Association of Klotho with cognitive impairment and sleep difficulties: a multicenter cross-sectional study

Abstract Aims This study aimed to examine the clinical profile of maintenance hemodialysis (MHD) patients, investigate the prevalence of cognitive impairment (CI) and sleep difficulties (SD), and explore their associations with factors such as α-Klotho and β-Klotho. Methods Patients were recruited via convenience sampling from three hemodialysis centers in Shihezi City between April 2023 and April 2024, all of whom were receiving hemodialysis treatment. Data collected included patients’s characteristics, conditions of CI, conditions of SD, and serological indicators.Influencing factors were analyzed using logistic regression analysis. The predictive value of these influencing factors for CI and SD was verified via the receiver operating characteristic (ROC) curve. Themediating effect between the common influencing factors of CI and SD was analyzed through simple mediation analysis. Results A total of 281 MHD patients were surveyed. Among them, 181 patients were identified with cognitive impairment (CI), yielding a prevalence rate of 64.41%; 138 MHD patients had sleep difficulties (SD) or suspected sleep difficulties, accounting for 49.11% of the total cohort. Multivariate logistic regression analysis revealed that age and the Athens Insomnia Scale-8 (AIS-8) score were negatively associated with cognitive impairment in MHD patients (P < 0.05), while α-Klotho, β-Klotho, and years of education were positively associated with cognitive impairment (P < 0.05). Additionally, α-Klotho showed a negative correlation with SD or suspected SD in MHD patients (P < 0.05). Mediation effect analysis indicated that SD mediated 8.35% of the association between α-Klotho and CI. Conclusion Age, AIS-8 score, years of education, α-Klotho, and β-Klotho are associated with cognitive impairment (CI) in MHD patients. Among these factors, α-Klotho is negatively correlated with both CI and sleep difficulties (SD) and may influence the occurrence of CI by mediating SD. Thus, α-Klotho could serve as an important indicator for predicting cognitive impairment in MHD patients.