Limbic system changes in Huntington's disease: diffusion tensor MRI data with ROI analysis
Abstract
Introduction. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder in which early affective and cognitive symptoms may be associated with limbic system involvement; however, the pattern of microstructural changes in its major white matter pathways remains insufficiently understood. The aim of the study was to assess the state of limbic system tracts (cingulum, fornix, and inferior longitudinal fasciculus) in patients at manifest and premanifest stages of HD using diffusion tensor MRI (DT-MRI) and region-of-interest (ROI) analysis. Materials and methods. A total of 64 individuals were examined: 24 patients with manifest HD, 20 premanifest mutation carriers, and 20 healthy volunteers matched for sex and age. All subjects underwent DT-MRI on a Siemens Magnetom Prisma 3T scanner (64 diffusion directions, b-values 1000 and 2500 s/mm2), followed by data adjustment and normalization to MNI space. ROI analysis of the cingulum, fornix, and inferior longitudinal fasciculus was performed using DSI Studio software, extracting fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Correlations with clinical scales (UHDRS, MoCA, FAB, HADS, Schulte tables) and genetic markers (CAG repeat length, CAP score) were assessed. Results. In manifest patients, the cingulum showed decreased FA and increased RD, indicating predominant demyelination, whereas the inferior longitudinal fasciculus exhibited concurrent increases in both AD and RD, suggesting more severe axonal and myelin damage. In premanifest mutation carriers, the earliest changes were detected in the fornix crura (decreased FA) and in the anterior portion of the inferior longitudinal fasciculus (increased RD and MD). Significant correlations were found between diffusion metrics and anxiety and depression scores (HADS), cognitive performance (MoCA, FAB), and genetic burden (CAG repeat length, CAP score). Conclusion. These findings confirm the heterogeneous and stage-dependent nature of limbic tract involvement in HD, supporting the potential use of DT-MRI as a tool for preclinical diagnosis and monitoring of non-motor manifestations of the disease.