The Research Of Resting-state FMRI Brain Network Topological Properties And Cognitive Function In Type 2 Diabetes Mellitus

Objective:Resting-state functional magnetic resonance imaging?rs-FMRI?technique was used to construct a binarization whole-brain functional network based on graph theory complex network analysis to investigate the changes of topological properties in type 2 diabetes mellitus?T2DM?patients.In addition,we also explored the potential correlation between the changes of topological properties with fasting blood glucose?FBG?,Hemoglobin Ale?HbAlc?and cognitive function in patients and evaluated the application value of rs-fMRI technique in T2DM patients and the possible mechanism of change in cognitive function,aiming to provide objective imaging basis for clinical diagnosis and therapy.Materials and Methods:From April 2017 to November 2017,a total of 30 T2DM patients?18:12 males to females,age:51.77 ± 1.42 years?and 30 sex-,age-,and education-matched healthy control subjects?18:12 males to females,age:48.87 ± 0.98 years?were recruited from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine.All participants have completed the Montreal Cognitive Assessment Scale-B?MoCA-B?,Auditory verbal learning test?AVLT?,Trail making test-A?TMT-A?,Trail making test-B?TMT-B?,Digit span test?DST?,Grooved Pegboard test and Clock drawing test?CDT?,then completed conventional MRI,rs-fMRI and high-resolution 3D-T1WI whole-brain imaging scan.The data of rs-fMRI were preprocessed by using the brain functional magnetic resonance analysis software to construct the whole-brain binarization functional network,and the topological attribute metrics were calculated based on graph theory complex network analysis,including?1?global topological metrics:clustering coefficient Cp,normalized clustering coefficient y,characteristic shortest path length Lp,normalized characteristic shortest path length ?,small-worldness ?,global efficiency Eglob and local efficiency Eloc;?2?nodal topological metrics:nodal degree,nodal efficiency and nodal betweenness.We selected a appropriate statistical analysis methods to compare the differences between the demographics,biochemical test results,cognitive function of T2DM group and HC group,and compared the differences between the global and local topological attribute metrics with gender,age,education years and BMI as covariates,and to further make correlation analysis,p<0.05 considered statistically significant.Results1.There was no significant difference in gender,age,education years,BMI,short-term delayed memory of AVLT,long-term delayed memory of AVLT,recognition of AVLT,TMT-B,DST and CDT in T2DM group and HC group?p>0.05?.Systolic blood pressure?p = 0.013?and diastolic blood pressure?p = 0.035?in T2DM group were higher than HC group.The scores of MoCA-B?p = 0.010?and AVLT immediate memory?p = 0.016?in T2DM group were lower than those in HC group.The spending time of TMT-A?p=0.018?,Grooved pegboard-R?p = 0.009?and Grooved pegboard-L?p = 0.025?were longer in T2DM group in comparison of HC group.The diabetic duration of T2DM patients was?5.04±4.46?years,FBG was?8.62±3.44?mmol/L and HbAlc was?8.54±2.09?%.2.Comparison of rs-fMRI brain functional network topological metrics2.1 Comparison of global topological metrics between T2DM group and HC group:Compared with random networks,functional brain networks of T2DM group and HC group had relatively higher clustering coefficient?y>1?and similar shortest path length??=1?and the small-worldness ?>1,that is,demonstrated small-world property.We observed differences between T2DM patients and control subjects in some critical small-world properties and network efficiency parameters upon application of pre-defined threshold ranges.T2DM patients showed increased normalized clustering coefficient ??p = 0.019?,??p=0.032?and local efficiency?p =0.034?in cormparison to control subjects.However,?,Cp,Lp and Eglob values were similar between T2DM patients and controls?P>0.05?.2.2 Comparison of local topological metrics between T2DM group and HC group:We identified 27 brain regions with altered nodal metrics between T2DM and control subjects in at least one of the three nodal characteristics.T2DM.patients showed decreased nodal characteristics in right precentral gyrus,right supplementary motor area,right superior frontal gyrus?medial orbital?,right cuneus,left superior frontal gyrus?dorsolateral?,left superior frontal gyrus?medial?,left amygdala,left median cingulate and paracingulate gyri,left supramarginal gyrus,bilateral lingual gyrus,bilateral superior occipital gyrus and middle occipital gyrus compared to controls.However,T2DM patients showed increased nodal characteristics in right gyrus rectus,right anterior cingulate and paracingulate gyri,right posterior cingulate gyrus,left angular gyrus,bilateral caudate nucleus,bilateral cerebelum₃,bilateral cerebelum_crusl,vermis₁₂ and vermis 3 compared to controls.3.Correlation analysis between network topological properties and cognitive functionIn T2DM patients,MoCA-B scores were positively correlated with the nodal degree?r=0.400,p=0.043?and nodal efficiency?r=0.452,p=0.021?of the right gyrus rectus,the immediate memory of AVLT scores was positively correlated with the nodal betweeness of the left amygdala?r = 0.457,p = 0.019?,short-term delayed memory of AVLT scores was positively correlated with the nodal degree of the right cerebelum₃?r = 0.431,p = 0.028?,the spending time of both the Grooved pegboard-R?r =-0.461,p = 0.018?and the Grooved pegboard-L?r =-0.436,p =0.026?were negatively correlated with the nodal betweeness of the right middle occipital gyrus.4.Correlation analysis among FBG,HbAlc and net.work topological propertiesIn T2DM patients,FBG was positively correlated with the nodal degree of the left middle occipital gyrus?r = 0.422,p = 0.023?,HbAlc was positively correlated with the nodal degree of the left superior occipital gyrus?r = 0.372,p = 0.043?and the left middle occipital gyrus?r = 0.382,p = 0.037?and negatively correlated with the nodal betweeness of the right posterior cingulate gyrus?r =-0.388,p=0.034?.5.Correlation analysis among FBG,HbAlc and cognitive functionIn T2DM patients,HbAlc was negatively correlated with the immediate memory of AVLT socres?r =-0.458,p=0.019?and there was no significant correlation between FBG and cognitive function?p>0.05?.Conclusion1.Our study showed that the rs-fMRI brain networks of T2DM patients had altered topological properties compared to controls,even though the conventional MRI demostrated normal,suggesting that T2DM is a crucial factor leading to brain function damage.Furthermore,rs-fMRI technique combined with graph theory-based complex network analysis is a powerful tool to study the changes of T2DM-related brain function and can provide imaging basis for clinical diagnosis and treatment;2.T2DM patients were found to have decreased nodal properties in some important brain regions of occipital visua area,prefrontal gyrus,left median cingulate and paracingulate gyri,while the nodal properties of the right cingulate gyrus,bilateral caudate nucleus,bilateral cerebelum and the global topological properties of?,?,local efficiency were increased,thus indicating that the function of visual network,high-order cognitive control network,DMN and cerebelum had altered and an underlying compensatory mechanism may insist to alleviate the decline of cognitive function;3.T2DM patients had lower scores of some cognitive function scales than HCs,such as memory,attention.and executive function,and the scores were correlated with the local topological attributes of some brain regions,partly explaining the mechanisms of cognitive dysfunction in T2DM patients;4.Partial correlation analysis showed that the value of HbAlc was associated with local topological attributes of some brain regions and the immediate memory of AVLT scores,,suggesting that HbAlc had a significant impact on topological properties and cognitive function.Besides,controlling and monitoring HbAlc is of great significance in the evaluation of clinical diagnosis,treatment and prognosis;5.Diabetes pathogenesis mechanism is complex and still unclear,and there are variety of mixed factors.The rs-fMRI technique combined graph theory-based complex network analysis provides a new insight for the study of T2DM,but there are few related researches,so long-term,large sample,better control groups and follow-up investigations are needed to explore the topological attributes changes of brain network and the pathogenesis mechanisms in future studies.