Changes Of Hippocampal Structure And Function And Memory Impairment In Subcortical Ischemic Cerebrovascular Disease:a MRI Study

PART 1 Relationship between Structural Changes in Hippocampal Subregions and Memory Impairment in Subcortical Ischemic Cerebrovascular DiseaseBackground and Purpose:Subcortical ischemic vascular disease(SIVD)patients are suffered memory disorder thought to be related with hippocampus.We aimed to explore alterations of hippocampal subregions,and the relationship between different hippocampal subfield volumes and different memory dysfunctions in SIVD patients.Methods:Total 77 SIVD patients with cognitive impairment(SIVD-CI,n=39)and normal cognition(SIVD-NC,n=38)and 41 matched healthy controls(HC group)were included in the study.All subjects were measured memory function and scanned structural MRI.Then,hippocampus was segmented and measured by FreeSurfer 6.0 software.One way ANOVA was used to compare clinical and neuropsychological data among the three groups.Analysis of covariance was used to compare the hippocampal subregion volumes of the three groups,age,gender,education and ICV used as covariates.Then post hoc t-test was used to evaluate differences between each group-pair,multiple comparison was corrected by false discovery rate(FDR),p<0.05.Finally,we tested the correlation between statistical different volumes of hippocampal subfields and memory scores,age,gender,education and ICV were controlled.Results:Almost all the volume of hippocampal subareas were statistically different among the three groups except for bilateral hippocampal fissure(p-0.366,p-0.086)and left parasubiculum(p=0.166).After multiple correction for FDR,the volumes of bilateral hippocampal tail,subiculum,CA1,presubiculum,molecular layer HP,GC-ML-DG,CA3,CA4 and fimbria were significantly smaller in SIVD-CI and SIVD-HC group than those in HC group(p<0.05).Furthermore,SVCI-CI patients showed smaller volume in right subiculum(p<0.001),CA1(p=0.002),presubiculum(p=0.002),Molecular layer HP(p=0.017)compared to SIVD-NC group.In addition,right subiculum volume was positively related to Rey’s Auditory Verbal Learning Test(RAVLT)word recognition(r=0.230,p=0.050),Backward Digit Span Task(R-DST)(r=0.326,p=0.005)and Rey-Osterrieth complex figure test(ROCF)immediate recall score(r=0.247,p=0.035),right CA1 volume was positively correlated to RAVLT word recognition(r=0.261,p=0.026),right presubiculum volume showed positive relationship with R-DST(r=0.254,p=0.030)and ROCF immediate recall score(r=0.242,p=0.039).Conclusions:SIVD might lead to general reduction volume in multiple hippocampal subareas.However,SIVD-CI patients showed specific atrophy subfields in right subiculum,CA1,presubiculum,and Molecular layer HP,which might be associated with memory deficits in SIVD.PART 2 Relationship between Founctional Changes in Hippocampal Subregions and Memory Impairment in Subcortical Ischemic Cerebrovascular DiseaseObjective:To investigate the changes of functional connectivity(FC)between hippocampal subregions and whole brain in patients with subcortical ischemic vascular disease(SIVD),and the relationship between these changes and memory score.Methods:After excluding subjects with head translation>2mm and/or rotation>2°,32 patients with cognitive impairment(SIVD-CI group),33 patients with normal cognition(SIVD-NC group)and 38 matched healthy controls(HC group)were included in this study.The resting-state functional magnetic resonance imaging(fMRI)data of each subject were collected.Then,using GIFT software(the bilateral hippocampus in the automatic anatomical label(AAL)as templates,and the estimated score was 12)to do the Independent component analysis(ICA)to obtain the functional template of each subregion of the bilateral hippocampus.Then,each subregion was taken as the region of interest(ROI),and the voxel-based FC maps of the three groups were obtained by the DPABI software.One-way ANOVA was used to compare the differences of FC between hippocampus and whole brain among the three groups,with age,gender and education as covariates.After that,post hoc t-test was used to compare the differences between each two groups,and cluster level FWE was used to correct multiple comparisons.The initial threshold was set as p<0.001 and cluster level p<0.05.Finally,age,gender and education were used as covariates to analyze the partial correlation between memory scores and FC values of abnormal brain regions in SIVD subgroup.Results:Except for the left CA1 and t right hippocampal tail,the FC between almost all the hippocampal subareas and frontal lobe,limbic lobe and cingulate gyrus were significantly different among the three groups.In addition to bilateral hippocampal tail and left CA3,FC between hippocampal subregions and temporal lobe also showed differences among the three.Further comparison between the two groups,compared to HC:(1)the FC values of all hippocampal subregions(except right hippocampal tail)and frontal lobe,marginal lobe,cingulate gyrus in SIVD-CI patients were lower;(2)the FC values of left hippocampal fissure,subiculum,right CA3,CA4,fimbria,GC-ML-DG,molecular layer HP,presubiculum,bilateral parasubiculum and frontal lobe in SIVD-NC patients were lower;(3)the right CA1,CA3,CA4,fimbria,HATA,molecular layer HP,bilateral hippocampal fissure,GC-ML-DG,parasubiculum,presubiculum and subiculum in SIVD-CI patients,and the FC between most left hippocampal subregions,right CA3,fimbria,presubiculum and temporal lobe in SIVD-NC group increased;(4)The FC between most left hippocampal subregions and occipital lobe,posterior cerebellar lobe in SIVD-NC patients were increased.In SIVD subgroup,the FC values of left CA1,HATA and cerebellar lobes(posterior and anterior)in SIVD-CI group were lower than those in SIVD-NC group.In SIVD patients,the FC value of left CA1 and posterior anterior cerebellar lobe was positively correlated with the immediate recall(r=0.440,p=0.001),delayed recall(r=0.398,p=0.002)of RAVLT,DST(r=0.372,p=0.004),R-DST(r=0.314,p=0.018);the FC value of left HATA and posterior anterior cerebellar lobe was positively correlated with the immediate recall(r=0.443,p=0.001),delayed recall(r=0.402,p=0.002)of RAVLT,DST(r=0.380,p=0.001),004),R-DST(r=0.339,p=0.010).Conclusion:The differences of FC in hippocampal subregions and whole brain of SIVD patients were mainly manifested in frontal lobe,limbic lobe and cingulate gyrus as well as temporal lobe.And SIVD-CI patients showed a decrease in FC of frontal lobe,marginal lobe and cingulate gyrus and an increase in FC temporal lobe;SIVD-NC showed a decrease in FC of frontal lobe and an increase in FC of temporal lobe.The FC between left CA1,HATA and posterior cerebellar lobe of SIVD-CI patients were significantly lower than that of SIVD-NC group,which may be related to memory dysfunction in SIVD patients.