Accelerated cortical thinning in FTD-3 CHMP2B mutation carriers

Peter Johannsen, Simon Fristed Eskildsen, Jørgen E. Nielsen, Adrian Isaacs, Dora Zeidler, Leif Østergaard

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Background: Frontotemporal dementia linked to chromosome 3 (FTD-3) (1) is caused by mutations in the CHMP2B gene in the endosomal ESCRT-III complex (2). Objective: To prospectively study changes over time of cortical thickness in structural neuroimaging MR data from the large Danish FTD-3 family with a pathogenic G-to-C transition in the acceptor splice site of CHMP2B exon 6. Methods: Nine presymptomatic CHMP2B mutation carriers (mean age 55.8 ± SD 5.6) and 7 mutation negative (MN) (mean age 54.3 ± SD 6.0) family members were scanned twice, 1.3 years apart, using a 3T MRI FSPGR 3D sequence. Cortical thickness was calculated with an updated previously published method (3) where 3D non-parametric surfaces were iteratively fitted to the inner and outer boundary of the cortex. The method calculates the cortical thickness with sub-voxel accuracy at more than 85.000 vertices equally distributed over the cortical surface. For this abstract results were pooled for right and left cortical lobes as defined by a stereotaxic atlas. Results: Paired t-tests between cortical thicknesses at the two time points showed that for CHMP2B mutation carriers all lobes except the parietal and the right temporal were significantly thinner at time point 2 compared to 1. In the MN group only the left occipital lobe was significantly thinner at time point 2. Annualized thinning rates (mean±SD) as percent decline of thickness at time point 1 are listed in Table.

Conclusions: The cortical thinning rate is significantly higher in the left frontal and left temporal lobe in CHMP2B mutation carriers compared to the mutation negative subjects. Supported by Danish MRC: 22-04-0458.
Original languageEnglish
JournalAlzheimer's & Dementia
Issue4(Suppl. 1)
Pages (from-to)T82 No. IC-P3-187 and T425 No. P2-186
Publication statusPublished - Jul 2008
Externally publishedYes


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