Orbitofrontal atrophy on MRI appears to be an indicator of C9orf72 repeat expansion status in FTD

Frontotemporal dementia (FTD) is an important group of neurodegenerative diseases causing early onset dementia. While FTD is mostly sporadic, a common cause of genetic FTD is the C9orf72 hexanucleotide repeat expansion (C9exp). To date, no imaging biomarkers have been identified for differentiating between sporadic and hereditary cases. In this study, we focused on MRI-based neuroanatomical comparisons between FTD subtypes bvFTD and nfvPPA, as well as the C9exp status, to identify potential imaging biomarkers. Fifty-six patients with FTD (43 bvFTD and 13 nfvPPA) underwent clinical evaluation and magnetic resonance imaging (MRI) at 1,5T and 3,0T The genetically analysed subgroup consisted of 13 C9exp -positive and 22 C9exp -negative cases. cNeuro® cMRI software was used for comprehensive voxel-based morphometry (VBM) analyses of the MRI images for multiple brain regions, structures and their volumes. Our results show that orbitofrontal volumes, particularly of the right anterior and posterior orbital gyri, demonstrate high sensitivity (90,9-100%) and specificity (76,9%) in differentiating C9exp cases from sporadic FTD. Furthermore, we elucidated and corroborated several statistically significant volumetric differences in multiple brain regions between the FTD subtypes of bvFTD and nfvPPA, such as asymmetrical, right-sided atrophy in the former. This is the first demonstration that C9exp-positive FTD cases can be reliably differentiated from sporadic cases based solely on MRI atrophy patterns. Furthermore, we corroborate several diagnostically significant volumetric differences in brain regions between bvFTD and nfvPPA variants, providing evidence that advanced brain morphometry techniques constitute a valuable tool for identifying even more FTD subtypes.