The Research Of Cingulum Fiber Diffusivity And Resting-state Functional Connectivity Of Related Brain Regions In Alzheimer's Disease And Mild Cognitive Impairment

Purpose:To reseach the diffusion and functional connectivity abnormality of hippocampus-cingulum-cingulate cortex pathway in Papez circuit in MCI and AD patients, and study its relationship with clinical cognitive function for the early diagnosis of MCI and AD. To evaluate the value of DTI parameters pack in wihte matter micro-structure detection and study the inner connection between the functional connectivity strength and micro-stucture change of its connectionroute as the references in selecting DTI parameters and joint research of DTI and fMRI in related disease.Material and method:15 cases of AD,11 cases of MCI patients and 15 cases of normal cognition controls underwent routine T1WI, T2WI, FLAIR, T1_MPRAGE, DTI, EPI_BOLD scans using German Siemens Magnetom Trio Tim MR 3.0T MR scanner. Fractional Anisotropy(FA), Axial Diffusivity(DA) and Radical Diffusivity(DR) values of bilateral para_hippocampal regions of cingulum(PH_C), posterior dorsal curve of cinglum(PC_C) and anterior dorsal curve of cingulum(AC_C) were simultaneously measured in combination of tensor and T1_MPRAGE images on post processing workstation Syngo B17. Independent sample t-test, one_way analysis of variance(ANOVAs) with LSD and Dunnett's T3 were taken to compare the within_group and inter_group differences. The data was preprocessed through software Matlab 7.1, DPARSF_V2.0, SPM5, VBM and Rest_V1.4, which included slice timing, realign, normalize, smooth, detrend and bandpass filter(pass band0.01-0.08Hz). A mean time series for ROI was computed for reference time course, which was extracted out at a spherical region of interest (ROI)(radius=4mm) centered at a given coordinate(0,-53,26) within PCC. Cross correlation analysis was then carried out between the mean signal change in the PCC and the time series of every voxel of whole brain. Functional connectivity z_maps in rest were obtained after a Fisher's z transformamation, and at the same time the six head motion parameters, mean global signal, white matter and cerebrospinal fluid signals were removed as covariates. Next, the resting state default network maps within_group and functional connectivity abnormality maps inter_group were carried out though one_simple t_texts and two_sample t_texts. Then, functional connectivity maps between bilateral hippocampal and PCC were attained after input the bilateral hippocapal masks and AlphaSim correction. Finally, the correlation analysis and linear regression analysis were performed between the time series of abnormal regions and MMSE scores and correlated DTI parameter values of cingulum.Results:1.within_group analysis:no significant differences of bilateral cingulum in every patameter; MCI, AD groups and NC groups showed similar pattern of default networks, which included ventral MPFC, anterior cingulated cortex, visual cortex, hippocampus, cuneus/precuneus, PCC, middle and inferior temporal cortex 2.inter_group analysis:(1) MCI patients had significantly lower bilateral PH_C DA values, right PH_C DR value, and left PH_C FA value than controls; MCI patients showed decreased functional connectivity between right hippocapal and PCC compared with NC; (2) AD patients had significantly lower bilateral PH_C and PC_C DA values, bilateral PH_C and PC_C FA values, and higher bilateral PH_C and PC_C DR values than controls; AD patients showed decreased functional connectivity between bilateral hippocapal and PCC compared with NC;(3) AD patients had significantly lower bilateral PH_C and PC_C DA values, bilateral PH_C and PC_C FA values, and higher bilateral PH_C and PC_C DR values than MCI patients; 3.correlation analysis:(1)bilateral PH_C and PC_C DA values were positively correlated with MMSE scores(r=0.609/0.512,0.599/0.521, p<0.05); (2) bilateral PH_C DR values were negatively correlated with MMSE scores (r=-0.453/-0.428,p<0.05); (3) left PH_C and bilateral PC_C FA values were positively correlated with MMSE scores(r=0.627,0.641/0.533,p<0.05); functional connectivity between bilateral hippocapal and PCC was significantly correlated with MMSE scores(r=0.513,0.522,p<0.01).5.linear regression analysis:right PH_C DA values, PC_C DR values were contributed to functional connectivity of right hippocampus and PCC, and equation of linear regression was R_FC=0.047+0.556*R_PH_C_DA-1.160*R_PC_C_DR(R=0.671, R2=0.450); left PH_C DA values, PH_C DR values were contributed to functional connectivity of left hippocampus and PCC, and equation of linear regression was L FC=0.379+1.098*L PH C DA-1.105*L PH C DR (R=0.562, R2=0.315)Conclusion:1. the DTI and fMRI research of hippocampus-cingulum-cingulate cortex pathway in Papez circuit reflected the significance for MCI progressed to AD, and provided indexes in early diagnosis of MCI and AD.2.the cingulum is not the sole fiber connecting the hippocampus and PCC.3.DR and DA parameters pack is better than FA detecting the white matter microstructure alterations of MCI and AD patients.4.functinal connection strength within the DMN in resting state is significantly correlated with the micro-structure damage of its connectionroute.5. DA values of the damaged cingulum and functional connectivity which are significantly correlated with MMSE scores can be sensitive indicators evaluating the cognitive function of patients.