Altered Brain Functional Connectivity Impairment Between Mild And Moderate Alzheimer’s Disease:a Rs-fMRI Study

Objective To explore the changes in alteration in brain network level and brain pair functional connectivity(FC)between patients with mild and moderate clinical Alzheimer’s disease(AD).Subjects and Methods 23 patients with mild AD,22 patients with moderate AD,and 25 normal control(NC)patients were selected for resting-state functional magnetic resonance imaging(rs-fMRI).MRI scanning was performed on the Trio Tim 3.0 T(Siemens Healthcare,Erlangen,Germany),MRI system with a 32-channel head coil.Resting-state f MRI data were collected using an echo planar imaging(EPI)sequence.Based on the whole brain f MRI data,The whole brain cortex was divided into 116 regions according to the automatic anatomical labeling(AAL)atlas.We identified whole brain functional connectivities by comparing the Pearson correlation coefficients of each pair of 116 regions.Six previously well-defined resting-state networks(RSNs)were extracted: the default mode network(DMN),the fronto-parietal network(FPN),the sensorimotor network(SMN),the occipital network(OCC),the cingulo-opercular network(CON),and the cerebellar network(CER).The altered FC at the brain network level and brain pair in mild AD and moderate AD were investigated.To obtain three groups of subjects 1)We investigated intra-network and inter-network connections in the subjects;2)The functional connectivity of each brain region was calculated.The differences in the brain network connectivity and brain FC were compared among the three groups by one-way ANOVA tests.If significant differences existed,a post-hoc t test was then performed for each two pairs of groups to further investigate the differences.Results 1)By one-way ANOVA analysis,there were significant differences among the three groups in intra-network connectivities within CER and DMN,and among between-network connections,especially in the DMN-linked and CER-linked inter-networks.The result of post-hoc t tests further showed that compared with the mild AD group,the inter-network connectivities within CER decreased sharply in the moderate AD group.The moderate AD group showed some degree of decreased connectivity in the CER-OCC pair and increased connectivity in the DMN-CON andCER-FPN pairs.P <0.05.2)ANOVA showed significant differences FC in posterior cingulated cortex(PCC),hippocampus and cerebellum among the three groups(p <0.05).The result of two-sample t tests showed that compared with the mild AD group,the moderate AD showed decreased connection within the cerebellum,increased FC between the bilateral hippocampus,and the increased FC between posterior cingulated cortex and orbital frontal cortex;Compared with the NC group,the mild AD showed connectivity in bilateral hippocampus increased,the connection within the cerebellum increased,the FC between PCC and the hippocampus decreased,orbital middle frontal cortex and part of the parietal lobe cortex decreased,p <0.05.Conclusion 1)This study demonstrated that the cerebellum-related network connections are more significantly changed in moderate AD than in mild AD.The alteration of brain network connectivity impairment provides new insight into the pathology of the progression of AD dementia.2)Moderate AD appears more severe brain functional connectivity abnormalities than mild AD and accompanied by the corresponding clinical symptoms,including abnormalities connections within the cerebellum,the posterior cingulated node related connection continued to reduce but weak compensatory,and increased in synchronicity of bilateral hippocampus.