Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington’s disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and while the CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in HD using a novel longitudinal MRI analysis; our hypothesis was that the rate of brain atrophy is influenced by the age of onset of HD.

We scanned 22 patients with HD at approximately one-year intervals; individuals were divided into one of three groups, determined by the relative age of onset.

We found significant differences in the rates of atrophy of cortex, white matter and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy as compared to those who developed symptoms during middle-age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensori-motor, posterior frontal and portions of parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. While both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions.

Rates of regional brain atrophy are influenced the age of onset of HD symptoms and are only partially explained by the CAG repeat length. These findings suggest that other genetic, epigenetic and environmental factors play important roles in neurodegeneration in HD.