Show simple item record

dc.contributor.authorMutsaerts, Henri JMM
dc.contributor.authorMirza, Saira S
dc.contributor.authorPetr, Jan
dc.contributor.authorThomas, David L
dc.contributor.authorCash, David M
dc.contributor.authorBocchetta, Martina
dc.contributor.authorde Vita, Enrico
dc.contributor.authorMetcalfe, Arron WS
dc.contributor.authorShirzadi, Zahra
dc.contributor.authorRobertson, Andrew D
dc.contributor.authorTartaglia, Maria Carmela
dc.contributor.authorMitchell, Sara B
dc.contributor.authorBlack, Sandra E
dc.contributor.authorFreedman, Morris
dc.contributor.authorTang-Wai, David
dc.contributor.authorKeren, Ron
dc.contributor.authorRogaeva, Ekaterina
dc.contributor.authorvan Swieten, John
dc.contributor.authorLaforce, Robert
dc.contributor.authorTagliavini, Fabrizio
dc.contributor.authorBorroni, Barbara
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorRowe, James
dc.contributor.authorGraff, Caroline
dc.contributor.authorFrisoni, Giovanni B
dc.contributor.authorFinger, Elizabeth
dc.contributor.authorSorbi, Sandro
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorRohrer, Jonathan D
dc.contributor.authorMacIntosh, Bradley J
dc.contributor.authorMasellis, Mario
dc.contributor.authorGENetic Frontotemporal dementia Initiative (GENFI)
dc.date.accessioned2019-03-26T00:30:08Z
dc.date.available2019-03-26T00:30:08Z
dc.date.issued2019-04-01
dc.identifier.issn0006-8950
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290816
dc.description.abstractGenetic forms of frontotemporal dementia are most commonly due to mutations in three genes, C9orf72, GRN or MAPT, with presymptomatic carriers from families representing those at risk. While cerebral blood flow shows differences between frontotemporal dementia and other forms of dementia, there is limited evidence of its utility in presymptomatic stages of frontotemporal dementia. This study aimed to delineate the cerebral blood flow signature of presymptomatic, genetic frontotemporal dementia using a voxel-based approach. In the multicentre GENetic Frontotemporal dementia Initiative (GENFI) study, we investigated cross-sectional differences in arterial spin labelling MRI-based cerebral blood flow between presymptomatic C9orf72, GRN or MAPT mutation carriers (n = 107) and non-carriers (n = 113), using general linear mixed-effects models and voxel-based analyses. Cerebral blood flow within regions of interest derived from this model was then explored to identify differences between individual gene carrier groups and to estimate a timeframe for the expression of these differences. The voxel-based analysis revealed a significant inverse association between cerebral blood flow and the expected age of symptom onset in carriers, but not non-carriers. Regions included the bilateral insulae/orbitofrontal cortices, anterior cingulate/paracingulate gyri, and inferior parietal cortices, as well as the left middle temporal gyrus. For all bilateral regions, associations were greater on the right side. After correction for partial volume effects in a region of interest analysis, the results were found to be largely driven by the C9orf72 genetic subgroup. These cerebral blood flow differences first appeared approximately 12.5 years before the expected symptom onset determined on an individual basis. Cerebral blood flow was lower in presymptomatic mutation carriers closer to and beyond their expected age of symptom onset in key frontotemporal dementia signature regions. These results suggest that arterial spin labelling MRI may be a promising non-invasive imaging biomarker for the presymptomatic stages of genetic frontotemporal dementia.
dc.format.mediumPrint
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.subjectGENetic Frontotemporal dementia Initiative (GENFI)
dc.subjectBrain
dc.subjectHumans
dc.subjecttau Proteins
dc.subjectMagnetic Resonance Imaging
dc.subjectCross-Sectional Studies
dc.subjectNeuropsychological Tests
dc.subjectCerebrovascular Circulation
dc.subjectHeterozygote
dc.subjectMutation
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectFrontotemporal Dementia
dc.subjectC9orf72 Protein
dc.subjectProgranulins
dc.titleCerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study.
dc.typeArticle
prism.endingPage1120
prism.issueIdentifier4
prism.publicationDate2019
prism.publicationNameBrain
prism.startingPage1108
prism.volume142
dc.identifier.doi10.17863/CAM.38007
dcterms.dateAccepted2019-01-04
rioxxterms.versionofrecord10.1093/brain/awz039
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-04
dc.contributor.orcidRowe, James [0000-0001-7216-8679]
dc.identifier.eissn1460-2156
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (088324/Z/09/Z)
pubs.funder-project-idMRC (via University College London (UCL)) (523989)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idMedical Research Council (MR/J009482/1)
pubs.funder-project-idMedical Research Council (MR/M009041/1)
pubs.funder-project-idMedical Research Council (MR/M024873/1)
cam.issuedOnline2019-03-07
cam.orpheus.successThu Jan 30 10:48:22 GMT 2020 - Embargo updated
rioxxterms.freetoread.startdate2020-04-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record