Background: Although health-related quality of life is key for patients with long-term neurodegenerative conditions, measuring this is less straightforward and complex in Huntington's disease (HD). Objectives: To refine and validate a fully patient-derived instrument, the Huntington's Disease health-related Quality of Life questionnaire (HDQoL), and to elucidate health domains that are meaningful to patients’ lived experience. Methods: Five-hundred forty-one participants, from premanifest to end-stage disease, completed the HDQoL, together with generic quality-of-life measures and in-person motor, cognitive, and behavioral assessments. The psychometric properties of the HDQoL were examined using factor analysis and Rasch analysis. Results: Four HDQoL domains emerged, reflecting the classical triad of HD features; they were Physical-Functional, Cognitive, and 2 different behavioral aspects, that is, the Mood-Self domain and a distinct Worries domain. These domains clarify the behavioral sequelae as experienced by patients, and all showed good to excellent internal consistency. Known-groups analyses illustrated significant and graded changes in clinical assessments and corresponding HDQoL domains across disease severity levels. Convergent and discriminant validity was demonstrated by the expected pattern of correlations between specific HDQoL domains and corresponding domain-relevant clinical assessments as well as patient-reported measures. The data demonstrate robust support for the refined HDQoL across disease stages. Conclusions: The HDQoL, with its 2 distinct behavioral domains of Mood-Self and Worries as well as the Physical-Functional and Cognitive domains, is a relevant, reliable, and valid patient-derived instrument to measure the impact of HD across all severity stages.
- Huntington's disease
- patient-reported outcome
- presymptomatic/preclinical Huntington's disease
- quality of life