Fig. 1: Longitudinal change in clinical, cognitive and neuropsychiatric measures.

a, The distribution of HD-ISS stages at baseline and at follow-up 4.5 years later. b, A probability matrix for being in each HD-ISS stage across different ages for individuals with a mean CAG repeat length of 42, which is comparable to the HD-YAS cohort. These probabilities are derived from data in the Enroll-HD, PREDICT-HD and TRACK-HD studies, which were used to develop the HD-ISS²⁶. The black dashed box highlights the HD-YAS cohort at baseline, while the red box indicates their position at follow-up after 4.5 years. c, A radar plot showing group differences in longitudinal changes in cognitive measures. d, A radar plot showing group differences in longitudinal changes for neuropsychiatric and functional measures. The black line represents the standardized mean difference between the HDGE and control groups, with conventional frequentist 95% CI shaded in gray. The red circle denotes no difference between means; values within this circle indicate greater change over time in the HDGE group. After FDR correction for multiple comparisons, there were no significant longitudinal group differences in any cognitive or neuropsychiatric measures. Further details on longitudinal changes in cognitive measures can be found in Supplementary Table 1 and neuropsychiatric measures in Supplementary Table 2. Cross-sectional changes in cognitive measures are presented in Supplementary Table 3 and neuropsychiatric changes in Supplementary Table 4. Cross-sectional findings are visualized in Supplementary Fig. 1. AMI, Apathy Motivation Index; BIS, Barratt Impulsivity Scale; CI, confidence interval; ED, extra dimensional; FSBS, Frontal Systems Behavioral Scale; IED, intra–extra-dimensional set shifting; OCI, Obsessive-Compulsive Inventory; OTS, One Touch Stockings; PAL, paired associates learning; PSQI, Pittsburgh Sleep Quality Index; RVP, rapid visual processing; RVP A’, a signal detection theory measure of target sensitivity and mean response latency; SDMT, Symbol Digit Modalities Test; SF-36, 36-item self-report survey; SSRT, stop-signal reaction time; SSTAI, Speilberger State-Trait Anxiety Inventory; SWM, spatial working memory; ZSDS, Zung Self-rating Depression Score.