Nonmotor fluctuations in Parkinson's disease: impact on caregiving and quality of life

Background: Parkinson’s disease (PD) is characterized by a combination of motor and non-motor symptoms, which can fluctuate over time. Recognition of nonmotor fluctuations (NMF) as a distinct and relevant feature of PD is recent, and their impact on patients' health-related quality of life (HRQoL) and on caregivers' burden remains underexplored. This study aimed to evaluate the effect of NMF on patients’ HRQoL and caregiver burden, and to compare it with the impact of motor complications (MC). Methods: Patients and caregivers were consecutively recruited from five Italian Movement Disorder centers. Assessments included the Non-Motor Fluctuation Assessment, the MDS-sponsored Unified PD Rating Scale, the Mini-Mental State Examination, the 39-item Parkinson’s Disease Questionnaire (PDQ-39), and the Zarit Burden Interview (ZBI). Linear regression analyses examined associations between total NMF and MC scores with PDQ-39 and ZBI. Logistic regression estimated the odds of moderate-severe caregiver burden based on NMF. Results: 149 patients and 135 caregivers were included. Higher NMF scores were associated with worse HRQoL (PDQ-39: Beta = 0.318; p < 0.001), and correlated with most PDQ-39 domains, excluding stigma. MC also correlated with PDQ-39-(Beta = 0.338; p < 0.001), particularly in domains such as mobility, ADLs, communication, and bodily discomfort. Both NMF and MC scores were associated with caregiver burden (ZBI: Beta = 0.374 and 0.437, respectively; p < 0.001). Each additional NMF point increased the odds of caregiver burden by 11.6% (OR = 1.116, 95% CI:1.043–1.194, p < 0.001). Conclusions: NMF significantly affect both patient HRQoL and caregiver burden, with an impact comparable to that of MC. Systematic assessment and targeted interventions for NMF should be integrated into routine PD care.