BACKGROUND: Caregiver burden in Parkinson's disease (PD) is influenced by both motor and non-motor symptoms; however, the relative contribution of these domains in late-stage PD remains unclear. This study aimed to examine the clinical determinants of caregiver burden and to explore whether motor-functional impairment plays a relevant role in advanced PD. METHODS: Thirty patient-caregiver dyads were enrolled. Individuals with late-stage PD (Hoehn and Yahr stage IV) underwent a comprehensive clinical evaluation assessing motor performance, cognitive functioning and functional autonomy. Caregiver burden was assessed using a multidimensional self-report questionnaire. Associations were analyzed using Spearman correlations with false discovery rate correction. Multivariable linear regression models were fitted to explore independent contributors across motor, sleep, and QoL domains. RESULTS: Caregiver burden was associated with longer caregiving duration (ρ = 0.81, p_FDR < 0.001), reduced functional autonomy (IADL: ρ = -0.76; ADL: ρ = -0.63; both p_FDR < 0.001), and poorer motor performance (ρ = -0.67, p_FDR < 0.001). Among non-motor domains, burden correlated with worse mobility-related QoL (ρ = 0.68, p_FDR < 0.001) and sleep disturbance (ρ = 0.57, p_FDR = 0.003), whereas cognition and affective symptoms were not significantly associated after correction. The motor-focused regression model showed slightly higher explanatory power (R² = 0.80). CONCLUSIONS: In advanced PD, caregiver burden is driven by motor-functional dependence and loss of autonomy, with sleep disturbance and perceived mobility-related impairment further contributing. These findings underscore the role of motor-functional disability in shaping caregiver strain in late-stage disease, highlighting the need for integrated, caregiver-centered management strategies. BACKGROUND: Caregiver burden in Parkinson's disease (PD) is influenced by both motor and non-motor symptoms; however, the relative contribution of these domains in late-stage PD remains unclear. This study aimed to examine the clinical determinants of caregiver burden and to explore whether motor-functional impairment plays a relevant role in advanced PD. METHODS: Thirty patient-caregiver dyads were enrolled. Individuals with late-stage PD (Hoehn and Yahr stage IV) underwent a comprehensive clinical evaluation assessing motor performance, cognitive functioning and functional autonomy. Caregiver burden was assessed using a multidimensional self-report questionnaire. Associations were analyzed using Spearman correlations with false discovery rate correction. Multivariable linear regression models were fitted to explore independent contributors across motor, sleep, and QoL domains. RESULTS: Caregiver burden was associated with longer caregiving duration (ρ = 0.81, p_FDR < 0.001), reduced functional autonomy (IADL: ρ = -0.76; ADL: ρ = -0.63; both p_FDR < 0.001), and poorer motor performance (ρ = -0.67, p_FDR < 0.001). Among non-motor domains, burden correlated with worse mobility-related QoL (ρ = 0.68, p_FDR < 0.001) and sleep disturbance (ρ = 0.57, p_FDR = 0.003), whereas cognition and affective symptoms were not significantly associated after correction. The motor-focused regression model showed slightly higher explanatory power (R² = 0.80). CONCLUSIONS: In advanced PD, caregiver burden is driven by motor-functional dependence and loss of autonomy, with sleep disturbance and perceived mobility-related impairment further contributing. These findings underscore the role of motor-functional disability in shaping caregiver strain in late-stage disease, highlighting the need for integrated, caregiver-centered management strategies.