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Background: Cognitive decline may occur in patients with end-stage renal disease (ESRD), and is particularly severe in patients with ESRD undergoing hemodialysis; however, the mechanism of this relationship between cognitive decline and ESRD is unclear. Cortical-based structural and functional analysis can be used to understand these cortical changes and their relationship with cognitive decline in non-dialysis and maintenance dialysis ESRD patients. This study aimed to examine whether there was any correlation between alterations in cortical and resting-state function changes and cognitive decline in patients diagnosed with ESRD., Methods: The study included a total of 126 participants who underwent laboratory assessments, neuropsychological tests, and brain magnetic resonance imaging (MRI). Of the 126 patients, 40 were ESRD without hemodialysis (ESRD-ND) patients, 40 were ESRD with hemodialysis (ESRD-HD) patients, and 46 were healthy controls (HCs)., Results: In terms of the cortical changes, the thickness and volume of the left medial temporal cortex were smaller in the ESRD-ND group than in the HC group. The thickness and volume of the double medial temporal cortex were reduced in the ESRD-HD group compared to the ESRD-ND group. The cortical volume in the anterior cingulate and medial prefrontal cortex (AntCing&#95;MedPFC) was reduced in ESRD-HD group compared to both the ESRD-ND and HC groups. In terms of the functional changes, the regional homogeneity (ReHo) of the double medial temporal cortex was higher in the ESRD-HD group than in the ESRD-ND group, and higher in the ESRD-ND group than in the HC group. The ReHo of the AntCing&#95;MedPFC was higher in both the ESRD-HD and ESRD-ND groups than in the HC group. The correlation analysis after covariation-correction showed that the cortical thickness (r=0.360, P=0.026) and cortical volume (r=0.440, P=0.006) of the medial temporal lobe in the ESRD-HD group were positively correlated with the Montreal Cognitive Assessment (MoCA) score. The cortical thickness (r=0.571, P<0.001) and cortical volume (r=0.529, P=0.001) of the posterior cingulated gyrus were positively correlated with the MoCA score in the ESRD-ND group., Conclusions: Our findings suggest that ESRD patients undergo more cognitively related cortical structural and functional changes than HCs. Dialysis can aggravate or cause changes in new brain regions. Changes in the cortex and volume of the posterior cingulate gyrus in ESRD patients is an important cause of cognitive decline. Damage to the medial temporal lobe by dialysis exacerbates this trend., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1265/coif). B.X. is an employee of MR Research, GE Healthcare, Beijing, China. The other authors have no conflicts of interest to declare., (2025 AME Publishing Company. All rights reserved.)