The efficacy of levodopa/carbidopa/entacapone on cognitive function in moderate to advanced Parkinson’s disease and its relationship with peripheral inflammatory cytokines

Entacapone has been widely used in the treatment of moderate to advanced Parkinson's disease (PD), and its efficacy for motor symptoms has been well-known from several clinical trials and long-term clinical use. The efficacy of Levodopa/Carbidopa/Entacapone (LCE) on neuropsychological functions in moderate to advanced PD has not been validated yet, and little is known about the effect of LCE on peripheral inflammatory cytokines. The aim of this study was to investigate the efficacy of LCE on neuropsychological functions in moderate to advanced PD and to explore its relationship with the changes in peripheral inflammatory cytokine levels. All patients were randomly assigned to the experimental group receiving treatment of LCE or the control group receiving treatment of Levodopa/Carbidopa (LC). All patients were clinically evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), the total score of the Parkinson's Disease Questionnaire-39 (PDQ-39), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD), and serum homocysteine (HCY) as well as serum inflammatory cytokines were measured at baseline and after 8 weeks. The moderate to advanced PD patients treated with LCE had more significant improvement in MMSE scores (P = 0.004) and MoCA scores (P = 0.001), as well as a greater decline in IL-6 levels (P = 0.002) than those treated with LC. There were no significant differences in the changes of the UPDRS III, PDQ39, HAMA, and HAMD scores between the two treatment groups. Linear correlation analysis revealed that there was a significant negative correlation between the improvement of MoCA scores (ΔMoCA) and the reduction of IL-6 levels (ΔIL-6) (correlation coefficient: -0.252; P = 0.024). The ability of LCE to improve cognitive function and to downregulate the peripheral inflammatory cytokine IL-6 levels in moderate to advanced PD is superior to the traditional dopamine preparation—LC. LCE may improve cognitive function by suppressing the levels of inflammatory cytokines like IL-6. The full name of the registry: Dongyang People's Hospital, Affiliated to Wenzhou Medical University. The trial registration number (TRN): ChiCTR2400091631. The date of registration: October 31, 2024 (Retrospectively registered).