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      Associations between small and middle molecules clearance and the change of cognitive function in peritoneal dialysis

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          Abstract

          Background

          Uremic toxins have been suspected as potential contributors for cognitive impairment in peritoneal dialysis (PD) patients. However, associations between the clearance of serum small and middle molecules and the change of cognitive function were not fully explored and then we explored this issue in the present study.

          Method

          A total of clinically-stable 222 patients on PD were enrolled and then followed up for 2 years in this single-center prospective cohort study. Small and middle molecules clearances were examined by urea clearance (Kt/V), creatinine clearance (Ccr) and beta-2 microglobulin (B2M) clearance via dialysate and urine at baseline and after 2 years. Global and specific cognitive impairment were measured at baseline and after 2 years. Modified Mini-Mental State Examination (3MS) was assessed for global cognitive function, trail-making tests A and B for executive function and subtests of the battery for the assessment of neuropsychological status for immediate and delayed memory, visuospatial skills and language ability.

          Results

          The median of total Kt/V, Ccr and B2M clearance were 1.89, 53.2 l/w/1.73 m 2 and 17.5 l/w/1.73 m 2, respectively at baseline. The prevalence of global cognitive impairment was 12.3% for 222 patients and 15.4% for the remained 130 patients after 2 years. At baseline, total Kt/V was independently positively associated with delayed memory function. Total and dialysate beta-2 microglobulin clearance was positively associated with 3MS scores and negatively with completion time on trail A after multivariate adjustment. At 2 years, we observed a significant difference in the changing trend of 3MS scores between groups divided by total B2M clearance ( P = 0.033), which still maintained to be meaningful after multivariate adjustment ( P = 0.024). Patients with total B2M clearance > 19.0 l/w/1.73 m 2 got significant improvement on their 3MS scores ( P = 0.005). Patients divided by total Kt/V or Ccr were not significantly different in the trends of general and any specific cognitive function during the follow up.

          Conclusion

          The higher middle molecules clearance independently correlated to better performance on general cognitive and executive function in PD patients, which also predict an improvement in general cognitive function during the follow up.

          Electronic supplementary material

          The online version of this article (10.1007/s40620-019-00661-8) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          The Modified Mini-Mental State (3MS) examination.

          E Teng, H Chui (1987)
          The Mini-Mental State (MMS) examination is a widely used screening test for dementia. The Modified Mini-Mental State (3MS) incorporates four added test items, more graded scoring, and some other minor changes. These modifications are designed to sample a broader variety of cognitive functions, cover a wider range of difficulty levels, and enhance the reliability and the validity of the scores. The 3MS retains the brevity, ease of administration, and objective scoring of the MMS but broadens the range of scores from 0-30 to 0-100. Greater sensitivities of the 3MS over the MMS are demonstrated with the pentagon item drawn by 249 patients. A summary form for administration and scoring that can generate both the MMS and the 3MS scores is provided so that the examiner can maintain continuity with existing data and can obtain a more informative assessment.
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            Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study.

            Cerebral white matter lesions are a common finding on MRI in elderly persons. We studied the prevalence of white matter lesions and their relation with classic cardiovascular risk factors, thrombogenic factors, and cognitive function in an age- and gender-stratified random sample from the general population that consisted of 111 subjects 65 to 84 years of age. Overall, 27% of subjects had white matter lesions. The prevalence and severity of lesions increased with age. A history of stroke or myocardial infarction, factor VIIc activity, and fibrinogen level were each significantly and independently associated with the presence of white matter lesions. Significant relations with blood pressure level, hypertension, and plasma cholesterol were present only for subjects aged 65 to 74 years. White matter lesions tended to be associated with lower scores on tests of cognitive function and were significantly associated with subjective mental decline. This study suggests that classic cardiovascular risk factors, as well as thrombogenic factors, are associated with white matter lesions in subjects over 65 years of age in the general population, and that these lesions may be related to cognitive function.
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              Chronic Kidney Disease and Cognitive Impairment: A Systematic Review and Meta-Analysis

              Background: Chronic kidney disease (CKD) has emerged as a possible new risk factor of cognitive impairment and dementia, but results of studies remain conflicting. Methods: A systematic literature research of electronic databases (MEDLINE, Cochrane Library and Goggle Scholar covering the period from 1980 to January 2012) and meta-analysis of relevant cross-sectional and longitudinal studies were conducted to assess the association of CKD and cognitive decline. Results: Most cross-sectional and longitudinal studies suggest an association between cognitive impairment and CKD. Meta-analysis of cross-sectional and longitudinal studies comprising 54,779 participants yielded an association of cognitive decline in patients with CKD compared with patients without CKD (OR 1.65, 95% CI 1.32–2.05; p < 0.001, and OR 1.39, 95% CI 1.15–1.68; p < 0.001, respectively). Conclusion: This is the first meta-analysis assessing the impact of CKD on cognitive decline. Our results suggest CKD being a significant and independent somatic risk factor in the development of cognitive decline.
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                Author and article information

                Contributors
                jie.dong@bjmu.edu.cn
                Journal
                J Nephrol
                J. Nephrol
                Journal of Nephrology
                Springer International Publishing (Cham )
                1121-8428
                1724-6059
                23 October 2019
                23 October 2019
                2020
                : 33
                : 4
                : 839-848
                Affiliations
                [1 ]Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education, Beijing, 100034 China
                [2 ]GRID grid.417298.1, ISNI 0000 0004 1762 4928, Renal Division, , Xinqiao Hospital, Army Medical University, ; Chongqing, China
                [3 ]GRID grid.411472.5, ISNI 0000 0004 1764 1621, Emergency Department, , Peking University First Hospital, ; Beijing, China
                Author information
                http://orcid.org/0000-0001-7298-3307
                Article
                661
                10.1007/s40620-019-00661-8
                7381472
                31643008
                1c33ef46-612d-42ff-b98f-ec5a980e323f
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 18 June 2019
                : 3 October 2019
                Categories
                Original Article
                Custom metadata
                © Italian Society of Nephrology 2020

                peritoneal dialysis,urea,creatinine,beta-2 microglobulin,solute,clearance,cognitive function,executive function

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