Journal
MOVEMENT DISORDERS
Volume 26, Issue 14, Pages 2544-2551Publisher
WILEY-BLACKWELL
DOI: 10.1002/mds.23912
Keywords
Huntington's disease; prodromal HD; longitudinal atrophy; volumetric MRI; MRI biomarkers
Categories
Funding
- CHDI Foundation
- CHDI
- NeuroSearch
- Elan Corporation
- University of Rochester
- Alzheimer's Disease Cooperative Study
- Huntington's Study Group
- Medivation, Inc.
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Future clinical trials of neuroprotection in prodromal Huntington's (known as preHD) will require sensitive in vivo imaging biomarkers to track disease progression over the shortest period. Since basal ganglia atrophy is the most prominent structural characteristic of Huntington's pathology, systematic assessment of longitudinal subcortical atrophy holds great potential for future biomarker development. We studied 36 preHD and 22 age-matched controls using a novel method to quantify regional change from T1-weighted structural images acquired 1 year apart. We assessed cross-sectional volume differences and longitudinal volumetric change in 7 subcortical structuresthe accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. At baseline, accumbens, caudate, pallidum, and putamen volumes were reduced in preHD versus controls (all P < .01). Longitudinally, atrophy was greater in preHD than controls in the caudate, pallidum, and putamen (all P < .01). Each structure showed a large between-group effect size, especially the pallidum where Cohen's d was 1.21. Using pallidal atrophy as a biomarker, we estimate that a hypothetical 1-year neuroprotection study would require only 35 preHD per arm to detect a 50% slowing in atrophy and only 138 preHD per arm to detect a 25% slowing in atrophy. The effect sizes calculated for preHD basal ganglia atrophy over 1 year are some of the largest reported to date. Consequently, this translates to strikingly small sample size estimates that will greatly facilitate any future neuroprotection study. This underscores the utility of this automatic image segmentation and longitudinal nonlinear registration method for upcoming studies of preHD and other neurodegenerative disorders. (c) 2011 Movement Disorder Society
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