Study Of Mild Cognitive Impairment And Alzheimer’s Disease By Resting-state Functional Magnetic Resonance Imaging

Objective: To discover the differences and characteristics of default mode network andfunctional connectivities of the whole brain among AD, MCI patients and the healthy oldcontrol by BOLD-fMRI resting imaging technology. Meanwhile, combined withneuropsychological analysis to expolre the appilication of BOLD-fMRI resting imagingtechnology in this study and provide the evidence of the early diagnosis of AD and MCI.Methods: AD and MCI patients were collected from the neurology department offaculty of medicine of Shimane University in Japan. All the patients were sured diagonosedby neurologists according to the internationally recognized diagnostic criterias andneuropsychology scoring criterias.Finally14AD patients and17MCI patients were ensured.And17old healthy controls were selected from the Japanese health examination center. Theage, gender and education level were matched with the groups of the patients. MRI dataacquisition was performed on a SIMEMNS Trio3-Tesla scanner. Independent componentanalysis on default mode net work, intrinsic functional connectivity analysis and seed-basedanalysis of the whole brain were performed in data processing, in order to compare thedifferences of the functional connectivity in the brain within and among the three groups.Results:Part I: Neuropsychological assessment1. AD group, the MCI group and HC group in age, gender, level of education has nosignificant difference (P>0.05).2. AD group, the MCI group and HC group on SDS score has no significant difference (P>0.05), the other scale examination score (MMSE, FAB, verbal fluency test, apathy score)had statistically significant difference (P <0.01) among the three groups.Part II: Resting state functional magnetic resonance imaging analysis1.Combine Default mode network and Independent component analysis together to dealwith the image showed as following, inside default mode network, the activate area andextend of group AD were all lower than group HC, especially in limbic lobe. While there wasno much difference between group AD and group MCI on the activation and extend ofregions in default mode network, especially Post Cingulate Gyrus, but compare it with groupMCI, group AD appeared a little weaker. Through the different slices of DMN imagesshowing, we could know the strong and weak region clearly.2. Functional connectivity analysis was used.2.1It shows the result as following, in contrast of all the functional connectivity of thewhole brain, there is a significant statistical difference between the groups of patients and HCgroup. The significant regions were limbic lobe, precuneus, Posterior cingulate, Parietal,calcarine sulcus, Corpus Callosum, Angular Gyrus, Inferior Parietal lobule, Frontal lobe,Occipital lobe, Precentral Gyrus, Brodmann4district. With the default network coverage, andfurther analysis of the significant difference between the derived group of brain regions of theleft Angular Gyrus the Brodmann39, Corpus Callosum, and the result has a linear correlationwith the MMSE score(P <0.01).2.2Seed-based analysis: The left and right hippocampus in the brain of the AD groupshowing no statistically significant positive activation（P>0.05）, the right hippocampus andthe left precuneus showing significant negative activation related（P<0.05）, which was verydifferent fromMCI and HC groups.Only in HC group there was significant positive activation（P<0.05）between PCU and PCC. In all3groups MPFC still not connected with other seedregions.2.3Intrinsic connectivity contrast: The regions contain functional connectivity of the group AD were weaker than the group MCI in cerebellum areas; the regions are stronger thangroup MCI was in Precentral_L; The regions contain functional connectivities of group MCIwere weaker than group HC: Caudate_L, olfactory_L, precuneus_L, precuneus_R,Temporal_Pole_Sup_L, Parietal_Inf_R, most of which were concluded in DMN; The regionscontain functional connectivity of group MCI were stronger were Cingulum, Cerebelum,insular_L; The regions contain functional connectivity of group AD were weaker than groupHC: Insula_R, Temporal_Pole_Sup_R; The regions contain functional connectivity of groupAD were stronger than group HC: Frontal_Inf_Tri_L and CerebellarTonsil.2.4Seed-voxel analysis：①MPFC (Medial preFrontal cortex): The regions containfunctional connectivity of group AD were weaker than group MCI in MPFC: Cerebellum,AnteriorLobe, Temporal_Pole_Mid_L, Parahippocampal_R; The regions contain functionalconnectivity of group AD were stronger than group MCI in MPFC: Cerebellum PosteriorLobe, Frontal_Sup_Medial_L, Hippocampus_L; The regions contain functional connectivityof group MCI were weaker than group HC in MPFC: Frontal_Sup_L, Temporal_Mid_L,Frontal_Sup_Orb_R; The regions contain functional connectivity of group MCI were strongerthan group HC in MPFC: Frontal_Inf_Orb_L, Culmen, Insular_L, Precentral Gyrus; Theregions contain functional connectivity of group AD were weaker than group HC in MPFC:Frontal_Sup_R, Postcentral_L, Middle Temporal Gyrus, Superior Temporal Gyrus,Precentral_R; The regions contain functional connectivity of group AD were stronger thangroup HC in MPFC: Rectus_R, Frontal_Sup_Orb_R, Cerebelum, Frontal_Mid_L;②LLP(left lateral Parieta): The regions contain functional connectivity of group AD were weakerthan group MCI in LLP: Calcarine_L, Cuneus_R, Lingual, Occipital_Mid_L; The regionscontain functional connectivity of group AD are stronger than group MCI in LLP:Temporal_Mid_L, Cerebelum; The regions contain functional connectivity of group MCIwere weaker than group HC in LLP: Precuneus, Frontal_Sup_Orb_L, Frontal_Sup_Orb_R,Temporal_Mid_L, Angular_R, Parietal_Sup_L, Parietal_Inf_L; The regions contain functional connectivity of group MCI were stronger than group HC in LLP: Occipital_Mid_L,Temporal_Sup_R, Cuneus_L, Frontal_Sup_L, Temporal_Mid_R, Frontal_Mid_R; Theregions contain functional connectivity of group AD were weaker than group HC in LLP:PreCuneus, Lingual_R, Parahippocampal_L, Cerebelum, Fusiform_R, Temporal_Mid_L,Postcentral_L, Temporal_Mid_R, Frontal_Mid, Caudate_L; The regions contain functionalconnectivity of group AD were stronger than group HC in LLP: Temporal_Sup_R,Cingulum, Temporal_Mid_L, Temporal_Inf_R, Frontal_Mid_R.③PCC (Posterior cingulatecortex): The regions contain functional connectivity of group AD were weaker than groupMCI in PCC: PreCuneus, Calcarine_L; The regions contain functional connectivity of groupAD were stronger than group MCI in PCC: Calcarine_L, Cerebelum, Postcentral_L,Cingulum, The regions contain functional connectivity of group MCI were weaker than groupHC in PCC: Cingulum_Mid_L, Angular_L, Supramarginal Gyrus, Parietal_Inf_L, CorpusCallosum; The regions contain functional connectivity of group MCI are stronger than groupHC in PCC: Calcarine_L, Lingual_L, Occipital_Mid_R, PreCuneus, Parietal_Sup_L,Cuneus_L, PreCuneus_R, Temporal, Occipital_Sup_R; The regions contain functionalconnectivity of group AD were weaker than group HC in PCC: Postcentral_L, Angular_R,The regions contain functional connectivity of group AD were stronger than group HC inPCC: Cerebelim, Calcarine_L；④HIPR：(right hippocampus), The regions contain functionalconnectivity of group AD were stronger than group MCI in HIPR: Frontal_Sup,Frontal_Mid_L, Rectus_R, Olfactory_L; The regions contain functional connectivity of groupAD were weaker than group MCI in HIPR: Cerebelum_Crus；The regions contain functionalconnectivity of group MCI were weaker than group HC in HIPR: Temporal_Sup_R,Cerebelum; The regions contain functional connectivity of group MCI were stronger thangroup HC in HIPR: PreCuneus_R, Supp_Motor_Area_R, Cuneus_R, Parahippocampal_R,Frontal_Sup Occipital_Mid_R, Lingual_R, Occipital_Mid_R, Temporal; The regions containfunctional connectivity of group AD were weaker than group HC in HIPR: Temporal_Mid_R, Fusiform_R, Cerebelum, Putamen_L; The regions contain functional connectivity of groupAD were stronger than group HC in HIPR: Supp_Motor_Area_R, Temporal_Inf_R,Parietal_Inf_L, Postcentral_L, Occipital_Mid_L, Parietal_Inf_R.⑤HIPL (left hippocampus):The regions contain functional connectivity of group AD were weaker than group MCI inHIPL: Precentral_R, Postcentral_R, Occipital_Mid_L, Frontal_Mid_L, PreCuneus_R,Temporal_Mid_R, Frontal_Sup_Medial_L; The regions contain functional connectivity ofgroup AD were stronger than group MCI in HIPL: Hippocampus_L, Cingulum_Post_L,Frontal_Mid_L, Precuneus_R, Temporal_Inf_R, Postcentral_R; The regions containfunctional connectivity of group MCI were weaker than group HC in HIPL: Precuneus_L,Cingulum_Post_L, Cerebelum, Caudate_L; The regions contain functional connectivity ofgroup MCI were stronger than group HC in HIPL: Parahippocampal_L, Frontal_Mid_L,Frontal_Sup_Medial_R, Temporal_Mid_L, Caudate_R; The regions contain functionalconnectivity of group AD were weaker than group HC in HIPL: Temporal_Mid_R,Postcentral_R, Parahippocampal_R, Hippocampus_R; The regions contain functionalconnectivity of group AD were stronger than group HC in HIPL: Temporal_Mid_L, CorpusCallosum, Parahippocampal_L.Conclusions: Alzheimer’s disease patients and mild cognitive impairment patientscompared with normal aging, there might exist some abnormal functional connectivitybetween the3groups in partly brain regions and areas, such abnormalities may have a certainrelationship with cognitive dysfunction. In our study the combined application ofneuropsychological and resting state functional magnetic resonance imaging will provide animportant basis for the early diagnosis of dementia.