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dc.contributor.authorHarper, Len
dc.contributor.authorBouwman, Fen
dc.contributor.authorBurton, EJen
dc.contributor.authorBarkhof, Fen
dc.contributor.authorScheltens, Pen
dc.contributor.authorO'Brien, Johnen
dc.contributor.authorFox, NCen
dc.contributor.authorRidgway, GRen
dc.contributor.authorSchott, JMen
dc.description.abstract$\textbf{OBJECTIVE}$: Imaging is recommended to support the clinical diagnoses of dementias, yet imaging research studies rarely have pathological confirmation of disease. This study aims to characterise patterns of brain volume loss in six primary pathologies compared with controls and to each other. $\textbf{METHODS}$: One hundred and eighty-six patients with a clinical diagnosis of dementia and histopathological confirmation of underlying pathology, and 73 healthy controls were included in this study. Voxel-based morphometry, based on ante-mortem T1-weighted MRI, was used to identify cross-sectional group differences in brain volume. $\textbf{RESULTS}$: Early-onset and late-onset Alzheimer's disease exhibited different patterns of grey matter volume loss, with more extensive temporoparietal involvement in the early-onset group, and more focal medial temporal lobe loss in the late-onset group. The Presenilin-1 group had similar parietal involvement to the early-onset group with localised volume loss in the thalamus, medial temporal lobe and temporal neocortex. Lewy body pathology was associated with less extensive volume loss than the other pathologies, although precentral/postcentral gyri volume was reduced in comparison with other pathological groups. Tau and TDP43A pathologies demonstrated similar patterns of frontotemporal volume loss, although less extensive on the right in the 4-repeat-tau group, with greater parietal involvement in the TDP43A group. The TDP43C group demonstrated greater left anterior-temporal involvement. $\textbf{CONCLUSIONS}$: Pathologically distinct dementias exhibit characteristic patterns of regional volume loss compared with controls and other dementias. Voxelwise differences identified in these cohorts highlight imaging signatures that may aid in the differentiation of dementia subtypes during life. The results of this study are available for further examination via NeuroVault (
dc.description.sponsorshipThe Dementia Research Centre is an Alzheimer’s Research UK coordinating centre. The authors acknowledge the support of Alzheimer’s Research UK (grant number ART-NCG2010B-2), the Medical Research Council (grant number MR/J014257/2), the NIHR Queen Square Dementia Biomedical Research Unit, UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre, the NIHR Newcastle Biomedical Research Unit in Lewy body dementia and the NIHR Cambridge Biomedical Research Unit in Dementia. LH is supported by funding from Alzheimer’s Research UK and a UCL Impact Studentship. NCF and JTOB hold NIHR Senior Investigator Awards. JMS acknowledges the support of the NIHR Queen Square Dementia BRU, the NIHR UCL/H Biomedical Research Centre, Wolfson Foundation, EPSRC (EP/J020990/1), MRC (CSUB19166), ARUK (ARUK-Network 2012–6-ICE; ARUK-PG2014-1946) and European Commission (H2020-PHC-2014-2015-666992).
dc.publisherBMJ Publishing Group
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.subjectAlzheimer’s diseaseen
dc.subjectbrain atrophyen
dc.titlePatterns of atrophy in pathologically confirmed dementias: a voxelwise analysisen
prism.publicationNameJournal of Neurology, Neurosurgery and Psychiatryen
dc.contributor.orcidO'Brien, John [0000-0002-0837-5080]
rioxxterms.typeJournal Article/Reviewen
cam.orpheus.successThu Jan 30 12:53:48 GMT 2020 - The item has an open VoR version.*

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International