| End-stage renal disease(ESRD)is the five stage of chronic kidney disease(CKD),in which the glomerular filtration rate is less than 15ml/min/1.73m2 and the renal function is comprehensively and irreversibly damaged.According to the epidemiological investigation report of nephropathy in China,the prevalence of CKD is as high as 10.8%,and the prevalence of ESRD is as high as 1%.CKD has become an important public health problem in China.Many studies have shown that 40%-70% of ESRD patients have the accompanying symptoms of cognitive impairment,however,the clinical symptoms of cognitive impairment are often overlooked.Cognitive impairment not only affects the quality of life of ESRD patients and imposes additional psychological and economic burdens on them,but also significantly correlated with the mortality rate.However,the potential relationship between ESRD and cognitive impairment is still unclear.According to kidney-brain crosstalk theory,the brain and kidney share the same anatomic and vasoregulatory systems,they are easily affected by common risk factors.Therefore,except the kidney damage,ESRD patients also suffer brain structure change.As one of the main structures of the central nervous system,white matter plays an important role in maintaining normal brain communication and coordinating the normal operation of brain.When white matter microstructure changed,the brain function will be affected.Therefore,exploring the changes of the white matter microstructure of ESRD patients can help us understand the damage pattern of the brain structure in ESRD patients.In addition,it can also help us understand the potential mechanism of the brain structure change and functional abnormality in ESRD patients.In order to study the changes of the white matter microstructure of ESRD patients,this paper mainly analyzed the white matter microstructure of ESRD patients from three levels: whole brain,local region and subnetwork.The fiber bundle analysis methods are as follows:tract-based spatial statistics(TBSS),fixel-based analysis(FBA)and tractography atlas-based analysis(TABS).The main results are as follows:First,the microstructure characteristics of whole brain white matter in patients with ESRD.To explore the microstructure changes of whole brain white matter in ESRD patients,64 ESRD patients and 64 age-matched healthy controls were recruited and all subjects were scanned for diffusion tensor imaging(DTI).Subsequently,TBSS and FBA methods were used to analyze the DTI data of ESRD patients and healthy controls to explore the changes of white matter microstructure and morphology.The results of the TBSS method showed that the patients with ESRD showed altered white matter microstructure mainly in the cingulate bundles.The results of the FBA method showed similar results,that is,the loss of fiber density was found on the cingulate bundles.This study only revealed the damage of brain structure of ESRD patients from the perspective of whole brain,and provided strong imaging evidence for the influence of kidney disease on brain structure.Secondly,local white matter microstructure characteristics in patients with ESRD.Based on the results of previous chapter,we found that the white matter microstructure of ESRD patients mainly located in the cingulate bundles,which is a key region for cognitive control.The potential relationship between the microstructure change of the cingulate bundles in ESRD patients and the cognitive control ability of ESRD patients is still unclear.In order to explore the relationship between ESRD,cingulate bundles and cognitive control ability,64 ESRD patients and 64 healthy subjects with matching age,gender and education degree were recruited in this study.All subjects were scanned with DTI data.The TABS method was applied to detect the group-difference along the fiber bundles,with the cingulate bundles as the region of interest.The TABS results show that the white matter microstructure of ESRD patients along the cingulate bundles was changed.In order to explore the cognitive control ability of the subjects,all subjects performed the color-word Stroop conflict experiment.The results showed that the cognitive control ability of ESRD patients was decreased.Finally,the results of mediation analysis showed that the changes of the white matter microstructure in ESRD patients were the mediating factors of low hemoglobin level affecting the cognitive control ability.In this study,the potential relationship between ESRD,brain and behavior was explored from the perspective of the region of interest.Finally,the characteristics of white matter microstructure of working memory network in patients with ESRD.The brain is the most complex organ in human.The cognitive processing of human is mainly carried out by the coordination of various brain regions.Therefore,all related brain regions should be analyzed in the form of network when exploring a cognitive behavior.In additon,all ESRD patients need dialysis to maintain life,however dialysis had unkown effects on the brain structure of ESRD patients.To explore the effect of ESRD on the brain structure of patients,56 ESRD patients without dialysis and 56 healthy subjects with matching age,gender and education degree were recruited in this study.Working memory was used as the research carrier to explore the white matter microstructure characteristics related to the working memory network of ESRD patients without dialysis.First,all subjects were tested by n-back experiment to test the working memory ability in ESRD patients.The results showed that the working memory capacity of ESRD patients were reduced.All brain regions associated with working memory were subsequently obtained using a meta-analysis,mainly located in the frontal lobe,temporal lobe and parietal lobe.Five fiber bundles connected by bilateral prefrontal lobe-temporal lobe,bilateral prefrontal lobe-parietal lobe,and prefrontal lobe of left brain-prefrontal lobe of right brain were obtained by using the prefrontal lobe as the region of interst.TABS method was used to ditect the group-difference of the five fiber bundles.The results of TABS showed that the white matter microstructure of five working memory related fiber bundles had changed,indicating that the information transfer between the working memory brain regions was affected.Stepwise regression analysis and Pearson correlation analysis were performed on working memory related white matter fiber bundles,blood biochemical indexes and the results of measurement of n-back.The results showed that uric acid was a clinical risk factor for the decline of working memory in ESRD patients.Our results suggest that the decline of working memory in ESRD patients may be related to the microstructure changes of white matter of the working memory regions.This study mainly explores the changes of white matter microstructure in ESRD patients without dialysis experience from the perspective of subnetwork.The results of this study fully illustrate the effect of ESRD itself on brain structure.In summary,this paper mainly investigated the microstructure characteristics of white matter in ESRD patients from multiple levels and perspectives.The study found that ESRD affects the white matter microstructure of the brain and related cognitive function.This study can help us to understand the pathophysiological mechanism of kidney disease to brain structure,also suggest the importance of neuroprotection during the treatment of ESRD patients. |
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