Determinants of caregiver burden in advanced Parkinson’s disease: a multidimensional and sex-sensitive perspective

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder whose advanced stages (Hoehn & Yahr IV-V) place significant demands on informal caregivers, leading to multidimensional burden. Although functional and cognitive decline contribute to caregiver strain, the influence of sex and sex differences remains poorly understood. Objectives: This study examined the relationship between patients' clinical characteristics and caregiver burden, and explored sex-based differences to identify sex-sensitive patterns. Methods: Thirty-eight individuals with advanced PD and their primary caregivers were assessed. Patients underwent clinical and neuropsychological evaluation using the Mini Mental State Examination (MMSE), Hamilton Rating Scales for Anxiety and Depression, Pittsburgh Sleep Quality Index (PSQI), Parkinson's Disease Questionnaire (PDQ-39), and Activities of Daily Living (ADL/IADL) scales. Caregiver burden was measured with the Caregiver Burden Inventory (CBI). Associations were tested using Spearman's rank correlations with false discovery rate correction, and analyses were stratified by patient sex. Results: Reduced patient autonomy was strongly associated with higher caregiver burden across emotional, physical, and time-dependent domains. Poorer quality of life, particularly mobility and bodily discomfort, further predicted caregiver strain. Female patients showed higher anxiety, but these symptoms were less related to caregiver burden. In contrast, functional and neuropsychiatric decline in male patients was more strongly linked to caregiver burden. Cognitive impairment was associated with increased caregiving time and demands. Female caregivers reported stronger links between patient dependence and burden. Conclusion: Functional decline, cognitive impairment, and reduced QoL in advanced PD significantly increase caregiver burden, with sex influencing these relationships. Sex-sensitive, multidisciplinary interventions are needed.