E007 The role of temporal white matter in Huntington’s disease cognitive deficits

<h3>Background</h3> Cognitive decline, including language and memory deficits, in Huntington’s disease (HD) has traditionally been associated with fronto-striatal circuits neurodegeneration, while temporal regions involved in these functions were thought to be preserved. However, recent studies suggest that HD pathology extends to temporal and hippocampal regions. The extent to which cognitive deficits in HD are explained by alterations in temporal white matter connections remains unclear. <h3>Aims</h3> This study investigates the vulnerability of macro- and microstructural changes in medial temporal lobe (MTL) pathways and hippocampal interhemispheric connections (fornix), and whether variability of these connections explains cognitive deficits in HD patients. <h3>Methods</h3> Forty-six HD individuals (23 premanifest, 23 manifest) were evaluated for memory and language using Hopkins Verbal Learning Test and Boston Naming Test, respectively. Diffusion tensor imaging was used to delineate temporal projections through probabilistic tractography. Macrostructural (volume) and microstructural diffusion biomarkers (Fractional Anisotropy, Radial diffusivity) were extracted for each tract, and Principal Component Analyses (PCA) were conducted to identify patterns of alterations. These patterns were related to clinical symptoms using multivariate linear models. <h3>Results</h3> We observed both memory and language changes, as well as widespread structural changes in temporal white matter, when comparing premanifest and manifest HD individuals. PCA identified three factors differentiating MTL pathways and fornix microstructural variability. Fornix volume predicted language and memory bilaterally. Additionally, while language deficits were related with bilateral MLT miscrostuctural patterns, memory changes were associated with the right MTL. <h3>Conclusions</h3> These results underscore the importance of temporal white matter connectivity in HD cognitive symptoms and may help to better understand the associated fronto-striatal deficits.