Abstract
BACKGROUND: Huntington's disease (HD) leads to increasing dependence. Unlike psychiatric disorders, motor and cognitive deficits evolve progressively over time. Understanding their specific impact on daily activities is crucial for preserving autonomy. However, because cognitive tasks in HD rely on motor functions, and motor tasks demand cognitive processing, disentangling their specific impact remains a challenge. OBJECTIVE: To identify the specific contribution of cognitive and motor impairments on global functional capacity, basic and instrumental activities of daily living (ADL/IADL), and work-related activities (WRA) in HD. METHODS: 158 HD mutation carriers, enrolled in the BioHD (NCT01412125) and RepairHD (NCT03119246) studies, were evaluated with the Unified Huntington's Disease Rating Scale and the SelfCog. The SelfCog assesses motor processing separately from memory, language, executive functions and visuospatial processing. Linear regressions were fitted to assess how functional capacity declined with motor and cognition impairments. Odds of dependence in ADLs, IADLs and WRAs were estimated using logistic regressions. RESULTS: Cognitive and motor performance were independently associated with functional capacities, though motor performance showed a stronger association than cognitive performance. Decline of all SelfCog cognitive domains contributed to functional decline, with stronger association with global and executive scores compared to language, visuospatial, and memory domains. Higher global and executive deficits were associated with an increased risk of dependence in ADLs, IADLs, and WRAs. CONCLUSION: The independent contributions of motor, followed by cognitive-mainly executive-functions to functional decline suggest targeted interventions to preserve autonomy and quality of life in HD.