Differential early subcortical involvement in genetic FTD within the GENFI cohort
| Main Author: | |
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| Publication Date: | 2021 |
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10451/47560 |
Summary: | © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
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Differential early subcortical involvement in genetic FTD within the GENFI cohortBrain volumetryGenetic frontotemporal dementiaMRI imagingPresymptomatic stage© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, the Alzheimer's Society grant (AS-PG-16-007), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). MB is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). MB’s work was also supported 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. MB acknowledges the support of NVIDIA Corporation with the donation of the Titan V GPU used for part of the analyses in this research. JDR is an MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration. JEI is supported by the European Research Council (Starting Grant 677697, project BUNGEE-TOOLS), Alzheimer’s Research UK (ARUK-IRG2019A003) and NIH 1RF1MH123195-01. JBR is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). Several authors of this publication (JCvS, MS, RSV, AD, MO, JDR) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.ElsevierRepositório da Universidade de LisboaBocchetta, MartinaTodd, Emily G.Peakman, GeorgiaCash, David M.Convery, Rhian S.Russell, Lucy L.Thomas, David L.Iglesias, Juan Eugeniovan Swieten, John C.Jiskoot, Lize C.Seelaar, HarroBorroni, BarbaraGalimberti, DanielaSanchez-Valle, RaquelLaforce, RobertMoreno, FerminSynofzik, MatthisGraff, CarolineMasellis, MarioTartaglia, Maria CarmelaRowe, James B.Vandenberghe, RikFinger, ElizabethTagliavini, FabrizioDe Mendonça, AlexandreSantana, IsabelButler, Chris R.Ducharme, SimonGerhard, AlexanderDanek, AdrianLevin, JohannesOtto, MarkusSorbi, SandroLe Ber, IsabellePasquier, FlorenceRohrer, Jonathan D.2021-04-27T11:22:22Z2021-03-292021-03-29T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47560engNeuroimage Clin. 2021 Mar 29;30:10264610.1016/j.nicl.2021.1026462213-1582info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:32:43Zoai:repositorio.ulisboa.pt:10451/47560Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:14:38.823987Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| title |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| spellingShingle |
Differential early subcortical involvement in genetic FTD within the GENFI cohort Bocchetta, Martina Brain volumetry Genetic frontotemporal dementia MRI imaging Presymptomatic stage |
| title_short |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| title_full |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| title_fullStr |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| title_full_unstemmed |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| title_sort |
Differential early subcortical involvement in genetic FTD within the GENFI cohort |
| author |
Bocchetta, Martina |
| author_facet |
Bocchetta, Martina Todd, Emily G. Peakman, Georgia Cash, David M. Convery, Rhian S. Russell, Lucy L. Thomas, David L. Iglesias, Juan Eugenio van Swieten, John C. Jiskoot, Lize C. Seelaar, Harro Borroni, Barbara Galimberti, Daniela Sanchez-Valle, Raquel Laforce, Robert Moreno, Fermin Synofzik, Matthis Graff, Caroline Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Vandenberghe, Rik Finger, Elizabeth Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Butler, Chris R. Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Otto, Markus Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Rohrer, Jonathan D. |
| author_role |
author |
| author2 |
Todd, Emily G. Peakman, Georgia Cash, David M. Convery, Rhian S. Russell, Lucy L. Thomas, David L. Iglesias, Juan Eugenio van Swieten, John C. Jiskoot, Lize C. Seelaar, Harro Borroni, Barbara Galimberti, Daniela Sanchez-Valle, Raquel Laforce, Robert Moreno, Fermin Synofzik, Matthis Graff, Caroline Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Vandenberghe, Rik Finger, Elizabeth Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Butler, Chris R. Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Otto, Markus Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Rohrer, Jonathan D. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Bocchetta, Martina Todd, Emily G. Peakman, Georgia Cash, David M. Convery, Rhian S. Russell, Lucy L. Thomas, David L. Iglesias, Juan Eugenio van Swieten, John C. Jiskoot, Lize C. Seelaar, Harro Borroni, Barbara Galimberti, Daniela Sanchez-Valle, Raquel Laforce, Robert Moreno, Fermin Synofzik, Matthis Graff, Caroline Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Vandenberghe, Rik Finger, Elizabeth Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Butler, Chris R. Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Otto, Markus Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Rohrer, Jonathan D. |
| dc.subject.por.fl_str_mv |
Brain volumetry Genetic frontotemporal dementia MRI imaging Presymptomatic stage |
| topic |
Brain volumetry Genetic frontotemporal dementia MRI imaging Presymptomatic stage |
| description |
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| publishDate |
2021 |
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2021-04-27T11:22:22Z 2021-03-29 2021-03-29T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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http://hdl.handle.net/10451/47560 |
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eng |
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eng |
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Neuroimage Clin. 2021 Mar 29;30:102646 10.1016/j.nicl.2021.102646 2213-1582 |
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Elsevier |
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