Subsegmentation of the caudate nucleus in prodromal Huntington’s disease reveals a rostro-caudal gradient of degeneration
Embargo Date
2028-02-15
OA Version
Citation
Abstract
Huntington’s Disease (HD) is a progressive inherited neurodegenerative disease caused by an autosomal dominant CAG trinucleotide repeat expansion in the Huntington gene. Atrophy of the caudate nucleus occurs prior to the onset of overt motor symptoms and is thought to progress in a caudal-to-rostral direction. This progression has not been systematically evaluated using modern high-resolution MRI analysis methods. The current study examined whether degeneration of the caudate is observed in a caudo-to-rostral pattern in prodromal HD. Structural MRIs were analyzed from 25 prodromal HD subjects and 23 healthy controls. The caudate, putamen, and nucleus accumbens were manually segmented based on a modified Harvard-Oxford Atlas parcellation framework. The caudate was subdivided into the head, body, and genu, and the putamen was subdivided into anterior, middle, and posterior regions. All segmentations were performed by raters blinded to the treatment group. Results showed the HD group had significantly smaller volumes of the caudate head bilaterally relative to control individuals. Additionally, the left but not the right caudate body exhibited a statistically significant volumetric decrease in HD subjects relative to controls. The volume of the tail was not statistically different between HD and controls. This pattern of volumetric loss was the same for raw values and for values corrected for head size differences. The putamen revealed volumetric loss was greatest in the anterior portion bilaterally, as well as significant changes in the posterior regions. The nucleus accumbens (both left and right) were significantly more atrophied when compared to healthy controls. Striatal volumes were positively correlated with an index combining CAG repeat length and aging and CAP scores. Brain volumes did not correlate with cognitive measures. These results reveal that the caudal region of the caudate and the putamen is largely spared in prodromal HD, suggesting that HD is associated with a rostro-to-caudal progression of degeneration in the basal ganglia. This pattern of degeneration has potential to enhance the understanding of HD neuropathology and serve as a more sensitive MRI-based biomarker to optimize clinical trial outcomes.
Description
2025