Remote smartphone-based spoken language screening predicts clinical markers in Huntington’s disease

Assessment and monitoring of Huntington's disease (HD) symptoms remain limited to infrequent, clinic-based evaluations. We evaluated whether fully automated linguistic analysis of speech tasks recorded via smartphone can remotely capture core clinical markers of HD severity. In this cross-sectional multicenter study across Czech and German sites, 53 participants, including 30 HD (9 pre-symptomatic, 3 prodromal, and 18 manifest) and 23 healthy controls, completed a smartphone-based speech assessment, including spontaneous monologue and fairy tale retelling for 7 consecutive days. Recordings were automatically transcribed and analyzed using natural language processing to derive 3 lexical and 3 syntactic features. Predictive models for clinical outcomes based on the Unified Huntington's Disease Rating Scale and cognitive scales were built using multivariate linear regression with cross-validation. Linguistic features predicted HD severity across multiple domains with high predictive performance, explaining up to 57% of the variance in cognitive performance, 63% in motor impairment, and 59% in functional capacity. A median of 6 days for monologue and 3 for retelling was sufficient to reach 90% of maximal predictive performance. Compared to controls, HD participants showed reduced vocabulary range and increased phrase repetition in both tasks (p < 0.05), with additional monologue-specific deficits in sentence length (p = 0.018) and syntactic complexity (p = 0.004). Fully automated analysis of smartphone-based language assessment can remotely quantify cognitive, motor, and functional impairment in HD, offering a scalable, low-burden digital biomarker for clinical trials and decentralized monitoring.