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Background: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. Objectives: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. Methods: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A &nvge;10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. Results: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. Conclusions: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration. [ABSTRACT FROM AUTHOR]

Background: Given the multifaceted nature of this inherited neurodegenerative condition, typically affecting adults in mid-life, it is perhaps not surprising that studies indicate poorer Health Related Quality of Life (HrQoL) in those with the gene-expansion and, by association, in their families. Objective: This study aimed to extend the current literature by exploring specific life domains, including at an earlier disease stage than usually reported in the HRQoL literature, and in a subgroup of gene-negative partners. Methods: 355 participants from the TRACK-HD cohort (120 Controls, 118 Pre-HD and 117 early-HD) completed standardised self-report measures of HrQoL (SF36 and QoLI), underwent clinical assessments of capacity and motor function (UHDRS), semi structured interviews assessing neuropsychiatric symptoms (PBA-s), completed paper and computerized cognitive tasks and assessment of behaviours associated with damage to frontal brain circuits (FrSBe). Results: Each gene-expanded group scored statistically significantly lower than gene-negative sibling controls on the SF36 General Health subscale; neuropsychiatric symptoms and executive dysfunction were associated with reduced HrQoL. Those with Stage II disease reported statistically significantly lower HrQoL than gene-negative controls across physical, emotional and social life domains. Those partnered with manifest participants reported lower HrQoL in the social domain compared to those partnered with at-risk participants furthest from disease onset; and perseverative symptoms in manifest partners were found to be related to lower HrQoL in their gene-negative partners. HrQoL in gene-negative partners of pre-manifest individuals was associated with pre-manifest individuals' neuropsychiatric and cognitive function. Conclusions: Understanding the nature and timing of disruption to the HrQoL in people who are pre-manifest and diagnosed with HD, and their gene-negative partners, can inform the development of appropriate strategies and interventions. [ABSTRACT FROM AUTHOR]