Abnormality Of Interhemispheric Structural-and Functional-Connections Associated With Alzheimer’s Disease And Mild Cognitive Impairment

Many studies have shown that callosal fiber tract damage in Alzheimer’s disease(AD)causes problems with interhemispheric information communication and coordination of activities.The degree of structural integrity damage of the corpus callosum is closely related to the degree of altered interhemispheric functional connectivity and cognitive dysfunction,but the patterns and intrinsic mechanisms of interhemispheric structural and functional changes in AD are still unclear.The purpose of this study is to explore interhemispheric structural connectivity and functional connectivity abnormalities in Alzheimer’s disease(AD)and mild cognitive impairment(MCI)and their relationship with cognitive function and activities of daily life by using transcallosal tract template(TCATT)and automatic anatomical labeling gray matter template(AAL).The main contents of this study are as follows:Part Ⅰ.Inter-hemispheric structural connectivity abnormalities in AD and MCI and their relationship with cognitive function and activities of daily living.MR diffusion tensor imaging data of 23 AD patients,47 MCI patients and 37 healthy controls(HCs)were collected.Using the TCATT template,the fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(DA)and radial diffusivity(RD)of 32 transcallosal tracts connecting the interhemispheric homologous brain areas(including the prefrontal lobe,sensory motor area,parietal lobe,temporal lobe and occipital lobe)among the three groups were calculated and compared.Water diffusion index values(FA,MD,RD and DA)of transcallosal tracts to the different homologous brain regions between the AD and MCI groups were further correlated with the basic scale of Montreal Cognitive Assessment(Mo CA＿B)and the scale of Activities of Daily Living Scale(ADL).The results showed that compared with the HC group,the mean values of the four diffusion indicators were significantly changed in the AD group,but only the mean DA values of eight dorsolateral fibers were different significantly in the MCI group(P<0.05,FDR corrected).Compared with the MCI group,the mean values of three diffusion index(FA,MD,and RD)for the majority of transcallosal nerve fibers(except to the prefrontal lobe)in the AD group were different significantly(P<0.05,FDR corrected).In the AD group,the mean values of four diffusion index in the transcallosal tracts were not significantly correlated with Mo CA＿B scores,but the mean values of three diffusion index(FA,MD,and RD)were significantly correlated with the ADL scores(P<0.05,FDR correction).In the MCI group,the mean DA values in a small number of transcallosal tracts were significantly correlated with the Mo CA＿B scores(P<0.05,FDR correction).Part Ⅱ.Inter-hemispheric functional connectivity abnormalities in AD and MCI and their relationship with cognitive function and activities of daily living.The same subjects of Part I were further studied and their resting-state f MRI data were collected.Based on the automated anatomical labeling(AAL),the 32 pairs of homologous brain regions corresponding to the TCATT template were saved as the ROI,functional connectivity(FC)values in the corresponding interhemispheric brain regions(including prefrontal lobe,sensory motor area,parietal lobe,temporal lobe and occipital lobe)among the three groups were calculated and compared.FC values in the different homologous brain regions between the AD and MCI groups were further correlated with the basic scale of Montreal Cognitive Assessment(Mo CA＿B)and the scale of Activities of Daily Living Scale(ADL).The results showed,compared with HC group,the mean FC values of homologous brain regions(including the inferior parietal lobule and middle temporal gyrus)in the AD group decreased significantly;the mean FC values of twenty-one homologous brain regions increased significantly,but one in the superior frontal gyrus decreased significantly in the MCI group(P< 0.05,FDR corrected).Compared with the MCI group,the mean FC values of twenty-two homologous brain regions decreased significantly,but one in the superior frontal gyrus increased significantly in the AD group(P<0.05,FDR corrected).Furthermore,there were significant negative correlations between FC values in the middle occipital and superior temporal gyrus and ADL scores in the AD group(P<0.05,FDR correction).In conclusion,by using advanced magnetic resonance imaging technology(diffusion tensor imaging and resting-state functional magnetic resonance imaging)and combining with high-resolution fine atlas of callosal fiber tract,this paper investigated the changes of the interhemispheric callosal fiber bundle microstructure and its corresponding interhemispheric functional connectivity in a relatively large samples of three groups(AD,MCI and HCs).The results showed that AD has more severe and extensive interhemispheric structural connectivity damage than MCI;especially,the degeneration of callosal fiber bundle is closely related to the decline of daily living activities,suggesting that the severity of microstructural damage of corpus calloal fiber bundles may be used as an important reference index to evaluate the ability of life activity in AD.On the other hand,functional connectivity increased significantly in most homologous brain regions in MCI,while functional connectivity in almost all the homologous brain regions in AD were not significantly different from the HCs,perhaps implying that the interhemispheric functional connectivity changes in homomic brain regions can be used as an important reference to distinguish MCI from AD,providing a new way for exploring the interhemispheric structural and functional changes of neurodegenerative diseases,such as AD and MCI.