This project will utilize neuroimaging techniques to identify brain abnormalities in persons at risk for Huntington's disease (HD).
The specific aims i nclude: Documentation of the earliest neuroimaging evidence of HD cross-sectionally in persons who have been identified through DNA testing as having the linked genetic marker, and therefore very likely having the gene; evaluation of structural changes in the brain (particularly the putamen) using magnetic resonance imaging (MRI); evaluation of regional cerebral blood flow (rCBF) changes in the cerebral cortex and basal ganglia using single photon emission computed tomography (SPECT); correlation of neuroimaging results with assessment of cognitive, emotional, and motor impairment. Subjects will be followed longitudinally to assess progression or emergence of neuroimaging changes relative to progression or emergence of clinical symptoms. There have been no prior quantitative SPECT or volumetric MRI studies in persons at risk for Huntington's disease, nor has any prior study tracked the emergence and progression of neuroimaging and clinical abnormalities in subjects with informative genetic tests for HD. Subjects will be participants in the Johns Hopkins program of predictive testing for Huntington's disease. At-risk subjects who have informative genetic testing results (probability > 95% for HD gene) will be asked to participate in the neuroimaging study. Gene-marker negative (probability < 5%) subjects will be used as controls. Groups will be matched for age, sex, race, education and socio-economic status. Marker-positive subjects will receive one SPECT scan and one MRI scan each year for five years. Marker-negative controls will receive 2 scan pairs in five years. MRI scans will be quantitatively measured for caudate and putamen volumes, bicaudate ratio, whole brain volume and cerebro-spinal fluid volume. SPECT scans will be rated for regional cortical and subcortical rCBF values. Neurologic and neuropsychological tests will be given at least annually, and results will be correlated with neuroimaging changes.
| Harris, G J; Codori, A M; Lewis, R F et al. (1999) Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease. Brain 122 ( Pt 9):1667-78 |
| Aylward, E H; Codori, A M; Barta, P E et al. (1996) Basal ganglia volume and proximity to onset in presymptomatic Huntington disease. Arch Neurol 53:1293-6 |
| Harris, G J; Aylward, E H; Peyser, C E et al. (1996) Single photon emission computed tomographic blood flow and magnetic resonance volume imaging of basal ganglia in Huntington's disease. Arch Neurol 53:316-24 |
