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Thalamic atrophy in frontotemporal dementia - not just a C9orf72 problem

Bocchetta, M; Gordon, E; Cardoso, MJ; Modat, M; Ourselin, S; Warren, J; Rohrer, J; (2018) Thalamic atrophy in frontotemporal dementia - not just a C9orf72 problem. NeuroImage: Clinical , 18 pp. 675-681. 10.1016/j.nicl.2018.02.019. Green open access

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Abstract

BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder associated with frontal and temporal atrophy. Subcortical involvement has been described as well, with early thalamic atrophy most commonly associated with the C9orf72 expansion. However thalamic involvement has not been comprehensively investigated across the FTD spectrum. METHODS: We investigated thalamic volumes in a sample of 341 FTD patients (age: mean(standard deviation) 64.2(8.5) years; disease duration: 4.6(2.7) years) compared with 99 age-matched controls (age: 61.9(11.4) years). We performed a parcellation of T1 MRIs using an atlas propagation and label fusion approach to extract left and right thalamus volumes, which were corrected for total intracranial volumes. We assessed subgroups stratified by clinical diagnosis (141 behavioural variant FTD (bvFTD), 76 semantic dementia (SD), 103 progressive nonfluent aphasia (PNFA), 7 with associated motor neurone disease (FTD-MND) and 14 primary progressive aphasia not otherwise specified (PPA-NOS), genetic diagnosis (24 with MAPT, 24 with C9orf72, and 15 with GRN mutations), and pathological diagnosis (40 tauopathy, 61 TDP-43opathy, 3 FUSopathy). We assessed the diagnostic accuracy based on thalamic volume. RESULTS: Overall, FTD patients had smaller thalami than controls (8% difference in volume, p < 0.0005, ANCOVA). Stratifying by genetics, C9orf72 group had the smallest thalami (14% difference from controls, p < 0.0005). However, the thalami were also smaller than controls in the other genetic groups: GRN and MAPT groups showed a difference of 11% and 9% respectively (p < 0.0005). ROC analysis showed a relatively poor ability to separate C9orf72 from MAPT (AUC = 0.651, p = 0.073) and from GRN cases (AUC = 0.644, p = 0.133) using thalamic volume. All clinical subtypes had significantly smaller thalami than controls (p < 0.0005), with the FTD-MND group having the smallest (15%), followed by bvFTD (9%), PNFA (8%), PPA-NOS (7%), and lastly SD (5%). In the pathological groups, the TDP-43opathies had an 11% difference from controls, and tauopathies 9%, while the FUSopathies showed only 2% of difference from controls (p < 0.0005). GRN, PPA-NOS and SD were the subgroups showing the highest asymmetry in volumes. CONCLUSIONS: The thalamus was most affected in C9orf72 genetically, TDP-43opathies pathologically and FTD-MND clinically. However, thalamic atrophy is a common feature across all FTD groups.

Type: Article
Title: Thalamic atrophy in frontotemporal dementia - not just a C9orf72 problem
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nicl.2018.02.019
Publisher version: https://doi.org/10.1016/j.nicl.2018.02.019
Language: English
Additional information: This version is the author accepted manuscript available under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Frontotemporal dementia, MRI, Thalamus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10045245
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