Structural And Functional Brain Networks In Patients With Diabetic Kidney Disease:A Graph Theory-based Magnetic Resonance Imaging Study

PART I Brain Structural Networks Alterations in Patients with Diabetic Kidney Disease:A Graph Theory-based Magnetic Resonance Imaging StudyPurpose:To explore the white matter brain network changes in patients with diabetic kidney disease(DKD)using graph-based analysis,and further evaluate the relationship between network properties and cognitive function in these patients.Materials and methods:Sixty-two DKD patients(DKD group,age:53 ± 9 years,male/female:42/20),60 diabetes mellitus(DM)patients without renal complications(DM group,age:52±12 years,male/female:40/20)and 80 age,sex and educational level matched healthy volunteers(control group,age:49 ± 13 years,male/female:52/28)were enrolled in this study.All subjects underwent diffusion tensor imaging(DTI),laboratory tests,and neuropsychological assessments.Graph theory was used to analyze the network topological properties of the white matter network of the three groups.DKD patients were divided into two groups according to estimated glomerular filtration rate(estimated glomerular filtration rate of higherthan 60 ml/min/1.73m2 for the CKD1-3 group,glomerular filtration rate lessthan 60 ml/min/1.73m2 for the CKD4-5 group)to further analyze the effect of renal function on the white matter network of the brain.Finally,the correlation between these network indicators and cognitive scores and laboratory test results was calculated.Results:The white matter network of the three groups showed obvious small-world properties.There was no significant difference in the network topology between the DM group and the control group(all P>0.05).Compared with the DM group and the control group,the DKD group showed increased characteristic path length(Lp)(P =0.025 and 0.023,respectively)and decreased global efficiency(Eg)(P<0.001 and P<0.O01,respectively)and local efficiency(Eloc)(P<0.001 and P<0.001,respectively);In the nodal properties,nodes in the parietal lobe,occipital lobe,and basal ganglia showed decreased node efficiency,while nodes in the parietal lobe showed reduced node degree.The DKD group showed decreased structural connectivity in the dorsal attention network compared to the DM group.These changes were correlated with the patient’s cognitive scores and laboratory test results.The above-mentioned changes aggravated with the decreased renal function.Conclusions:The white matter network of DKD patients showed changes in global and nodal topological properties.These changes were correlated with cognitive scores and laboratory test results.Changes in white matter network may be the neurological mechanisms leading to cognitive impairment.Decreased renal function is a major risk factor for white matter network damage.Part II Brain Functional Networks and Structural-Functional Coupling Alterations in Patients with Diabetic Kidney Disease:A Graph Theory-based Magnetic Resonance Imaging StudyPurpose:To explore the brain functional network changes and functional-structural coupling changes in patients with diabetic kidney disease(DKD)using graph-based analysis,and further reveal the neural mechanism of cognitive impairment in patients with DKD.Materials and methods:Sixty twopatients with DKD(DKD group,age:53 ± 9 years,male/female:42/20),60 diabetes mellitus(DM)patients without renal complications(DM group,age:52 ± 12 years,male/female:40/20)and 80 age,sex and educational level matched healthy volunteers(control group,age:49 ± 13 years,male/female:52/28)were enrolled in this study.All subjects underwent resting-state functional MRI(rs-fMRI)scans,laboratory tests,and neuropsychological assessments.Graph theory was used to analyze the network topological properties of the functional network of the three groups.The functional-structural coupling values of the three groups were calculated.DKD patients were divided into two groups according to estimated glomerular filtration rate(estimatedglomerular filtration rate of higherthan 60 ml/min/1.73m2 for the CKD1-3 group,glomerular filtration rate lessthan 60 ml/min/1.73 m2 for the CKD4-5 group)to further analyze the effect of renal function on the functional network of the brain.Finally,the correlation between these network indicators and cognitive scores and laboratory test results was calculated.Results:The functional network of the three groups showed obvious small-world properties.The DKD group showed decreased standardized clustering coefficient(y)and normalized characteristic path length(λ)than the control group(P = 0.010,0.001,respectively).In terms of characteristic path length(Lp),there were significant differences among the three groups.The Lp values of DKD group,DM group,and control group decreased in turn(DKD-DM:P value=0.020,DKD-HC:P<0.001 and the DM-HC:P<0.001).In terms of global efficiency(Eg)and local efficiency(Eloc),there were significant differences among the three groups.The Eg value and Eloc value of DKD group,DM group and control group increased in turn(DKD-DM:P=0.031,0.033,respectively;DKD-HC:P<0.001,<0.001,respectively;DM-HC:P<0.001,0.001,respectively).In terms of node properties,the DKD group had lower node efficiency in the prefrontal,parietal lobe,occipital lobe,and basal ganglia-related brain regions than the control group,and decreased node degrees in the prefrontal,frontal,occipital,and basal ganglia-associated brain regions.DM group had similar performance as control group,but the degree was lower than DKD group,DKD group showed decreased nodal efficiency and nodal degree in some brain regions compared to the DMgroup.Compared with the control group,the patients groups showed a wide range of functional connectivity changes.The DKD group showed decreased functional connectivity in the dorsal attention network and executive control network compared to the DM group.In terms of structure-function coupling,the DM group showed structural-functional decoupling compared to the control group,whereas the DKD group had no significant difference compared to the control group.Conclusion:The DKD patients showed enhanced functional brain network disruption compared with DM patient,and these alterations will be more obviously when the renal function decline.DM group exhibit structural-function network decoupling,but the DKD group showed normal appearing structural-function coupling compared with controls,which may be associated with deceasedbrain structural and functional network changes of DKD patients.