MRI Study Of The Brain Asymmetry And Brain Network In Patients With Vascular Cognitive Impairment

PART ? MRI STUDY OF GRAY MATTER ASYMMETRY IN PATIENTS WITH VASCULAR COGNITIVE IMPAIRMENTObjective Current studies on the correlation between asymmetry and cognitive impairment have focused on Alzheimer's disease(AD)and AD-related mild cognitive impairment(MCI).Vascular cognitive impairment(VCI)is a heterogeneous group of disorders caused by multiple vascular factors,including mild vascular cognitive impairment(m VCI)and vascular dementia(Va D).Mild vascular cognitive impairment is considered to be the prodromal stage of Va D,and Va D is the second most common type of dementia after Alzheimer's disease(AD).The purpose of this study was to investigate changes in gray matter asymmetry and their relationship with cognitive impairment in patients with VCI using voxel-based morphological measurements.Methods Fifty-nine subcortical ischemic vascular disease(SIVD)patients with(subcortical vascular cognitive impairment,SVCI,N = 30)and without(pre-SVCI,N = 29)cognitive impairment and 30 normal controls(NC,N = 30)underwent neuropsychological examinations and multimodal magnetic resonance imaging(MRI)scanning including high-resolution structural MRI and fluid attenuated inversion recovery sequence.All subjects were right-handed.First,white matter hyperintensity(WMH)was segmented and filled by lesion growth algorithm,and WMH volume was calculated.Then,VBM method was used to calculate the gray matter volume asymmetry index(AI)in bilateral hemisphere.The differences in demographic characteristics and gray matter asymmetry among the three groups were estimated using one-way ANOVA.Findings resulting from the group comparisons were corrected for multiple comparisons using nonparametric threshold-free cluster enhancement(TFCE)with 5,000 permutations and while controlling the family-wise error(FWE)rate at p < 0.05.Moreover,partial correlation analysis was performed to explore the relationships between the asymmetry index(AI)values and cognitive assessments controlled for age,sex,and education.Results Significant differences among the three groups regarding the gray matter asymmetry in the fusiform and parahippocampal gyruses were found by ANOVA(F=15.978,P < 0.05).The gray matter asymmetries in the fusiform and parahippocampal gyruses of the SVCI group were significantly different from those of the NC group(t=4.408,P < 0.05)and the pre-SVCI group(t=5.197,P < 0.05),while no differences were found between the NC group and the pre-SVCI group.More specifically,in the fusiform and parahippocampal gyruses,the SVCI group displayed a dramatic rightward asymmetry,whereas the NC group and pre-SVCI group exhibited a marked leftward asymmetry.The results of the correlation analysis showed that the AI values were positively correlated with MMSE(r=-0.515,P<0.001),AVLT immediate recall(r=-0.485,P <0.001),AVLT delayed recall(r=-0.425,P <0.001),AVLT recognition recall(r=-0.513,P <0.001),BNT(r=-0.406,P <0.001),CFT delayed recall(r=-0.338,P =0.002),Stroop1 test(r=-0.410,P <0.001)and Stroop2 test(r=-0.476,P <0.001),and significantly negatively correlated with TMT-A(r=0.447,P <0.001)and TMT-B(r=0.450,P <0.001)test.Conclusion This study demonstrated different lateralization in the fusiform and parahippocampal gyruses of SIVD patients with cognitive impairment compared to healthy subjects and SIVD patients without cognitive decline.Our findings may contribute to better understanding the possible mechanism of cognitive impairment in patients with SIVD,and they suggest the possibility of using gray matter asymmetry as a biomarker for disease progression.PART ? VOXEL-MIRRORED HOMOTOPIC CONNECTIVITY IN PATIENTS WITH VASCULAR COGNITIVE IMPAIRMENTObjective To explore the relationship between the homotopic connectivity and cognitive impairment in patients with vascular cognitive impairment by voxel-mirrored homotopic connectivity(VMHC)analysis.Methods The subjects were as same as in Part I.All subjects underwent cognitive neuropsychological assessment and multimodal MRI scanning including high-resolution T1-weighted imaging and blood oxygen level dependent(BOLD)resting-state functional magnetic resonance imaging.The homotopic functional connectivity between hemispheric symmetric voxels in all subjects were calculated by VMHC method.One-way ANOVA was used to compare the differences in demographic characteristics,neuropsychological assessment results and VMHC among the normal control group(NC),SIVD patients without cognitive impairment(pre-SVCI)and SIVD patients with cognitive impairment(SVCI).The post hoc test was conducted.The Family wise error(FWE)method based on voxel was used for multiple comparisons(P < 0.05).Finally,the partial correlation analysis was conducted by using age,gender,years of education and frame-wise displacement(FD)as covariates to explore the relationship between VMHC values of the significantly different regions and cognitive assessment results.Results One subject with excessive head movement during BOLD scanning was excluded.A total of 88 subjects were included in this part.The VMHC of insula was significantly different among the three groups(F=20.118,P < 0.05).VMHC of insula in the pre-SVCI group(t=4.565,P <0.05)and the SVCI group(t=6.305,P < 0.05)was lower than that in the NC group,while there was no significant difference in VMHC of insula was found between the pre-SVCI group and the SVCI group.Partial correlation analysis showed that VMHC values of insula were positively correlated with MMSE(r=0.361,P<0.001),AVLT immediate recall(r=0.515,P<0.001),AVLT delayed recall(r=0.620,P<0.001),AVLT recognition recall(r=0.604,P<0.001)and Stroop2 test(r=0.464,P<0.001),and significantly negatively correlated with TMT-A(r=-0.442,P<0.001)and TMT-B(r=-0.510,P<0.001)test.Conclusion Compared with normal controls,VMHC in insula of SIVD patients was significantly decreased,and the value of VMHC in insula was significantly related to cognitive function.The results of this study suggest that dysregulation of intrinsic functional connectivity between symmetric voxels of different hemispheres may be a potential mechanism of SIVD.PART ? MRI STUDY OF BRAIN FUNCTIONAL NETWORK IN PATIENTS WITH VASCULAR COGNITIVE IMPAIRMENTObjective To explore the changes of functional connectivity in voxel level and network topologic properties of brain functional network in patients with vascular cognitive impairment by using voxel-based degree centrality(DC)analysis and graph theory based brain network analysis,revealing the possible mechanism of cognitive impairment in patients with vascular cognitive impairment caused by changes in brain functional networks.Methods The subjects were the same as in Part I and all patients with subcortical ischemic vascular disease were followed up(mean follow-up time: 498.32 ± 20.03 days).All subjects underwent cognitive neuropsychological assessment and multimodal MRI scanning including high-resolution T1 weighted imaging and resting-state functional magnetic resonance imaging based on blood oxygen level dependent(BOLD).After that,the steps of data analysis were as follows:(1)using voxel-based degree center analysis method to process BOLD imaging data,calculate the degree centrality of all voxels.One-way ANOVA was used to compare the differences of the demographic characteristics,neuropsychological assessment and DC among three groups of normal control(NC),SIVD without cognitive impairment(pre-SVCI)and SIVD with cognitive impairment(SVCI);Partial correlation analysis was used to analyze the relationship between DC values of the regions with significant differences and results of cognitive assessment.(2)Global and local topological properties of brain functional network of all subjects were calculated using graph theory-based network analysis.Then the demographic characteristics,neuropsychological assessment results and topological properties of brain functional network among NC group,pre-SVCI group and SVCI group were compared using one-way ANOVA,and partial correlation analysis was used to explore the correlation between the significantly different network properties and cognitive assessment results;Repeated measures ANOVA was performed to analyze the difference of topological properties of brain functional network in pre-SVCI group and SVCI group at baseline level and follow-up level.Results(1)The results of DC analysis showed that there were significant differences in DC in the left insula and bilateral sensorimotor areas among three groups(left insula:F=18.643,P < 0.05;left sensorimotor area:F=16.742,P < 0.05;right sensorimotor area:F=14.291,P < 0.05).Compared with NC group,DC of left insula was significantly decreased in pre-SVCI group(t=4.252,P < 0.05),and DC of left insula and bilateral sensorimotor areas were significantly decreased in SVCI group(left insula:t=5.837,P <0.05;left sensorimotor area:t=5.749,P < 0.05;right sensorimotor area:t=5.142,P < 0.05).In addition,DC of left sensorimotor area in SVCI group was significantly lower than that of pre-SVCI group(t=4.296,P < 0.05).The DC values in left insula and bilateral sensorimotor areas were significantly correlated with the results of cognitive assessment results involving memory and executive function.(2)We also found that there were significant differences in the clustering coefficient and degree centrality of right precentral gyrus and left supramarginal gyrus among NC group,pre-SVCI group and SVCI group by graph theory based brain network analysis(clustering coefficient : F=3.399,P < 0.05;DC of right precentral gyrus:F=9.830,P < 0.0;DC of left supramarginal gyrus:F=11.654,P < 0.05).The clustering coefficient and degree centrality of right precentral gyrus and left supramarginal gyrus in SVCI group were lower than those in NC group(clustering coefficient:t=3.470,P < 0.05;DC of right precentral gyrus:t=4.712,P < 0.05;DC of left supramarginal gyrus:t=5.304,P < 0.05).Clustering coefficient and degree centrality of right precentral gyrus and left supramarginal gyrus were also closely related to memory function and executive function.Repeated measures ANOVA did not find significant inter-group differences between pre-SVCI group and SVCI group.Conclusion SVCI patients had lower global clustering coefficient and lower degree centrality in sensorimotor region in brain functional network,which indicated the diminished ability of information transmission and the impairment of ability to integrate information.The changes in the topological properties of brain functional networks may be the neural mechanism of cognitive impairment in patients with SIVD.