Fig. 2: Annualized changes in volumetric measures longitudinally.

a–f, Putamen (a), caudate (b), gray matter (c), white matter (d), whole brain (e) and ventricles (f) are shown. For each structure, we present (i) comparison of standardized residuals (age- and sex-adjusted) for the annualized rate of change in HDGE (n = 54; red) and control (n = 34; gray) groups, (ii) comparison of standardized residuals for annualized rate of change within HDGE by follow-up HD-ISS stage 0 (orange) and stage 1 (green) and (iii) scatterplots of volume by CAP100 score, colored by HD-ISS stage within HDGE. Repeated visits per participant are connected by black lines, with baseline shown as squares and follow-up as circles. HD-ISS stages are represented as follows: stage 0 (orange), stage 1 (green) and stage 2 (blue). Negative standardized residuals denote a rate of change below the adjusted mean across groups. Each box plot displays the median (horizontal line), interquartile range (box) and whiskers extending to 1.5× IQR. Sample sizes (n) reflect biological replicates per group, with n = 54 for HDGE and n = 34 for controls; data represent longitudinal measures per participant, with no technical replicates. Volumetric change analyses for brain structures, excluding the putamen, used a single boundary-shift integral measure or voxel-based morphometry measure of scan pairs per participant (baseline to follow-up) converted to annual rates and modeled by ordinary least squares regression. Putamen changes were calculated by subtracting baseline MALP-EM segmentations from follow-up segmentations and dividing the result by the follow-up duration. Analysis results and residual adjustments reflect control for baseline age, sex and their interaction. Statistical two-sided group comparisons were adjusted for multiple comparisons using the FDR, with P values, degrees of freedom and confidence limits provided in Extended Data Table 2. CAP, CAG-Age Product; ICV, intracranial volume; IQR, interquartile range.