| Objective:The aim of this study is to investigate the characteristics of memory deficits and hippocampal substructures and functions in the elderly with Type 2 Diabetes Mellitus complicated with Mild Cognitive Impairment(T2DM-MCI),hoping to clarify the possible mechanism of memory impairment of T2DM-MCI patients so as to provide theoretical basis for the early diagnosis and treatments.Methods:Using cross-sectional study design,the eligible participants were enrolled from communities of Fuzhou City,according to the inclusion and exclusion criteria.During the process of study,the patients in T2DM-MCI group were firstly enrolled and then we recruited participants of Mild Cognitive Impairment without Type 2 Diabetes Mellitus group(MCI group),Type 2 Diabetes Mellitus without Mild Cognitive Impairment group(T2DM group)and Normal Control group(NC group)through matching their age,gender and years of education.This study had enrolled 135 participants,while there were 10 outliers of hippocampal volume among them which were excluded out of analysis.Finally,125 participants were included into statistical anlysis of this study,including T2DM-MCI group(N=31),MCI group(N=33),T2 DM group(N=30)and NC group(N=31).The eligible participants were evaluated using neuropsychological tests and detected using blood biochemical indicators examination(such as fasting blood glucose,glycosylated hemoglobin and etc.)and brain MRI to obtain T1 structure image and resting-state functional MRI image.We had applied Wechsler Intelligence Scale(WMS),Rey Auditory Verbal Learning Test(RAVLT)and Rey-Osterrith Complex Figure Test(ROCF)to evaluated the general memory,verbal memory and visual memory separately.In the statistical anlysis,among groups,the one-way ANOVA or rank-sum test was applied according to data distribution.In the MRI analysis process,to analyse T1 structural MRI data,Freesurfer 7.1.0 software was used for the preprocessing and segmentation of hippocampal subregion along the longitudinal axis,containing head,body and tail.The general linear model analysis was performed to compared th group differences of hippocampal subregions volume.Then,we had segmented the subregions that with significant group difference into subfields along its transversal axis.After Bonferroni correction,the partial correlation analysi was conducted to probe the relationships between volume of hippocampal subregions and memory functions,controlling for age,gender,years of education,years of diabetes,Geriatric Depression Scale-15(GDS-15),history of hyperlipidemia,high-/low-density lipoprotein and total intracranial volume(TIV).For the analysis of resting-state f MRI,the SPM12 and DPABI 6.0 sofwares were applied for preprocessing.Due to the significant group difference of right hippocampl body that calculated in above analysis,it was set as the region of interst for voxel-wise functional connectivity analysis.Then,the parietal correlation analysis between functional connectivity and memory functions was explored.Results:1.The results of general demographic information showed that there were no significant differences in age,gender,years of education,level of insulin and triglyceride,total cholesterol and TIV among the four groups(P>0.05).Compared with NC group,T2 DM group and MCI group,the level of high-density lipoprotein of T2DM-MCI group were signicantly lower,while the scores of GDS-15 were higher(P<0.001).Compared with NC group,the level of low-density lipoprotein of T2DM-MCI group were lower(P<0.001).2.The results of comparison for the neuropsychological tests among groups showed that compared with MCI group,the scores of RAVLT delayed recall subtest(P=0.025)and ROCT recall subtest(P=0.025)were significantly decreased in T2DM-MCI group.Compared with NC group,T2 DM group showed significantly lower score of ROCF recall subtest(P=0.029).3.Results of general linear model analysis for hippocampal subregion volume showed that compared with NC group,the volumes of right hippocampal body in the T2DM-MCI group were significantly smaller(P=0.004,Bonferroni correction).Compared with T2 DM group,volumes of right hippocampus body in T2DM-MCI group were decreased(P<0.001,Bonferroni correction).But there was no significant difference between T2DM-MCI group and MCI group(P>0.05/3,Bonferroni correction).Besides,the results of comparison of subfields showed that compared with NC group,the volumes of CA1,CA3 and mocular layer body in T2DM-MCI group were significantly decreased(P=0.002,P=0.002,P=0.002,Bonfferroni correction).Compared with T2 DM group,the volumes of CA1,CA3 and molecular layer were lower in T2DM-MCI group(P=0.002,P=0.004,P=0.004,Bonfferroni correction).But there was no significant difference between T2DM-MCI group and MCI group(P>0.05/8,Bonferroni correction).Results of partial correlation analysis showed that the volumes of right hippocampal body and molecular layer body were positively correlated with RAVLT recall scores(r=0.471,P=0.042;r=0.518,P=0.023).4.Results of functional connectivity comparison showed that compared with MCI group,the functional connectivity of T2DM-MCI between right hippocampal body and right fusiform,right cerebellum crus I,left calcarine,right insula,right cuneus and right superior parietal lobe were increased.Moreover,compared with NC group,the connectivity of T2 DM group between right hippocampal body and left cerebellum 6 and right superior frontal lobe were significantly higher.Partial correlation analysis showed that the connectivity of T2DM-MCI group between right hippocampal body and right cerebellum crus I and left calcarine were negatively associated with RAVLT delayed recall score(r=-0.430,P=0.036;r=-0.58,P=0.003).Conclusion:The decline of epidosic memory of T2DM-MCI patients were significantly associated with the atrophies of right hippocampal body and the increased functional connectivity between right hippocampal body and right cerebellum crus I and left calcarine. |
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