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Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes

2020Artigo científico Acesso aberto
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dc.contributor.authorMalpetti, Maura
dc.contributor.authorJones, P. Simon
dc.contributor.authorTsvetanov, Kamen A.
dc.contributor.authorRittman, Timothy
dc.contributor.authorSwieten, John C.
dc.contributor.authorBorroni, Barbara
dc.contributor.authorSanchez‐Valle, Raquel
dc.contributor.authorMoreno, Fermin
dc.contributor.authorLaforce, Robert
dc.contributor.authorGraff, Caroline
dc.contributor.authorSynofzik, Matthis
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorMasellis, Mario
dc.contributor.authorTartaglia, Maria Carmela
dc.contributor.authorFinger, Elizabeth
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorMendonça, Alexandre de
dc.contributor.authorTagliavini, Fabrizio
dc.contributor.authorSantana, Isabel
dc.contributor.authorDucharme, Simon
dc.contributor.authorButler, Chris R.
dc.contributor.authorGerhard, Alexander
dc.contributor.authorLevin, Johannes
dc.contributor.authorDanek, Adrian
dc.contributor.authorOtto, Markus
dc.contributor.authorFrisoni, Giovanni B.
dc.contributor.authorGhidoni, Roberta
dc.contributor.authorSorbi, Sandro
dc.contributor.authorHeller, Carolin
dc.contributor.authorTodd, Emily G.
dc.contributor.authorBocchetta, Martina
dc.contributor.authorCash, David M.
dc.contributor.authorConvery, Rhian S.
dc.contributor.authorPeakman, Georgia
dc.contributor.authorMoore, Katrina M.
dc.contributor.authorRohrer, Jonathan D.
dc.contributor.authorKievit, Rogier A.
dc.contributor.authorRowe, James B.
dc.contributor.authorGENFI - Genetic Frontotemporal dementia Initiative
dc.date.accessioned2020-12-17T17:29:05Z
dc.date.available2020-12-17T17:29:05Z
dc.date.issued2020
dc.description© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.pt_PT
dc.description.abstractIntroduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD.pt_PT
dc.description.sponsorshipThis work is co‐funded by the UK Medical Research Council (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and the Bluefield Project, as well as a JPND grant “GENFI‐prox” (by DLR/BMBF to MS, joined with JDR, JvS, MO, BB and CG). MM is supported by the Cambridge Trust & Sidney Sussex College Scholarship. PSJ is supported by the Cambridge Centre for Parkinson Plus. KAT is supported by the British Academy Postdoctoral Fellowship (KAT: PF160048) and Guarantors of Brain (KAT: 101149). TR is supported by the Cambridge Centre for Parkinson Plus and Cambridge Biomedical Resource Centre. RAK is supported by Medical Research Council (RAK: SUAG/047/G101400). JBR reports grants from the NIHR Cambridge Biomedical research centre, Wellcome Trust (103838), and Medical Research Council (SUAG051/G101400; MR/T033371/1); personal fees from Asceneuron, WAVE, Astex, and Biogen; and grants from Janssen, AZ Medimmune, and Eli Lilly, outside the submitted work. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS‐JF‐19a‐004‐517), and by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlzheimer’s Dement. 2020;00-00.pt_PT
dc.identifier.doi10.1002/alz.12252pt_PT
dc.identifier.eissn2352-8729
dc.identifier.issn1552-5260
dc.identifier.urihttp://hdl.handle.net/10451/45431
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relation.publisherversionhttps://alz-journals.onlinelibrary.wiley.com/journal/15525279pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectApathypt_PT
dc.subjectCognitive declinept_PT
dc.subjectGenetic frontotemporal dementiapt_PT
dc.subjectLongitudinal designpt_PT
dc.subjectMRIpt_PT
dc.subjectPresymptomatic carrierspt_PT
dc.titleApathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleAlzheimer's & Dementiapt_PT
person.familyNamede Mendonça
person.givenNameAlexandre
person.identifier.ciencia-id1615-41B4-0848
person.identifier.orcid0000-0002-0488-1453
person.identifier.scopus-author-id7003320823
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication53ca3547-99ce-4b68-9330-7879a54c47b7
relation.isAuthorOfPublication.latestForDiscovery53ca3547-99ce-4b68-9330-7879a54c47b7

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