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000282328 1001_ $$aSoskic, Sonja$$b0
000282328 245__ $$aThalamus involvement in genetic frontotemporal dementia assessed using structural and diffusion MRI: a GENFI study.
000282328 260__ $$a[Oxford]$$bOxford University Press$$c2025
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000282328 520__ $$aThalamic subregions are commonly, but variably, affected by different forms of frontotemporal dementia. We aimed to better characterize thalamic subregional involvement in genetic frontotemporal dementia with a recently published thalamus segmentation tool that utilizes structural and diffusion MRI, offering additional assessment of mean diffusivity and a more fine-grained analysis of the pulvinar specifically compared to previous studies. Using this tool, we performed thalamus segmentations in MRI scans from C9orf72, GRN and MAPT mutation carriers and mutation non-carriers with suitable 3-Tesla MRI cross-sectional data from the GENetic Frontotemporal dementia Initiative. Mutation carriers were divided according to their genetic group and Clinical Dementia Rating® Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behaviour and Language Domains global score (0 or 0.5: presymptomatic/prodromal stage, 1 or higher: symptomatic stage). Following stringent quality control and harmonization across sites and scanners, we compared volumes and mean diffusivity values of thalamic subregions in C9orf72 (47 presymptomatic, 10 symptomatic), GRN (57 presymptomatic, 11 symptomatic) and MAPT (31 presymptomatic, 12 symptomatic) mutation carriers to those in 109 mutation non-carriers with analyses of covariance including age and sex (and total intracranial volume for volumetric comparisons) as covariates. Presymptomatic C9orf72 expansion carriers showed smaller volumes (3-8% difference from non-carriers) and higher mean diffusivity (2-5% difference from non-carriers) for several thalamic subregions, including all pulvinar subdivisions. We found subtly larger volumes of the ventral anterior subregion and the non-medial pulvinar (3% difference from non-carriers for both) in presymptomatic GRN mutation carriers, and of the anteroventral subregion (5% difference from non-carriers) in presymptomatic MAPT mutation carriers. Symptomatic mutation carriers in all three genetic groups showed significantly smaller volumes and widespread higher mean diffusivity of thalamic subregions compared with non-carriers, which were overall most prominent in subregions involved in associative and limbic functions (the midline, medial pulvinar, anteroventral, mediodorsal, laterodorsal and lateral posterior subregions). Notably smaller volume (12-23% difference from non-carriers) and higher mean diffusivity (16-23% difference from non-carriers) of the most medial part of the medial pulvinar was a shared feature across the three genetic groups at the symptomatic stage. Overall, our study confirms that thalamic subregions are affected in genetic frontotemporal dementia and identifies prominent involvement of the most medial part of the medial pulvinar as a potential unifying feature in the variable pattern of thalamic subregional involvement across the main genetic groups.
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000282328 650_7 $$2Other$$aMRI
000282328 650_7 $$2Other$$adiffusion tensor imaging
000282328 650_7 $$2Other$$afrontotemporal dementia
000282328 650_7 $$2Other$$agenetics
000282328 650_7 $$2Other$$athalamus
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000282328 7001_ $$aRussell, Lucy L$$b5
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000282328 7001_ $$00000-0001-7512-7856$$aMalone, Ian B$$b7
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000282328 7001_ $$aFerry-Bolder, Eve$$b9
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000282328 7001_ $$00000-0001-7750-896X$$aSanchez-Valle, Raquel$$b13
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000282328 7001_ $$00000-0001-6237-2502$$aVandenberghe, Rik$$b17
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000282328 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b22
000282328 7001_ $$aNacmias, Benedetta$$b23
000282328 7001_ $$aOtto, Markus$$b24
000282328 7001_ $$00000-0002-5283-503X$$aBertoux, Maxime$$b25
000282328 7001_ $$aLebouvier, Thibaud$$b26
000282328 7001_ $$00000-0002-7309-1113$$aDucharme, Simon$$b27
000282328 7001_ $$00000-0002-7502-9284$$aButler, Christopher R$$b28
000282328 7001_ $$aLe Ber, Isabelle$$b29
000282328 7001_ $$00000-0003-4461-7427$$aFinger, Elizabeth C$$b30
000282328 7001_ $$aTartaglia, Maria Carmela$$b31
000282328 7001_ $$aMasellis, Mario$$b32
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000282328 7001_ $$aAlexander, Daniel C$$b37
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000282328 7001_ $$aRohrer, Jonathan D$$b39
000282328 7001_ $$00000-0003-1814-5024$$aBocchetta, Martina$$b40
000282328 7001_ $$aInitiative, GENetic Frontotemporal dementia$$b41$$eCollaboration Author
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