The Brain Network Characteristics Of Early Onset Versus Late Onset Depression And The Relative Mechanism Of Cognitive Impairment:A Study Of Multimodal MRI

BackgroudAccording to the age of onset,Late life depression(LLD)can be divided into early onset depression(EOD)and late-onset depression(LOD).Because EOD and LOD may share the similar clinical symptoms,but with different pathogenesis.According to our current knowledge,EOD might cause by family history of mental disease and stress event,while,LOD might associated with somatic disease and neurodegenerative disease.Thus,understanding their structure and function characteristics can help us understand the pathogenesis of their diseases and the mechanism of cognitive defict,which would provied some help to prevent AD in an early stage.ObjectiveTo explore the functional and structural characteristics of EOD and LOD and their mechanism of cognitive impairment.MethodThe study included 50 patients with LLD(EOD 15,LOD 35)and 50 health controls(HC).This is the first time to use the multi modality magnetic resonance brain network analysis in investgated the rich-club coefficent,modularity and the network properties of default mode network(DMN)in EOD and LOD.This study is divided into three parts to research.Part one:First,we constructed the white matter network based on AAL90 atlas and performed rich-club analysis in EOD and LOD.Then we compared the difference of rich-club organization between EOD,LOD and HC by AHCOVA.Part two:According to result of rich-club analysis,we considered modularity might have change in LLD,So,we constructed a functional network based on Granger causality analysis,and carrying out a modular analysis in participants.Then we using AHCOVA to compare the similarities and differences between the three groups of subjects.Part three:At last,base on the result of modularity,we conducted that the cognitive deficits in LOD might cause by DMN impair.So,we constructed the function of network,covariance structure network and white matter network in DMN(associated with cognitive function closely).Then we calculated the network properties of DMN through the network graph theory and used the AHCOVA analysis to investgate the different network characteristics among three groups.The relationship between DMN network properties and cognitive function,hippocampal subfields was calculated by Pearson correlation coefficient and linear regression.ResultPart one:Both EOD and LOD patients showed damage in rich-club organization in white matter network compared with HC(P= 0.000207).The global network properties of the white matter network in LOD patients are related to the information processing speed(all P<0.05).Rich-club can also play an important role in integrated information between modulars,the disruption of rich-club might casue the change in modularity.Part two:The Granger function network suggested that function modularity was damaged in EOD(P=0.013)among three groups,and the abnormal activation of the DMN network was appeared in the LLD group(P=0.033).The greater the activation degree of DMN in the functional network of LOD patients,the slower the information processing speed(beta=-0.078;P = 0.042).Indicated that the impaired of DMN might cause cognitive deficits in LOD.Part three:In the network of DMN,compared with HC,the function connectivity of LOD was enhanced(P=0.003),and the covariance structure network suggest that local impaired in LOD was more obviously(P=0.067).Through linear regression,we found that in DMN white matter netwrok the connection strength of right temporal lobe is the influence factors of information processing speed in LOD(beta=15.715;P ?0.012).At the same time,the Eloc in the DMN white matter network is the influence factor of memory function and the speed of information processing in the EOD group(beta=172.441;P = 0.014 and beta=87.417;P = 0.047).Finally,we found that the left hippocampal fissure and the right CA2-3 was related to the connection efficiency of the DMN white matter network and the TI Granger functional network(beta=17.883;P=0.012 and beta=0.427;P=0.041).Conclusion:This is the first study to discover that EOD and LOD were damaged on rich-club network organization in white matter network,and in the functional modularity impairement was mainly affected in EOD.DMN high activation is negative correlated with information processing speed in LOD;and a further study in DMN found that the cognitive impairment of LOD is caused by the local white matter damage in right temporal lobe of DMN.