OBJECTIVES: Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder that leads to progressive loss of functional capacity. This retrospective, registry-based study assessed the associations between HD functional endpoints measured by the Unified HD Rating Scale (UHDRS) Total Functional Score (TFC) and other scales (Total Motor Score [TMS] , Verbal Fluency Test [VFT], Problem Behavior Assessment [PBA]-Apathy), and quality-of-life outcomes (QoL) measured by Short-Form Survey 12 (SF-12) and other QoL scales (Euro-QoL-5D [EQ-5D], Work Productivity and Activity Impairment-Overall Work Impairment due to HD [WPAI-OWIHD]) in HD gene carriers.

METHODS: Data on functional endpoints and QoL outcomes from HD gene carriers were retrieved from the Enroll-HD global registry. Adult HD patients (≥18 years) with a positive HD genetic test and having ≥1 on-site visit with TFC assessment were analysed. The association between functional endpoints and QoL outcomes were assessed using descriptive analysis, inferential statistics including but not limited to distribution of endpoints, and linear mixed models. Other baseline characteristics analysed were age, gender, Charlson comorbidity index, and visit number.

RESULTS: Overall, 11,553 HD gene carriers were analysed. Of these, 8,387 (73%) had manifest HD and the remaining 3,544 (27%) had pre-manifest status. Among manifest HD patients, TFC contributes significantly to the model while deriving SF-12 PCS (Physical Component Summary) score (coefficient: 0.8222; 95% confidence interval [CI]: 0.6945, 0.9498; p<0.001) and SF-12 MCS (Mental Component Summary) score (coefficient: 0.4898; 95% CI: 0.3165, 0.6630; p<0.001). Further, age and gender contributed significantly to both the models (p<0.05). The association of TFC with SF-12 derived EQ-5D and WPAI-OWIHD was found to be significant (both p<0.001).

CONCLUSIONS: TFC was found to have statistically significant and seemingly linear relationship with SF-12 (PCS, MCS) and other QoL outcomes (EQ-5D, and WPAI-OWIHD) among manifest HD patients suggesting that TFC can be used as a proxy of QoL.