Abstract
ObjectiveThe network connectivity basis of cognitive declines in end-stage renal disease (ESRD) remains unclear. A triple-network model of the salience (SN), executive control, and default mode networks has been suggested to be critical for efficient cognition. Here, we aimed to test the hypothesis that SN may play a role in cognitive impairment in patients with ESRD.Materials and MethodsWe investigated functional connectivity (FC) alterations within the SN between 43 ESRD patients (19 females/24 males, 46 ± 10 years) and 43 healthy controls (HC) (19 females/24 males, 47 ± 10 years), and performed linear support vector machine (LSVM) analysis on significant FC pairs within the SN to discriminate the two groups, and tested the accuracy of the classifier. Association and mediation analyses were conducted among the significant FC pairs within the SN nodes, clinical indicators, and neuropsychological tests scores.ResultsWe identified significant between-group FC pairs within the SN and fairly good classification efficiency with significant accuracy (72.09%, p < 0.001). We found that FC between the right supramarginal gyrus and right anterior insula (AISL) was positively correlated with MoCA (r = 0.4010, p = 0.008); FC between the dorsal anterior cingulate cortex (dACC) and left AISL was positively correlated with the level of hemoglobin (r = 0.4979, p < 0.001). Mediation analysis found that the indirect effect of hemoglobin on forward digit span test scores via the FC between the dACC and right AISL (p < 0.05).ConclusionDisrupted SN connectivity may help explain cognitive declines in ESRD patients and act as a potential early biomarker. Moreover, the SN connectivity may interact with anemia to promote cognitive impairment.
Highlights
End-stage renal disease (ESRD) is a final condition of kidney function decline with a glomerular filtration rate (GFR) of less than 15 mL/min/1.73 m2 (Webster et al, 2017)
We hypothesized that salience network (SN) connectivity is altered in ESRD and can be discriminated from healthy controls (HC), and we further investigated the relationship between the altered functional connectivity (FC) within the SN, cognitive function, and ESRD
We obtained frame-wise displacement (FD) parameters from the head motion parameters, performed two-sample independent t-tests on the mean FD power to test if there were statistical differences between the ESRD and HC group, we reported the mean value of each group and the statistical values
Summary
End-stage renal disease (ESRD) is a final condition of kidney function decline with a glomerular filtration rate (GFR) of less than 15 mL/min/1.73 m2 (Webster et al, 2017). ESRD is associated with significant brain injury, for example high levels of uremic toxins (UT) in the blood and brain (De Deyn et al, 2009; Watanabe et al, 2014), prevalent anemia (Kurella Tamura et al, 2011), high incidence of vascular risk factors, and chronic inflammation, which may together promote cerebral small vascular injury, endothelial dysfunction, neurodegenerative alterations, and disturbances of the autonomic nervous system (Kooman et al, 2014; Toyoda, 2015) It is unclear how these risk factors induced by renal dysfunction influence brain function, especially cognition
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