Identification And Evaluation Of Biomarkers For Huntingtons Disease PDF Download

Recent research findings have challenged the conventional view of Huntington's Disease (HD) as a disease primarily of the basal ganglia and striatal-frontal circuits. Use of cortical thickness mapping (an automated MRI technique) has revealed significant cortical thinning in the posterior cortex even in pre-symptomatic HD (Rosas et al., 2005). Three years ago Davison (2009) found posterior cortical thinning in a pre-symptomatic HD (PreHD) sample, accompanied by poorer performance on some cognitive tasks thought to depend upon posterior brain regions, with unimpaired performance on anterior tasks, suggesting there may be functional effects of cortical changes identified by neuroimaging. The research in this thesis involves a follow-up study to Davison, involving the same PreHD (n=18) and matched Control participants (n=17). The same neuropsychological measures used in the first assessment were administered to examine cognitive and mood changes over the three years. Based on the logic that the cortical thinning identified at the first assessment was due to the HD gene, and the poorer performance on tasks selected to recruit these brain regions was a consequence of that thinning, it was predicted that poorer performance would be evident in the PreHD group on the same cognitive tasks at the second time-point. Given the PreHD participants have progressed towards clinical onset, it was also hypothesised that performance on posterior tasks would have declined, particularly in individuals closest to clinical onset. Lastly, we predicted the PreHD group would be unimpaired on tasks sensitive to anterior brain regions Consistent with these predictions, the pre-symptomatic group performed more poorly than Controls on three tasks sensitive to posterior brain regions (Judgement of Line Orientation Test, Roadmap test and Benton Facial Recognition). Decline was evident on two tasks (Roadmap test and Benton Facial Recognition), most pronounced for those close to clinical onset, while PreHD performance was unremarkable on anterior tasks. These findings suggest there are functional consequences of posterior cortical thinning found in pre-symptomatic HD. The findings also reveal potential candidates for cognitive biomarkers that may be sensitive to detecting, and tracking, progression of functional changes resulting from cortical changes occurring very early in the disease.