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Association of cardiovascular structure and function with cerebrovascular changes and cognitive function in older patients with end-stage renal disease.

ABSTRACT: The Dutch prospective multicenter cohort study COPE (Cognitive decline in Older Patients with End stage renal disease) aimed to investigate the association of cardiovascular structure and function with cerebrovascular changes and cognitive function in 85 older patients with chronic kidney disease stage 4 and 5, awaiting either dialysis or conservative care. MRI was performed measuring aortic stiffness (pulse wave velocity [PWV]) and cardiac systolic function (ejection fraction and cardiac index). Outcomes were MRI-derived cerebrovascular changes (microbleeds, lacunes and white matter hyperintensities) and cognitive function (memory, executive function and psychomotor speed). Mean age was 76 years and 66% were male. No statistically significant associations were observed between cardiovascular parameters and cerebrovascular changes. Cognitive function was worse in patients with high compared to low PWV in all three cognitive domains. Although there were clinically relevant associations of high PWV with poor cognition in all domains, after adjustment for age, sex and education only the Trail Making Test A remained statistically significant (p=0.030). In conclusion, this study suggests that a higher PWV might be associated with lower cognitive function, suggesting that arterial stiffness may be an underlying mechanism of development of cognitive impairment in older patients with ESRD. Larger studies should replicate and extend these findings.

SUBMITTER: Zijlstra LE

PROVIDER: S-EPMC7053617 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association of cardiovascular structure and function with cerebrovascular changes and cognitive function in older patients with end-stage renal disease.

Zijlstra Laurien E LE Trompet Stella S Jukema J Wouter JW Kroft Lucia J M LJM de Bresser Jeroen J van Osch Matthias J P MJP Hammer Sebastiaan S Witjes Marie-Noëlle MN van Buren Marjolijn M Mooijaart Simon P SP

Aging 20200107 2

The Dutch prospective multicenter cohort study COPE (Cognitive decline in Older Patients with End stage renal disease) aimed to investigate the association of cardiovascular structure and function with cerebrovascular changes and cognitive function in 85 older patients with chronic kidney disease stage 4 and 5, awaiting either dialysis or conservative care. MRI was performed measuring aortic stiffness (pulse wave velocity [PWV]) and cardiac systolic function (ejection fraction and cardiac index) ...[more]

PMID: 31907337

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Project description:Background: Functional connectivity detected by resting-state functional MRI (R-fMRI) helps to discover the subtle changes in brain activities. Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have impaired brain networks. However, the functional changes of brain networks in patients with ESRD undergoing peritoneal dialysis (PD) have not been fully delineated, especially among those with preserved cognitive function. Therefore, it is worth knowing about the brain functional connectivity in patients with PD by using R-fMRI. Methods: This case-control study prospectively enrolled 19 patients with ESRD receiving PD and 24 age- and sex- matched controls. All participants without a history of cognitive decline received mini-mental status examination (MMSE) and brain 3-T R-fMRI. Comprehensive R-fMRI analyses included graph analysis for connectivity and seed-based correlation networks. Independent t-tests were used for comparing the graph parameters and connectivity networks between patients with PD and controls. Results: All subjects were cognitively intact (MMSE > 24). Whole-brain connectivity by graph analysis revealed significant differences between the two groups with decreased global efficiency (Eglob, p < 0.05), increased betweenness centrality (BC) (p < 0.01), and increased characteristic path length (L, p < 0.01) in patients with PD. The functional connections of the default-mode network (DMN), sensorimotor network (SMN), salience network (SN), and hippocampal network (HN) were impaired in patients with PD. Meanwhile, in DMN and SN, elevated connectivity was observed in certain brain regions of patients with PD. Conclusion: Patients with ESRD receiving PD had specific disruptions in functional connectivity. In graph analysis, Eglob, BC, and L showed significant connectivity changes compared to the controls. DMN and SN had the most prominent alterations among the observed networks, with both decreased and increased connectivity regions. Our study confirmed that significant changes in cerebral connections existed in cognitively intact patients with PD.

Project description:IntroductionProteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n?=?183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n?=?186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n?=?89, 37% women, mean age 46 years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p?=?0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C?=?0.777 to C?=?0.799 and C?=?0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p?=?0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

Dataset Information

Association of cardiovascular structure and function with cerebrovascular changes and cognitive function in older patients with end-stage renal disease.

Publications

Association of cardiovascular structure and function with cerebrovascular changes and cognitive function in older patients with end-stage renal disease.

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