Year: 2010
Type: article
Study design: Observational Study
Abstract: BACKGROUND: In Huntington disease (HD), substantial striatal atrophy precedes clinical motor symptoms. Accordingly, neuroprotection should prevent major cell loss before such symptoms arise. To evaluate neuroprotection, biomarkers such as MRI measures are needed. This requires first establishing the best imaging approach. METHODS: Using a cross-sectional design, we acquired T1-weighted and diffusion-weighted scans in 39 preclinical (pre-HD) individuals and 25 age-matched controls. T1-weighted scans were analyzed with gross whole-brain segmentation and voxel-based morphometry. Analysis of diffusion-weighted scans used skeleton-based tractography. For all imaging measures, we compared pre-HD and control groups and within the pre-HD group we examined correlations with estimated years to clinical onset. RESULTS: Pre-HD individuals had lower gross gray matter (GM) and white matter (WM) volume. Voxel-wise analysis demonstrated local GM volume loss, most notably in regions consistent with basal ganglia-thalamocortical pathways. By contrast, pre-HD individuals showed widespread reductions in WM integrity, probably due to a loss of axonal barriers. Both GM and WM imaging measures correlated with estimated years to onset. CONCLUSIONS: Using automated, observer-independent methods, we found that GM loss in pre-HD was regionally specific, while WM deterioration was much more general and probably the result of demyelination rather then axonal degeneration. These findings provide important information about the nature, relative staging, and topographic specificity of brain changes in pre-HD and suggest that combining GM and WM imaging may be the best biomarker approach. The empirically derived group difference images from this study are provided as regions-of-interest masks for improved sensitivity in future longitudinal studies.
Source: Neurology
Institution: University of California San Diego
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, CHDI Foundation, University of Rochester, National Alliance for Research on Schizophrenia and Depression, Elan, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke
Awards: Imaging Studies in Neurotoxicity and Neurodevelopment, How inhibitory control prevents thought intrusions and sensory and motor provocations, Evaluating a Fronto-Basal-Ganglia White-Matter Network for Behavioral Stopping in Lesion Patients, Biomarkers of Autism at 12 months: From Brain Overgrowth to Genes, G879329325
OpenAlex ID: W2101354696