The Correlation Between Neuropsychological Changes And Prefrontal Glutamate And ?-Aminobutyric Acid Concentrations Determined By Magnetic Resonance Spectroscopy In Patients With Chronic Kidney Disease Undergoing Maintenance Hemodialysis

Background:The patients with maintenance hemodialysis may occur a variety of neuropsychological changes,such as cognitive impairment,depression,anxiety,etc.These neuropsychological changes may affect the prognosis of maintenance hemodialysis,and increase the mortality and morbidity risk of patients.There are some studies have shown that prefrontal glutamate(Glu)and gamma-aminobutyric acid(GABA)levels are related to a series of neuropsychological changes included cognition,depression,and anxiety,though,there are few studies on the correlation among neuropsychological changes and these chemical substances in these patients with maintenance hemodialysis.Magnetic resonance spectroscopy(MRS)is a noninvasive method for detecting and quantifying local metabolites and neurotransmitters in vivo,that could possibly provide a measurable biomarker for the diagnosis of neuropsychological diseases.Objective:This study attempts to detect the absolute concentration of Glu and GABA in the prefrontal cortex of maintenance hemodialysis patients by using magnetic resonance spectroscopy,and to explore the correlation among neuropsychological changes and Glu and GABA.This study intends to search for a candidate biomarker to evaluate quantificationally neuropsychological changes of maintenance hemodialysis patients primarily,and then investigate the neurochemical mechanisms underlying neuropsychological changes,and finally provide a basic theory for clinical assessment,severity estimation and directing psychotherapy.Materials and Methods:Twenty-nine maintenance hemodialysis patients(19 male,10 female,mean age 56.13±14.5 years)and twenty-nine healthy controls(12 male,17female,mean age 54.00±17.90)participated in this study.The spectra of Glu and GABA in the prefrontal cortex of subjects were collected on the Siemens MAGNETOM Skyra 3.0T magnetic resonance scanner(Siemens Healthcare Gmbh,Munich,Germany),using the Optimal TE sequence and the MEGA-PRESS sequence.Two phantom which one is 50mM Creatine and another one is 50 mM GABA were measured before each MRS session using an external reference or the absolute quantification analysis.The jMRUI v5.0software package was used to quantify Glu and GABA concentrations.And neuropsychological scales included Montreal Cognitive Assessment(MoCA),self-rating depression scale(SDS)and self-rating anxiety scale(SAS)were used to evaluate subjects'cognitive function,anxiety and depression.The correlation between neuropsychological changes and the concentration of glutamate and?-aminobutyric acid in the prefrontal cortex of maintenance hemodialysis was analyzed.Two independent samples t test were used to compare the differences in the absolute Glu and GABA concentration in the two groups.Spearman correlation analysis was used to evaluate the correlation between the absolute Glu and GABA concentrations in the prefrontal cortex and neuropsychological change in maintenance hemodialysis patientsResults:(1)There are significant differences among MoCA,SDS and SAS scores between maintenance hemodialysis patients,compared to healthy control group(P<0.05).The study shows negative correlation between the MoCA scores and Glu concentrations in maintenance hemodialysis patients,but a positive correlation with?-aminobutyric concentration(P<0.05).The SDS scores are positively correlated with the Glu concentrations in maintenance hemodialysis patients,and is negatively correlated with the GABA levels(P<0.05).And the SAS scores are not correlated to neither Glu nor GABA concentrations in maintenance hemodialysis patients(P>0.05).(2)Compared to healthy control group,the Glu concentration in the prefrontal cortex of the maintenance hemodialysis patients is higher,while the GABA concentration is lower,and these shows significant difference between the two groups(P<0.001).The Glu and GABA concentrations at 36 months and 60 months are significantly different from those at 12months(P<0.05),indicating that Glu and GABA may reach its peak concentrations after36 months of dialysis and continue to maintain a higher or lower level.(3)The severity of cognitive function and depression in maintenance hemodialysis patients was statistically different from age,Glu concentration and GABA concentration(P<0.05).Conclusions:The patiens with Maintenance hemodialysis have abnormal prefrontal Glu and GABA levels,which are correlated with neuropsychological changes.Therefore,the anomaly of Glu and GABA concentrations in prefrontal cortex could result in neuropsychological changes in patients with maintenance hemodialysis.The detection of prefrontal Glu and GABA concentrations using in vivo ~1H-MRS seems to be expected to be a biomarker for assessing neuropsychological disorders of maintenance hemodialysis patients.