Cytokines and Changes in Cognitive Function in Patients on Hemodialysis: A Three-Year Follow-Up Cohort Study

Background: Patients on maintenance hemodialysis (HD) exhibit a higher burden of global cognitive impairment and hypomnesia compared to individuals of the same age in the general population. These dialysis patients often suffer from chronic inflammation. However, few studies have explored the association between cytokines and cognitive function in this population. Methods: A total of 166 HD patients were enrolled in this longitudinal study. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scores, evaluating memory, executive function, visual-spatial skills, language, attention, and orientation. Plasma levels of cytokines (interleukin IL-4, IL-6, IL-8, IL-10, and Tumor Necrosis Factor α) were measured by flow cytometry. The association between changes in cognitive function and cytokine levels was analyzed using generalized estimating equation models. Results: Among the 166 dialysis patients, the average age was 49.9 (±11.2) years, with 102 (61.4%) being male. The mean levels of IL-4, IL-6, IL-8, IL-10, and TNFα were 0.6 pg/ml, 7.7 pg/ml, 17.2 pg/ml, 1.9 pg/ml, and 0.8 pg/ml, respectively. After 3 years, 133 patients participated in the follow-up. Compared to baseline, follow-up patients showed higher scores in the executive dimension but lower scores in the visual-spatial and orientation dimensions. After adjusting for potential confounders, the anti-inflammatory cytokines IL-4 and IL-8 were protective predictors of increased executive function scores. Conversely, the pro-inflammatory factor TNFα was an independent risk factor for decreased orientation scores. Additionally, pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-4 were associated with decreased visual-spatial scores. Principal component analysis demonstrated that plasma levels of IL-4, IL-8, and IL-6 explained 35.6%, 23.2%, and 12.6% of the variance in cognitive function changes, respectively. Conclusion: Cytokines serve as independent predictors of cognitive function changes in dialysis patients. Funding: Government Support – Non-U.S.