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Prevalence of cerebral amyloid pathology in persons without dementia

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dc.contributor.authorJansen, Willemijn J.
dc.contributor.authorOssenkoppele, Rik
dc.contributor.authorKnol, Dirk L.
dc.contributor.authorTijms, Betty M.
dc.contributor.authorScheltens, Philip
dc.contributor.authorVerhey, Frans R. J.
dc.contributor.authorVisser, Pieter Jelle
dc.contributor.authorAalten, Pauline
dc.contributor.authorAarsland, Dag
dc.contributor.authorAlcolea, Daniel
dc.contributor.authorAlexander, Myriam
dc.contributor.authorRoe, Catherine M.
dc.contributor.authorRot, Uros
dc.contributor.authorRowe, Christopher C.
dc.contributor.authorRüther, Eckart
dc.contributor.authorSabri, Osama
dc.contributor.authorSanchez-Juan, Páscual
dc.contributor.authorSantana, Isabel
dc.contributor.authorSarazin, Marie
dc.contributor.authorSchröder, Johannes
dc.contributor.authorSchütte, Christin
dc.contributor.authorAlmdahl, Ina S.
dc.contributor.authorSeo, Sang W.
dc.contributor.authorSoetewey, Femke
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorSpiru, Luiza
dc.contributor.authorStruyfs, Hanne
dc.contributor.authorTeunissen, Charlotte E.
dc.contributor.authorTsolaki, Magda
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorVerbeek, Marcel M.
dc.contributor.authorVillemagne, Victor L.
dc.contributor.authorArnold, Steven E.
dc.contributor.authorVos, Stephanie J. B.
dc.contributor.authorvan Waalwijk van Doorn, Linda J. C.
dc.contributor.authorWaldemar, Gunhild
dc.contributor.authorWallin, Anders
dc.contributor.authorWallin, Åsa K.
dc.contributor.authorWiltfang, Jens
dc.contributor.authorWolk, David A.
dc.contributor.authorZboch, Marzena
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorBaldeiras, Inês
dc.contributor.authorBarthel, Henryk
dc.contributor.authorvan Berckel, Bart N. M.
dc.contributor.authorBibeau, Kristen
dc.contributor.authorBlennow, Kaj
dc.contributor.authorBrooks, David J.
dc.contributor.authorvan Buchem, Mark A.
dc.contributor.authorCamus, Vincent
dc.contributor.authorCavedo, Enrica
dc.contributor.authorChen, Kewei
dc.contributor.authorChetelat, Gael
dc.contributor.authorCohen, Ann D.
dc.contributor.authorDrzezga, Alexander
dc.contributor.authorEngelborghs, Sebastiaan
dc.contributor.authorFagan, Anne M.
dc.contributor.authorFladby, Tormod
dc.contributor.authorFleisher, Adam S.
dc.contributor.authorvan der Flier, Wiesje M.
dc.contributor.authorFord, Lisa
dc.contributor.authorFörster, Stefan
dc.contributor.authorFortea, Juan
dc.contributor.authorFoskett, Nadia
dc.contributor.authorFrederiksen, Kristian S.
dc.contributor.authorFreund-Levi, Yvonne
dc.contributor.authorFrisoni, Giovanni B.
dc.contributor.authorFroelich, Lutz
dc.contributor.authorGabryelewicz, Tomasz
dc.contributor.authorGill, Kiran Dip
dc.contributor.authorGkatzima, Olymbia
dc.contributor.authorGómez-Tortosa, Estrella
dc.contributor.authorGordon, Mark Forrest
dc.contributor.authorGrimmer, Timo
dc.contributor.authorHampel, Harald
dc.contributor.authorHausner, Lucrezia
dc.contributor.authorHellwig, Sabine
dc.contributor.authorHerukka, Sanna-Kaisa
dc.contributor.authorHildebrandt, Helmut
dc.contributor.authorIshihara, Lianna
dc.contributor.authorIvanoiu, Adrian
dc.contributor.authorJagust, William J.
dc.contributor.authorJohannsen, Peter
dc.contributor.authorKandimalla, Ramesh
dc.contributor.authorKapaki, Elisabeth
dc.contributor.authorKlimkowicz-Mrowiec, Aleksandra
dc.contributor.authorKlunk, William E.
dc.contributor.authorKöhler, Sebastian
dc.contributor.authorKoglin, Norman
dc.contributor.authorKornhuber, Johannes
dc.contributor.authorKramberger, Milica G.
dc.contributor.authorVan Laere, Koen
dc.contributor.authorLandau, Susan M.
dc.contributor.authorLee, Dong Young
dc.contributor.authorde Leon, Mony
dc.contributor.authorLisetti, Viviana
dc.contributor.authorLleó, Alberto
dc.contributor.authorMadsen, Karine
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorMarcusson, Jan
dc.contributor.authorMattsson, Niklas
dc.contributor.authorDe Mendonça, Alexandre
dc.contributor.authorMeulenbroek, Olga
dc.contributor.authorMeyer, Philipp T.
dc.contributor.authorMintun, Mark A.
dc.contributor.authorMok, Vincent
dc.contributor.authorMolinuevo, José Luis
dc.contributor.authorMøllergård, Hanne M.
dc.contributor.authorMorris, John C.
dc.contributor.authorMroczko, Barbara
dc.contributor.authorVan der Mussele, Stefan
dc.contributor.authorNa, Duk L.
dc.contributor.authorNewberg, Andrew
dc.contributor.authorNordberg, Agneta
dc.contributor.authorNordlund, Arto
dc.contributor.authorNovak, Gerald P.
dc.contributor.authorParaskevas, George P.
dc.contributor.authorParnetti, Lucilla
dc.contributor.authorPerera, Gayan
dc.contributor.authorPeters, Oliver
dc.contributor.authorPopp, Julius
dc.contributor.authorPrabhakar, Sudesh
dc.contributor.authorRabinovici, Gil D.
dc.contributor.authorRamakers, Inez H. G. B.
dc.contributor.authorRami, Lorena
dc.contributor.authorResende de Oliveira, Catarina
dc.contributor.authorRinne, Juha O.
dc.contributor.authorRodrigue, Karen M.
dc.contributor.authorRodríguez-Rodríguez, Eloy
dc.date.accessioned2021-05-28T12:58:26Z
dc.date.available2021-05-28T12:58:26Z
dc.date.issued2015
dc.descriptionCopyright © 2015 American Medical Association. All rights reserved.pt_PT
dc.description.abstractImportance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). Data sources: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. Study selection: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. Data extraction and synthesis: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. Main outcomes and measures: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. Results: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. Conclusions and relevance: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.pt_PT
dc.description.sponsorshipThe research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement No. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. BIOMARKAPD is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through national funding organizations under the aegis of JPND (http://www.jpnd.eu). In the Netherlands, this is ZonMw. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission as part of the 6th framework programme (contract No. 37670). This research was performed within the framework of the Center for Translational Molecular Medicine (CTTM) (http://www.ctmm.nl), project LeARN (grant 02N-101). The AIBL study was funded in part by the study partners (Australian Commonwealth Scientific Industrial and Research Organization [CSIRO], Edith Cowan University [ECU], Mental Health Research Institute [MHRI], Alzheimer’s Australia [AA], National Ageing Research Institute [NARI], Austin Health, CogState, Hollywood Private Hospital, Sir Charles Gardner Hospital). The study also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as ongoing funding from the Science and Industry Endowment Fund (SIEF). Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and the US Department of Defense ADNI (W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; BioClinica; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals; Eli Lilly; F. Hoffmann-La Roche and its affiliated company Genentech; GE Healthcare; Innogenetics; IXICO; Janssen Alzheimer Immunotherapy Research & Development; Johnson & Johnson Pharmaceutical Research & Development; Medpace; Merck; Meso Scale Diagnostics; NeuroRx Research; Novartis Pharmaceuticals; Pfizer; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The Dementia Competence Network (DCN) has been supported by a grant from the German Federal Ministry of Education and Research (BMBF): Kompetenznetz Demenzen (01GI0420). Additional funding related to the randomized clinical trials came from Janssen-Cilag and Merz Pharmaceuticals. The latter funds were exclusively used for personnel, pharmaceuticals, blistering and shipment of medication, and monitoring and as capitation fees for recruiting centers. Funding source for the Chandigarh study is the Indian Council of Medical Research (ICMR), India. Funding for the St Louis contribution was provided by the National Institute on Aging (P50 AG005681, P01 AG003991, and P01 AG026276); Fred Simmons and Olga Mohan, and the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Knight Alzheimer’s Disease Research Center. The Tours study received financial support of the French Ministry of Health grant PHRC-N 2008 1004 and the EC-FP6-project DiMI, LSHB-CT-2005-512146. The Caen study was funded by Agence Nationale de la Recherche, Programme Hospitalier de Recherche Clinique, Région Basse Normandie, and Institut National de la Santé et de la Recherche Médicale (Inserm). The research leading to the Munich contribution to the Mattsson multicenter study has received funding from the program “Investissements d’avenir” (ANR-10-IAIHU-06). The study from Pittsburgh was supported by National Institutes of Health grants (P50 AG005133, R37 AG025516, P01 AG025204). The New York contributions to the Mattsson multicenter study were in part supported by P30 AG008051, R01 AG13616, R01 AG022374, and R01 AG12101. Data from Brescia in this article were collected by Translational Outpatient Memory Clinic (TOMC) working group at IRCCS Fatebenefratelli in Brescia, Italy. Contributors to the TOMC are G. Amicucci, S. Archetti, L. Benussi, G. Binetti, L. Bocchio-Chiavetto, C. Bonvicini, E. Canu, F. Caobelli, E. Cavedo, E. Chittò, M. Cotelli, M. Gennarelli, S. Galluzzi, C. Geroldi, R. Ghidoni, R. Giubbini, U. P. Guerra, G. Kuffenschin, G. Lussignoli, D. Moretti, B. Paghera, M. Parapini, C. Porteri, M. Romano, S. Rosini, I. Villa, R. Zanardini, and O. Zanetti. The JPND Project is supported in Italy by the Italian Ministry of Health. The assembling of the TU Munich data set was supported in part by the German research foundation (Deutsche Forschungsgemeinschaft) (HE 4560/1-2, DR 445/3-1 and DR 445/4-1 to A.D.), and by a KKF grant for clinical research of the Technische Universität München (to A.D. and T.G.). The Florbetaben phase 2 study from which data were derived for this multicenter evaluation was sponsored by Bayer Healthcare/Piramal Imaging (Berlin, Germany). This work was supported by the University of Antwerp Research Fund; the Alzheimer Research Foundation (SAO-FRA); the Research Foundation Flanders (FWO); the Agency for Innovation by Science and Technology (IWT); the Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program; and the Flemish Government–initiated Methusalem excellence grant.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJAMA. 2015 May 19;313(19):1924-1938pt_PT
dc.identifier.doi10.1001/jama.2015.4668pt_PT
dc.identifier.eissn1538-3598
dc.identifier.issn0098-7484
dc.identifier.urihttp://hdl.handle.net/10451/48234
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Medical Associationpt_PT
dc.relationQLRT-2001-2455pt_PT
dc.relationEuropean Medical Information Framework
dc.relationCombinatorics and geometry in semigroup theory
dc.relation.publisherversionhttps://jamanetwork.com/journals/jamapt_PT
dc.titlePrevalence of cerebral amyloid pathology in persons without dementiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber115372
oaire.awardNumberPOCTI/MAT/37670/2001
oaire.awardTitleEuropean Medical Information Framework
oaire.awardTitleCombinatorics and geometry in semigroup theory
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/115372/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCTI%2FMAT%2F37670%2F2001/PT
oaire.citation.endPage1938pt_PT
oaire.citation.issue19pt_PT
oaire.citation.startPage1924pt_PT
oaire.citation.titleJournal of the American Medical Associationpt_PT
oaire.citation.volume313pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamPOCI
person.familyNamede Mendonça
person.givenNameAlexandre
person.identifier.ciencia-id1615-41B4-0848
person.identifier.orcid0000-0002-0488-1453
person.identifier.scopus-author-id7003320823
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication53ca3547-99ce-4b68-9330-7879a54c47b7
relation.isAuthorOfPublication.latestForDiscovery53ca3547-99ce-4b68-9330-7879a54c47b7
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