MRI Research Of Brain Structural And Functional Characteristics In Alzheimer Disease And Mild Cognitive Impairment

Mild cognitive impairment(MCI)is often an intermediate state between normal aging and dementia.The most common disease of dementia is Alzheimer's disease(AD).And that according to World Alzheimer Report 2015(http://www.alz.org),the incidence rate in recent years is continually increasing,especially MCI state.However,there are also considerate portions of MCI patients reverting to a normal functioning state when observed longitudinally,as well as those stopping deterioration into AD.These deviations in MCI patients may provide potentially useful information for early detection of AD.But there are fewer studies to explore the differentiation in brain structures and function of progressive MCI,even combined with risk genes.Thus,it need us developing related research to increase our understanding of the pathogenesis,and further looking for some reliable bio-markers to assist the clinical diagnosis for forecasting the development direction of MCI patients in coming years.In this study,we applied multimodal f MRI neuroimaging to investigate the abnormal brain structures and function of progressive MCI,and then to explore the modulation on brain gray matter activity and white matter integrity by APOE ?4 risk gene.The main results and innovations are as follows.Firstly,we focused on the correlation between low frequency f MRI signal fluctuations in the thalamus and those in all other brain regions in late stages of MCI,early stages of MCI and well-matched healthy controls.Then we employed a f MRI to examine alterations in functional connectivity(FC)of left/right fusiform gyrus comparing a MCI patients with age-matched control subjects.We found that the brain regions that showed significant differences were mainly located in the thalamo-related networks in late/early stages MCI and some crucial circuits related to fusiform are changed in amnestic MCI(a MCI).These two studies provided a new sight to understand the two important states of MCI and revealed resting-state f MRI is an appropriate method for exploring pathophysiological changes in a MCI.Secondly,we used amplitude of low-frequency fluctuation method to define the regions of interest(ROIs)which exhibited significant changes in a MCI compared with the control group.Then,we divided these ROIs into four networks in line with prior studies.The aim of this study is to explore the FC between these ROIs within networks and also to investigate the connectivity between networks.We found that several important FC strengthes showed different degrees of increase or decrease in the four networks in a MCI.The connection between the medial frontal cortex and hippo-campus and the connection between the supplementary motor area and middle temporal gyrus had remarkable positive correlations between FC values and MMSE scores.And that the default mode network has reduced inter-network connectivities with the sensorimotor and visual networks.These findings indicated that functional brain networks involved in cognition such as episodic memory,sensorimotor and visual cognition in a MCI were altered.Thirdly,MCI is often a transitional state between normal aging and AD.Progressively,some MCI patients convert to the AD state,some remain in the MCI state and some revert to a normal state.This study investigated effective connectivity features of the executive control network in progressive MCI groups and control group combined with ICA and GCA.Our findings revealed that these progressive MCI groups presented differentiated effective connectivity patterns of the executive control network.The differentiated effective connectivity patterns of the executive control network may be a potential bio-marker for early prediction of AD.Fourthly,the aim of this study is to identify potential bio-markers which can distinguish AD from cognitively intact elderly.We analyzed the rich club hierarchical structure of structural brain network between the AD group and control group based on two automated atlas atlases.The obtained features are fed to a linear discriminate analysis for classifying AD from cognitively intact elderly.The classification accuracy is superior as compared to the results obtained by using existing bio-markers.Our results suggest that the rich club hierarchical structure analysis is a valid tool for finding potential bio-markers.The obtained features can be employed as potential bio-markers for differentiating AD from cognitively intact controls.Fifthly,APOE ?4 allele is the genetic risk factor with the most established evidence for sporadic AD.Here,in a cognitively intact elderly group,we aimed to investigate the potential role of APOE ?4 in the modulation of grey matter activity,white matter integrity,and brain morphology before the development of clinically significant symptoms and signs,Our results revealed that anterior cingulate cortex and medial prefrontal cortex showed increased gray matter activity and precuneus showed decreased,and lower mean diffusivity in fibers of corona radiata and corpus callosum,Our results suggested that APOE ?4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions,even before any clinical or neuropsychic symtoms or signs of imminent disease.In conclusion,the relevant MCI studies and a series of research results found in this paper can help us better understand the pathogenesis of AD and MCI.These neuroimaging evidences and potential bio-markers we found could be refered by clinical researchers.However,there are also many deficiencies which need to be improved in future.