| PART Ⅰ.Resting-state cerebral neurovascular alterations predict mild cognitive impairment in patients with Stable Chronic Obstructive Pulmonary DiseaseObjective: Mild cognitive impairment in patients with chronic obstructive pulmonary disease(Chronic Obstructive Pulmonary Disease,COPD)is attracting more and more attention.The abnormalities of brain structure and function in patients with chronic obstructive pulmonary disease have been reported,but the changes of neurovascular coupling in patients with chronic obstructive pulmonary disease at rest have been rarely studied.Our study aims to characterize neurovascular coupling changes in patients with chronic obstructive pulmonary disease by using arterial spin labeling(arterial spin labeling,ASL)and blood oxygen level-dependent(blood oxygenation level dependent,BOLD)techniques.Methods: 1.Subjects A total of 85 subjects were recruited,including 45 patients with stable chronic obstructive pulmonary disease and 40 healthy controls,with age,sex and education matched.The sex,age and education level of all subjects and disease duration of patients were collected,and the pulmonary function test was also performed.The Montreal Cognitive Assessment scale(Mo CA)was used to evaluate the cognition of all patients with chronic obstructive pulmonary disease(COPD)and heathy controls.The Medical Research Council dyspnea scale(MRC)was used to quantify the degree of dyspnea.The severity of COPD was assessed according to The Global Initiative for Chronic Obstructive Lung Disease(GOLD).2.MRI scanning A GE MR750 3.0T magnetic resonance imaging scanner was used to acquire the MRI data,with an 8-channel phased array head coil.The subjects were instructed to relax,keep their eyes closed without thinking of anything in particular or falling asleep during scanning.And head was fixed with soft pads.Conventional MRI sequences include: T1-weighted sequence,T2-weighted sequence,diffusion-weighted sequence,T1-FLAIR sequence;those subjects with abnormalities in conventional MRI were excluded from the analysis.Functional MRI sequences include: blood oxygen level dependent,arterial spin labeling and T1 weighted Brain Volume(BRAVO).Two neuroimaging experts reviewed the routine sequence to rule out subjects with organic lesions.3.Data preprocessing and analysis Using SPM12,DPARSF,CAT12 and REST based on MATLAB 2014,the functional data were preprocessed,blood oxygen level dependent sequence was used to calculate degree centrality,and arterial spin labeling sequence was used to calculate cerebral blood flow.Then we use MATLAB programming program to calculate the correlation coefficient of cerebral blood flow and degree centrality,cerebral blood flow/degree centrality ratio,and compared the differences of degree centrality,cerebral blood flow,correlation coefficient of cerebral blood flow and degree centrality and cerebral blood flow/degree centrality ratio between the two groups.4.Statistical Analysis Two-sample t test was used to analyze the differences of age,education,pulmonary function parameters and Montreal cognitive score between the two groups by using SPSS 21.0 software,and the gender differences between the two groups were tested by Chi-square test.Two-sample t-test of REST 1.8 software was used to analyze the differences of cerebral blood flow,degree centrality,cerebral blood flow-degree centrality correlation coefficient and cerebral blood flow/degree centrality between the two groups,with age,gender and educational level as covariates.The brain regions with statistically significant differences in cerebral blood flow,degree centrality(FDR correction)were obtained,and the coordinates of the peak values of these brain regions were extracted in Montreal Neurological Institute(MNI)space.The correlation analysis method of SPSS software was used to evaluate the correlation among cognitive score,pulmonary function parameters and function data.Results: 1.The results of clinical data showed that there was no significant difference in age,sex,educational level and BMI between the chronic obstructive pulmonary disease group and the healthy control group(P=0.465,0.609,0.509,0.667).The Mo CA scores and sub-cognitive domain(visual space/executive function,naming,attention,language,abstraction,delayed recall,orientation)in the chronic obstructive pulmonary disease group were lower than those in the healthy control group(all P<0.001).The pulmonary function parameters in patients with chronic obstructive pulmonary disease were significantly lower than those in healthy controls(all P<0.001).2.Intergroup differences of functional data and correlational analysis Compared with the healthy control group,chronic obstructive pulmonary disease group showed significantly decreased cerebral blood flow in bilateral dorsolateral prefrontal lobe,left superior marginal gyrus and bilateral anterior cingulate gyrus;the brain regions with increased centrality in patients with chronic obstructive pulmonary disease were mainly located in the left supramarginal gyrus and left precentral gyrus.Using REST software,the brain regions with significantly different cerebral blood flow and degree centrality were fused into four brain regions,which were located in the left precentral gyrus/dorsolateral prefrontal lobe,the right dorsolateral prefrontal lobe,the left supramarginal gyrus and bilateral anterior cingulate gyrus.The cerebral blood flow correlated with the degree centrality in four brain regions of chronic obstructive pulmonary disease and healthy control group,but no significant difference was found in the correlation coefficient of cerebral blood flow and degree centrality between the two groups.Voxel-by-voxel analysis showed that the cerebral blood flow/degree centrality ratio in some brain regions of patients with chronic obstructive pulmonary disease was significantly higher than that of healthy controls,mainly located in bilateral medial prefrontal lobe(ventromedial prefrontal lobe,orbitofrontal lobe,rectus gyrus),bilateral caudate nucleus,left middle temporal gyrus(parahippocampal gyrus and fusiform gyrus)and left lingual gyrus(q<0.05,FDR correction).There was no correlation between abnormal cerebral blood flow and clinical symptoms in patients with chronic obstructive pulmonary disease(P>0.05).There was a negative correlation between the degree centrality of left supramarginal gyrus and the score of visual space / executive function in patients with chronic obstructive pulmonary disease(r = 0.515,P<0.001).There was a negative correlation between the cerebral blood flow/degree centrality ratio of left lingual gyrus and naming function in patients with chronic obstructive pulmonary disease(r = 0.709,P < 0.001).The cerebral blood flow/degree centrality ratio of left medial frontal lobe/temporal lobe in patients with chronic obstructive pulmonary disease was positively correlated with Montreal cognitive assessment score(r = 0.485,P=0.001),visuospatial/executive function score(r = 0.646,P <0.001)and delayed recall score(r = 0.468,P= 0.001).Conclusion: Using the combinational method of resting-state arterial spin labeling and blood oxygen level-dependent techniques,we analyzed the changes of cerebral blood flow and degree center coupling in patients with chronic obstructive pulmonary disease,and made a comprehensive analysis of the brain network of chronic obstructive pulmonary disease.Abnormal neurovascular coupling was found in cognitive-related brain areas in patients with chronic obstructive pulmonary disease.And neurovascular coupling abnormalities of several brain regions were correlated with cognitive function and sub-domain dysfunction such as visuospatial/executive,delayed recall and naming.We found the potential neural pathogenesis of mild cognitive impairment in patients with chronic obstructive pulmonary disease,which might eventually help to study the early detection and early intervention of cognitive impairment in patients with chronic obstructive pulmonary disease,and improve the quality of life and therapeutic effect of chronic obstructive pulmonary disease.PART Ⅱ Alterations of grey matter volumes and network-level functions in patients with stable Chronic Obstructive Pulmonary DiseaseObjective: Chronic obstructive pulmonary disease,with a high prevalence rate,can aggravate the incidence of mild cognitive impairment,but it has not attracted clinical attention.The first part of this study also confirmed the abnormal neurovascular coupling in patients with chronic chromatic lung disease during resting state.Some brain regions are involved into cognitive impairment and some cognitive functions.However,it is not clear whether there are abnormalities in gray matter structure and related brain regions in patients with chronic obstructive pulmonary disease(COPD).Up to now,the researches on the structural changes of gray matter in chronic obstructive pulmonary disease mainly performed by using single method or multiple methods to analyze respectively.In this study,the alterations structure and function in patients with stable chronic obstructive pulmonary disease were investigated by using voxel-based morphological analysis and seed-based resting-state functional connectivity analysis.Furthermore,the relationship between these alterations and pulmonary function,cognitive function and disease duration were also explored in patients with chronic obstructive pulmonary disease.Methods: 1.Subjects 45 patients with stable chronic obstructive pulmonary disease and 40 age,sex and education-matched healthy controls were recruited to participate in this study.The sex,age,education level of all subjects and disease duration of all patients were collected,and the pulmonary function test was also performed.The Montreal Cognitive Assessment scale(Mo CA)was used to evaluate the cognition of all patients with chronic obstructive pulmonary disease and healthy controls.The Medical Research Council dyspnea scale(MRC)is used to quantify the degree of dyspnea of patients.The severity of patients with chronic obstructive pulmonary disease was assessed using the Global Initiative for chronic obstructive Pulmonary Disease(GOLD).2.MRI scanning GE MR750 3.0T magnetic resonance imaging scanner with an 8-channel phased array head coil was used to collect MRI data.The subject’s head was fixed with soft pads.Routine sequences(T1WI,T2 WI,T2-FLAIR),blood oxygen level-dependent and T1-weighted Brain Volume data were acquired.Those with brain abnormalities found in routine sequence were excluded from the group.3.Data preprocessing and analysis MATLAB,SPM and CAT12 were used to process T1-weighted Brain Volume data;and DPABI,DARSFA and REST software were used to process the resting oxygen level-dependent data.3.Statistical analysis The difference of gray matter volume between the two groups was analyzed by using REST software(age,sex,educational level and total intracranial volume as covariables).The peak Montreal Neurological Institute(MNI)spatial coordinates of these brain regions were extracted,and the differential brain regions were used as seeds to analyze the functional connectivity of the rest whole brain.The correlations between the data of clinical symptoms,cognitive function and gray matter volume of altered brain regions,seed-based functional connectivity.The differences of age,education level and clinical symptom scores between the two groups were analyzed by using SPSS 18.0 statistical software,and the gender differences between the two groups were tested by using Chi-square test.Results: 1.The statistical results of clinical data showed that there was no significant difference in age,sex,educational level and BMI between the chronic obstructive pulmonary disease group and the healthy control group(P=0.465,0.609,0.509,0.667).The scores of Mo CA and cognitive sub-domain(visual space/executive function,naming,attention,language,abstraction,delayed recall,orientation)in the chronic obstructive pulmonary disease group were lower than those in the healthy control group(all P <0.001).The pulmonary function parameters of patients with chronic obstructive pulmonary disease were significantly lower than those in healthy controls(all P< 0.001).2.Two sample t test analyses of the difference in gray matter volume and seed-based functional connectivity between the two groups were performed.Compared with the healthy control group,the patients with chronic obstructive pulmonary disease showed decreased gray matter volume mainly in the left supramarginal gyrus/precentral gyrus,bilateral posterior middle cingulate gyrus,right middle occipital gyrus and right supramarginal gyrus.Taking the brain regions with altered gray matter volume as seeds,the voxel-by-voxel functional connectivity analyses showed disrupt functional connectivity within the visual network and frontal-parietal network in patients with chronic obstructive pulmonary disease.3.Correlation analysis showed that visual network and frontoparietal network dysfunctions in patients with chronic obstructive pulmonary disease were positively correlated with Montreal cognitive assessment score,language domain score,attention domain score and disease duration.Conclusion: In this study,voxel-based morphological analysis and seed-based functional connectivity analysis were used to investigate the structural and functional alterations in patients with stable obstructive pulmonary disease.We found that there were abnormalities in gray matter volume of some brain regions in patients with chronic obstructive pulmonary disease.Further functional connectivity analysis shows functional alterations at the regional and network level within visual networks,frontal-parietal networks,and other networks.We speculate that the alterations of gray matter volume and functional connectivity of the visual network and the frontoparietal network may contribute to the neural mechanism of mild cognitive impairment in patients with stable chronic obstructive pulmonary disease.PART Ⅲ A Study on the relationship between mild cognitive impairment and structural-functional alterations in patients with chronic obstructive pulmonary diseaseObjective: To evaluate the correlation between cognitive impairment and brain structural-functional alterations in patients with chronic obstructive pulmonary disease(COPD).Methods: 63 patients with stable chronic obstructive pulmonary disease and 34 healthy controls were enrolled in this study.All subjects underwent cognitive function assessment and functional magnetic resonance imaging(f MRI)scanning.Pulmonary function test and blood gas analysis were performed.The cognitive function of all subjects was evaluated by using Mo CA scale.According to the score of Mo CA,the patients with chronic obstructive pulmonary disease were divided into two groups: chronic obstructive pulmonary disease with mild cognitive impairment(COPD-MCI)and chronic obstructive pulmonary disease with normal cognitive function(COPD-n MCI).Taking age,sex and education level and total intracranial volume as covariables,the differences of gray matter volume among COPD-MCI,COPD-n MCI and healthy control group were compared by analysis of covariance and post-hoc pairwise analysis.The resting-state functional connectivity of regions with gray matter volume difference were calculated,and the differences among the three groups were compared too.The gray matter volume and functional connectivity of these brain regions were extracted from each patient with chronic obstructive pulmonary disease,and the correlation with the disease duration,pulmonary function test and cognitive function was further analyzed.Results: Among the 63 patients with chronic obstructive pulmonary disease,33 patients with chronic obstructive pulmonary disease were with mild cognitive impairment(33/63,52.40%)and 30 patients were with normal cognitive function(30/63,48.45%).In the COPD-n MCI group and healthy control group,the scores of cognitive function assessment were all in the normal range.The scores of Mo CA and the five cognitive sub-domains in COPD-MCI were lower than those in COPD-n MCI and healthy controls.In addition,taking sex,age and education level as covariables,the results of covariance analysis showed that there were significant differences in gray matter volume in bilateral lingual gyrus,left middle temporal gyrus,left thalamus,left postcentral gyrus/inferior parietal lobule and right dorsolateral prefrontal lobe among the three groups.In the post-hoc pairwise comparisons,the COPD-MCI group showed lower gray matter volume in the left thalamus than that in the COPD-n MCI group,and lower gray matter volume in the bilateral lingual gyrus,left middle temporal gyrus,left thalamus,left postcentral gyrus/inferior parietal lobule and right dorsolateral prefrontal lobe than those in the healthy control group.The gray matter volume in the left postcentral gyrus/inferior parietal lobule in the COPD-n MCI group was lower than that in the healthy control group.Taking the six brain regions as seeds,the resting-state functional connectivity between the six seeds and the rest whole brain voxels in each subject were calculated.Age,sex and education level were taken as covariates.ANCOVA analysis showed that the differences of the functional connectivity between bilateral lingual gyrus and right lingual gyrus/fusiform gyrus,functional connectivity between the left precentral gyrus/inferior parietal lobule and bilateral precuneus and left supramarginal gyrus,functional connectivity between right dorsolateral prefrontal gyrus and left caudate nucleus were statistically significant among the three groups.Correlation analysis showed that the grey matter volume of the left thalamus in the patients with chronic obstructive pulmonary disease was positively correlated with the Mo CA score,visuospatial/executive function and naming.Conclusion: There were significant differences in the gray matter volume of bilateral lingual gyrus,left middle temporal gyrus,left thalamus,right supramarginal gyrus,left postcentral gyrus/ inferior parietal lobule and right dorsolateral prefrontal lobe among COPD-MCI,COPD-n MCI and healthy controls.In addition,the functional connectivity of bilateral lingual gyrus,left postcentral gyrus/inferior parietal lobule and right dorsolateral prefrontal lobe were also different significantly.And the left thalamus plays an important role in cognitive function in patients with chronic obstructive pulmonary disease,which may be involving into the neural mechanism of cognitive impairment in patients with chronic obstructive pulmonary disease. |
PDF Full Text Request