Alterations Of The Default Mode Network Of Resting-state Functional Magnetic Resonance Imaging And Cognitive Impairments In Patients With Chronic Obstructive Pulmonary Disease

Objectives:To evaluate the cognitive function of Chronic obstructive pulmonary disease patients.Using the resting state functional magnetic resonance imaging,we aim to explore the neural mechanisms of cognitive impairment in COPD patients by comparing the functional connectivity of normal control subjects and COPD patients in different grades.Meanwhile,we also investigate the correlations between cognitive function scores and neuroimaging datum or clinical datum.Materials and methods:From October 2014 to February 2016,a total of 113 subjects meet the criteria were recruited,which included 30 normal subjects,29 mild,30 moderate and 24 severe COPD patients.The cognitive function were measured by Montreal Cognitive Assessment（Mo CA）and digital span test.All subjects complete the pulmonary function test and part of them complete the arterial blood gas tests.All subjects received the resting state functional magnetic resonance imaging test using 3.0-T MRI scanner with a 16-channel head coil,and the functional connectivity of default mode network of all subjects were analysed with seed-based correlation analysis.Finally the correlations of cognitive function scores and neuroimaging or clinical datum were also analysed by Pearson’s correlation analysis.Results:1.There were about 58 percent COPD patients got cognitive impairment,which mainly manifested in executive function,attention,delayed recall,abstraction and orientation.The cognitive function scores were significantly different between COPD patients and normal control subjects,meanwhile,we found the cognitive impairment were worsened with the degree of airflow obstruction.Group comparison analyses revealed that compared with normal control subjects,the mild COPD patients got significantly different Mo CA score and reverse memory span score.The Mo CA score,executive function,attention,delayed recall,abstraction,digital memory span score,and reverse memory span score of moderate COPD patients were obviously different from normal control subjects.The Mo CA score,executive function,attention,delayed recall,orientation,digital memory span score,and reverse memory span score of severe COPD patients were obviously different from normal control subjects.When compared with mild COPD patients,the severe COPD patients got significantly different Mo CA score,executive function and orientation,and the Mo CA score of moderate COPD patients was significantly different from mild ones.The Mo CA score of severe COPD patients was significantly different from moderate ones.Pearson’s correlation analysis revealed that the Mo CA score of COPD patients were positively correlated with PaO₂ and FEV1,but not Pa CO2.FEV1 was positively correlated with PaO₂,while negatively related with Pa CO2.2.Compared with normal control subjects,The activated brain regions of DMN in the three groups of COPD patients were declined,which we can conclude that the activated areas of DMN in the severe COPD patients were significantly lower than other three groups.Compared with normal control subjects,the functional connectivity values of default-mode network in COPD patients were declined and varied with the pulmonary function parameter FEV1.The functional connectivity values of some brain regions of default-mode network represent by the left posterior cingulate cortex and left hippocampus were declined with the decreased pulmonary function,especially in severe COPD patients.However,the functional connectivity values of right parahippocampus and right-rolandic operculum were increased with the decreased pulmonary function,especially in moderate COPD patients.3.The functional connectivity values of default-mode network among the four groups were significantly different in the following six brain regions,which were the left posterior cingulate cortex,left anterior cingulated cortex,left supramarginal cortex,left hippocampus,right parahippocampus and right medial orbitofrontal cortex respectively.4.Pearson’s correlation analysis revealed that the Mo CA score of COPD patients were positively correlated to the functional connectivity values of left posterior cingulate cortex and left hippocampus,the visuospatial executive function score was positively related to the functional connectivity values of left posterior cingulate cortex and left hippocampus while negatively related to the functional connectivity value of left supramarginal cortex;meanwhile,the naming function score was negatively related with the functional connectivity value of right parahippocampus,and the orientation score was positively related to the functional connectivity value of right medial orbitofrontal cortex.The functional connectivity values of left anterior cingulated cortex,left posterior cingulate cortex,left hippocampus and right medial orbitofrontal cortex were all positively related to FEV1.Conclusions:COPD patients have cognitive impairment,which mainly manifested in executive function,attention,delayed recall,abstraction and orientation.The cognitive impairment is correlate with the pulmonary function and PaO₂.The changes of functional connectivity in activated brain regions of default-mode network may predict the cognitive impairment of COPD patients.The left posterior cingulate cortex and left hippocampus in default-mode network maybe the important brain regions that related to the cognitive impairment of COPD patients.The brain function of COPD patients possibly have the ability to compensate,and this ability maybe the strongest in moderate COPD patients,while the severe COPD patients may lose this ability as a result of decompensation.The function of the default-mode network of COPD patients maybe imbalanced and this maybe the neural mechanisms of cognitive impairment in COPD patients.Hypoxia and the decreased lung function maybe an important pathophysiological mechanism that lead to the functional changes of default-mode network,as well as the cognitive impairment of COPD patients.