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Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study

2019-11Journal article Restricted access
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dc.contributor.authorvan Maurik, Ingrid S.
dc.contributor.authorVos, Stephanie J.
dc.contributor.authorBos, Isabelle
dc.contributor.authorBouwman, Femke H.
dc.contributor.authorTeunissen, Charlotte E.
dc.contributor.authorScheitens, Philip
dc.contributor.authorBarkhof, Frederik
dc.contributor.authorFrolich, Lutz
dc.contributor.authorKornhuber, Johannes
dc.contributor.authorWiftfang, Jens
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorPeters, Oliver
dc.contributor.authorROther, Eckart
dc.contributor.authorNobili, Flavio
dc.contributor.authorFrisoni, Giovanni B.
dc.contributor.authorSpiru, Luiza
dc.contributor.authorFreund-Levi, Yvonne
dc.contributor.authorWallin, Asa K.
dc.contributor.authorHampel, Harald
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorTsolaki, Magda
dc.contributor.authorVerhey, Frans
dc.contributor.authorKloszewska, Iwona
dc.contributor.authorMecocci, Patrizia
dc.contributor.authorVellas, Bruno
dc.contributor.authorLovestone, Simon
dc.contributor.authorGailuzzi, Samantha
dc.contributor.authorHerukka, Sanna-Kaisa
dc.contributor.authorSantana, Isabel
dc.contributor.authorBaldeiras, Ines
dc.contributor.authorde Mendonca, Alexandre
dc.contributor.authorSilva, Dina
dc.contributor.authorChetelat, Gael
dc.contributor.authorEgret, Stephanie
dc.contributor.authorPalmqvist, Sebastian
dc.contributor.authorHansson, Oskar
dc.contributor.authorVisser, Pieter Jelle
dc.contributor.authorBerkhof, Johannes
dc.contributor.authorvan der Flier, Wiesje M.
dc.date.accessioned2020-07-24T10:51:07Z
dc.date.available2020-07-24T10:51:07Z
dc.date.issued2019-11
dc.description.abstractBackground Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer’s Disease (EMIF-AD; n=883), Alzheimer’s Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models—a demographics model, a hippocampal volume model, and a CSF biomarkers model—by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell’s C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer’s Association research framework. Findings We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell’s C 0·62, 95% CI 0·59–0·65), validated hippocampal volume model (0·67, 0·62–0·72), and updated CSF biomarkers model (0·72, 0·68–0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71–0·76). Interpretation We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer’s disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants’ understanding, emotional wellbeing, and behaviour. Funding ZonMW-Memorabel.
dc.description.sponsorshipStichting Alzheimer Nederland
dc.description.sponsorshipStichting VUmc Fonds
dc.description.sponsorshipJoint Program-Neurodegenerative Disease Research [733051083, WMvdF]
dc.description.sponsorshipZonMW-Memorabel (ABIDE) [733050201]
dc.description.sponsorshipNIHR Biomedical Research Centre at University College London Hospital
dc.description.sponsorshipAXA Research Fund
dc.description.sponsorshipFondation partenariale Sorbonne Universite
dc.description.sponsorshipFondation pour la Recherche sur Alzheimer, Paris, France [ANR-10-AIHU-06]
dc.description.sponsorshipFrench program (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) - ADNI (National Institutes of Health)French National Research Agency (ANR) [U01 AG024904]
dc.description.sponsorshipDepartment of Defense ADNIUnited States Department of Defense [W81XWH-12-2-0012]
dc.description.sponsorshipNational Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA)
dc.description.sponsorshipNational Institute of Biomedical Imaging and BioengineeringUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
dc.description.sponsorshipAlzheimer's AssociationAlzheimer's Association
dc.description.sponsorshipAlzheimer's Drug Discovery Foundation
dc.description.sponsorshipAraclon Biotech
dc.description.sponsorshipCogstate
dc.description.sponsorshipEisaiEisai Co Ltd
dc.description.sponsorshipElan Pharmaceuticals
dc.description.sponsorshipEuroImmun
dc.description.sponsorshipF Hoffmann-La Roche and its affiliated company Genentech
dc.description.sponsorshipFujirebio
dc.description.sponsorshipJohnson & Johnson Pharmaceutical Research & Development, Lumosity
dc.description.sponsorshipMeso Scale Diagnostics
dc.description.sponsorshipNovartis Pharmaceuticals CorporationNovartis
dc.description.sponsorshipCanadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR)
dc.description.sponsorshipADNI clinical sites in Canada
dc.description.sponsorship(Foundation for the National Institutes of Health)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA
dc.description.sponsorshipNorthern California Institute for Research and Education
dc.description.sponsorshipLaboratory for Neuro Imaging at the University of Southern California
dc.description.sponsorshipInnovative Medicines Initiative Joint Undertaking under EMIF [115372]
dc.description.sponsorshipEuropean Union - European CommissionEuropean Commission Joint Research CentreEuropean Union (EU) [QLRT-2001-2455]
dc.description.sponsorshipEuropean Regional Development Fund, through the Centro 2020 Regional Operational ProgrammeEuropean Union (EU) [CENTRO-01-0145-FEDER-000008:BrainHealth 2020]
dc.description.sponsorshipPortuguese national funds via FCT Fundacao para a Ciencia e a Tecnologia [POCI-01-0145FEDER-007440]
dc.description.sponsorshipAssociation Suisse pour la Recherche sur Alzheimer
dc.description.sponsorshipFondazione Agusta
dc.description.sponsorshipFondation VELUX
dc.description.sponsorshipSwiss National Science Foundation - Programme Hospitalier de Recherche Clinique (PHRCN) [2011-A01493-38, PHRCN 2012 12-006-0347]
dc.description.sponsorshipAgence Nationale de la RechercheFrench National Research Agency (ANR) [LONGVIE 2007]
dc.description.sponsorshipRegion Basse-Normandie and Fondation Plan Alzheimer (Alzheimer Plan)
dc.description.sponsorshipGerman Federal Ministry of Education and Research: Kompetenznetz Demenzen [01GI0420]
dc.description.sponsorshipEuropean Research CouncilEuropean Research Council (ERC)
dc.description.sponsorshipSwedish Research CouncilSwedish Research Council
dc.description.sponsorshipKnut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation
dc.description.sponsorshipMarianne and Marcus Wallenberg Foundation
dc.description.sponsorshipStrategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
dc.description.sponsorshipSwedish Alzheimer Foundation
dc.description.sponsorshipSwedish Brain Foundation
dc.description.sponsorshipParkinson Foundation of Sweden
dc.description.sponsorshipSkane University Hospital Foundation
dc.description.sponsorshipSwedish Federal Government
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/S1474-4422(19)30283-2
dc.identifier.issn1474-4422
dc.identifier.urihttp://hdl.handle.net/10400.1/14199
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.subjectAlzheimers disease
dc.subjectCsf biomarkers
dc.subjectDementia
dc.subjectProgression
dc.subjectDiagnosis
dc.titleBiomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1044
oaire.citation.issue11
oaire.citation.startPage1034
oaire.citation.titleLancet Neurology
oaire.citation.volume18
person.familyNameSilva
person.givenNameDina
person.identifier.orcid0000-0003-4437-2765
person.identifier.scopus-author-id26657734400
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationadb36ab3-1d97-48a3-b8df-544bef7c7aa0
relation.isAuthorOfPublication.latestForDiscoveryadb36ab3-1d97-48a3-b8df-544bef7c7aa0

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