The purpose of the proposed Neuroimaging Project is to use quantitative measures from MRI to chart the longitudinal course of atrophy in specific brain structures in patients with Huntington's Disease. In conjunction with Project (Neuropsychology) and Core (Clinical), we will also determine the association between these neuroanatomical changes and longitudinal changes in neuropsychological functioning and clinical symptomatology. We will obtain MRI scans on 150 patients with Huntington's Disease, and on 150 individually matched control subjects. Patients will be scanned every two years using the same standardized MRI protocol. MRI measurements will include volumes of basal ganglia (caudate, putamen, globus pallidus), brain stem, cerebellum, and comparison regions, as well as total gray, white, and CSF volumes, and volumes of specific cortical regions. MRI measures will be correlated and neuropsychological measures obtained at the same visit. We hypothesize that MRI measures of specific brain regions will correlate with specific neuropsychological functions, clinical variables, and length of trinucleotide repeat for the HD patients. Longitudinal changes in MRI measures will also be analyzed. We hypothesize that atrophy in various regions of the brain will progress at different rates during the course of the illness. We also hypothesize that rate of atrophy in specific brain regions will be correlated with rate of decline in specific neuropsychological functions. This project will provide the first systematic view of atrophy in several specific brain regions within the same HD patients over time. By comparing decline in specific neuropsychological functions and clinical symptoms with atrophy in specific regions that may deteriorate at different rates and at different points during the course of the illness, we will be able to provide a more complete picture of brain-behavior relationships in HD.

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