic test assessment
KW - Prognosis
KW - Subjective cognitive decline
UR - http://www.scopus.com/inward/record.url?scp=85056565151&partnerID=8YFLogxK
U2 - 10.1016/j.dadm.2018.09.001
DO - 10.1016/j.dadm.2018.09.001
M3 - Article
C2 - 30619929
AN - SCOPUS:85056565151
VL - 10
SP - 726
EP - 736
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
SN - 2352-8729
ER -