Preferentially Disrupted Core Hubs Within the Default-Mode Network in Patients With End-Stage Renal Disease: A Resting-State Functional Magnetic Resonance Imaging Study.

Chi Ma,Jian-Cong Fan,Yan-De Ren,Min-Ge Ma,Hua-Wei Su,Fen Tian,Zhan-Hui Li

doi:10.3389/fneur.2020.01032

Abstract

Neuroimaging evidence implies that cognitive impairment in patients with end-stage renal disease (ESRD) is related to the disruption of the default-mode network (DMN). The DMN can be divided into three functionally independent subsystems, which include the cortical hub subsystem [consisting of the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC)], the dorsal medial prefrontal cortex (dMPFC) subsystem, and the medial temporal lobe (MTL) subsystem. However, it is unknown how the functional connectivity (FC) in DMN subsystems is differentially impaired in ESRD. This prospective study was carried out at the Affiliated Hospital of Qingdao University, China, between August 2018 and July 2020. Thirty-two ESRD patients and forty-five healthy controls (HCs) were recruited for this study and received resting-state functional magnetic resonance imaging (rs-fMRI) scanning, and FCs on predefined regions of interest (ROIs) were individually calculated in three DMN subsystems using both ROI- and seed-based FC analyses to examine FC alterations within and between DMN subsystems. The two-sample t-test was used for the comparisons between groups. We also tested the associations between FC changes and clinical information using Pearson's correlation analysis. The results demonstrated that ESRD patients, compared with HCs, exhibit reduced FC specifically within the cortical hubs and between the DMN hubs and two subsystems (the dMPFC and MTL subsystems). Moreover, the FC values between the aMPFC and PCC were positively correlated with creatinine and urea levels in the ESRD patients. Our results suggest that the cortical hubs (PCC and aMPFC) are preferentially disrupted and that other subsystems may be progressively damaged to a certain degree as the disease develops.

Highlights

Individuals with end-stage renal disease (ESRD), defined as a glomerular filtration rate (GFR) of 90% of normal renal function as the end stage of chronic kidney disease (CKD) [1], have a substantially higher prevalence of cognitive impairment than the general population; cognitive impairment is present in a striking 10 to 40% of ESRD patients, depending on the evaluation methods of cognitive impairment and the stage of chronic kidney disease [2]
In the medial temporal lobe (MTL) subsystem, significantly reduced connectivity was found in the posterior inferior parietal lobule (pIPL)-retrosplenial cortex (Rsp) and pIPL-parahippocampal cortex (PHC) regions of interest (ROIs) pair
Seed-based functional connectivity (FC) analysis shows significantly decreased FCs between the posterior cingulate cortex (PCC) and precuneus cortex (Pcu), the PCC and anterior medial prefrontal cortex (aMPFC), and the aMPFC and dorsal medial prefrontal cortex (dMPFC) in patients with ESRD compared with healthy controls (HCs), which were consistent with the results of ROI-based analysis

Summary

Introduction

Individuals with end-stage renal disease (ESRD), defined as a glomerular filtration rate (GFR) of 90% of normal renal function as the end stage of chronic kidney disease (CKD) [1], have a substantially higher prevalence of cognitive impairment than the general population; cognitive impairment is present in a striking 10 to 40% of ESRD patients, depending on the evaluation methods of cognitive impairment and the stage of chronic kidney disease [2]. Cognitive impairment may affect independence, daily functioning, and medication adherence of the patients [3] and is an independent predictor of mortality [4]. Smallvessel cerebrovascular disease, uremic metabolite accumulation, and anemia may be important factors in the development of CKD-related cognitive impairment [6]. Long-term hemodialysis may result in significantly reduced quality of life, contributing to the development of anxiety and depression. It should be noted that even younger ESRD patients have poorer cognitive function than their peers [7]. It would be worthwhile to use a neuroimaging technique to precisely determine how cognitive impairment affects the brain, as it may provide a sensitive neurobiological signature that would enable earlier, accurate clinical diagnosis and allow an effective therapeutic intervention What are the neuropathological mechanisms of cognitive dysfunction in ESRD patients? It would be worthwhile to use a neuroimaging technique to precisely determine how cognitive impairment affects the brain, as it may provide a sensitive neurobiological signature that would enable earlier, accurate clinical diagnosis and allow an effective therapeutic intervention

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