Objective: To investigate the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and deterioration of global and specific domains of cognitive function in peritoneal dialysis (PD) patients.Methods: This was a multi-center prospective cohort study. The PD patients who met the inclusion criteria were examined with general and specific cognitive function between March 2013 and November 2013. The patients were divided into MIA0, MIA1 and MIA2 groups, according to items of “Yes” for whether or not having cardiovascular disease, serum albumin≤35 g/L or high-sensitive C-reactive protein (hs-CRP) ≥3 mg/L. After 2 years, the patients maintained on PD would be repeatedly measured with cognitive function. The Chi-square test, One-way ANOVA, Kruskal-wallis H rank sum test were used to compare the differences of clinical characteristics, biochemical data, and global and specific cognitive function parameters among the three groups at baseline, and two years later, respectively. The Bonferroni method was applied to adjust the significance level for further comparison between each two different groups. The change of score in each cognitive parameter of global and specific domains was used as dependent variable. Age, gender, education level, depression index, body-mass index, diabetes mellitus, serum sodium levels and MIA (MIA0 was control, MIA1 and MIA2 as dummy variables) were all included in the multivariable linear regression models to analyze the risk factors of the deterioration of cognitive function. The analysis for each cognitive domain was adjusted for the baseline score of the corresponding cognitive parameter. All the analyses were performed using SPSS for Windows, software version 25.0 (SPSS Inc., Chicago, IL). Results: Over two-year follow up, the prevalence of cognitive impairment increased from 20.0% to 24.7%, absolute decrease of 3MS scores were more significantly decreased in MIA2 (-3.9±12.0 vs. 1.1±6.7, P<0.01) and MIA1 group (-2.3±11.8 vs. 1.1±6.7, P<0.05) than those in MIA0 group respectively. Specific cognitive functions, included executive function (trail-making tests A and B, P=0.401,P=0.176), immediate memory (P=0.437), delayed memory (P=0.104), visuospatial skill (P=0.496), and language ability (P=0.171) remained unchanged. Advanced age, lower education, diabetes mellitus and depression were all correlated with the deterioration of one or more cognitive domains, and the patients having one item of MIA syndrome were prone to develop the deterioration of 3MS (P=0.022). Furthermore, the patients having two or more items of MIA syndrome were more likely to develop the deterioration of not only 3MS (P <0.001), but also delayed memory, visuospatial skill, and language ability (P=0.002, P=0.007, P=0.004, respectively).Conclusion: Patients with one item or above of MIA syndrome were at high-risk for the deterioration of global cognitive function. The more MIA syndrome items there were, the more specific cognitive domains deteriorated.