A Study On Brain Structure Change And Its Correlation With Cognitive Impairment In Patients With Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease（COPD）is a common,preventable and treatable condition characterized by respiratory symptoms and restricted airflow due to airway and/or alveolar abnormalities,which is not fully reversible and progressive,and usually associated with servere exposure to toxic particles and gases.With the development of science and technology,we have deep understanding about COPD and the treatment for it was more comprehensive.As we know,patients with COPD not only have sustained irreversible impairment of lung function,but also have cognitive impairment to a certain extent,which can affect the course and prognosis of the disease.The current study found that cognitive impairment exists not only in the acute exacerbation of COPD patients,but also persists in the stable phase,,but the relevant mechanisms remain unclear.Numerous studies have focused on the study of hypoxia and the mechanismsof related injury.With the development of multi-modal magnetic resonance imaging techniques,we can investigate the details of the gray matter and white matter,and help us know related neural mechanisms.At present,there are relatively few stratified analysis studies on COPD based on lung function,and the mechanism of its influence on cognitive impairment of COPD is still unclear,and the research on related neural mechanisms is particularly rare.With the development of multiparametric MR imaging techniques,it is possible for us to study the detail of the brain structure and function.If we can find the neural basis of cognitive impairment in patients with COPD,it will have clinical significance to help prevent and change the cognitive level of COPD patients.ObjectiveTo explore the influencing factors and possible neural mechanisms of COPD cognitive function impairment by a combination of cognitive function assessment and multimodal MRI imaging.（1）To explore the characteristics of cognitive impairment in COPD patients and its relation with pulmonary function and related clinical signs.（2）To explore the characteristics of gray matter structure changes in COPD patients,and its relation with cognitive function and lung function.（3）To explore the characteristics of white matter structure changes in COPD patients,and its relation with cognitive function and lung function.Methods（1）Research 1:Thirty-one people were included in the normal control group,29 in the mild COPD group,29 in the moderate group and 26 in the severe group.Cognitive function was assessed with Montreal Cognitive Scale（MoCA）Beijing Version and Digital Wide Memory Scale（DBMS）.Pulmonary function and arterial oxygen were measured.The differences between COPD groups and control groups were analyzed.Age,sex,education level,body mass index,smoking status and smoking index were used as covariate.Partial correlation analysis was made between cognitive score and the parameters of arterial oxygen and pulmonary function.（2）Research 2:Three-dimensional high-resolution T1 structure images were aquired,and the density of gray matter in both COPD groups and control group were mesured on voxel based morphology（VBM）.Partial correlation analysis was made between the gray matter density and MoCA scores/FEV1.（3）Research 3:Data of diffusion tensor imaging were collected and the changes of white matter microstructures in COPD group and control group were obtained by TBSS method.Partial correlation analysis was made between the imaging parameters（MD,AD or RD）and clinical variables（MoCA scores and FEV1）.Results（1）Research 1:There is great difference in the total score of MoCA among the four groups,especially between the severe group and the mild group,between the moderate group and the mild group,and there was a statistical difference between the mild group and the control group（P<0.05）,but s no significant difference was found between the moderate and severe groups.Great differences exsited in visual function,attention,abstraction,delayed recall,orientation and digital memory span scores（total scores and backs）among the four groups（P<0.05）.Correlation analysis showed that there was a slight positive correlation（r=0.259,P=0.021;r=0.224,P=0.047）between the total score of MoCA and pulmonary function（FEV1）and PaO₂,but there was no significant correlation between the total score of MoCA and SaO₂.（2）Research 2:Compared with control,there is extensive atrophy of gray matter in bilateral orbital part of the inferior frontal gyrus,left superior frontal gyrus,middle frontal gyrus,medial orbital gyrus,parahippocampal gyrus/fusiform gyrus,auxiliary motor cortex and right thalamus in COPD groups,but no significant difference in gray matter density in mild COPD group.The decreased area of grey matter density in moderate COPD group is relatively small,which include the orbital/triangle of the left middle frontal gyrus and the right inferior frontal gyrus,while wide areas of decreased gery density was found in severe COPD group including bilateral superior frontal gyrus,inferior frontal gyrus and orbital,superior temporal gyrus and parahippocampal gyrus,et al;and the atrophy in left brain is dominant.The correlation analysis showed that there was no significant correlation between gray matter density and blood oxygen index（Pao₂ and Sao₂）in COPD patients,while the gray matter density in left superior frontal gyrus and right inferior frontal gyrus was positively correlated with the total score of MOCA（r=0.233,P=0.048;r=0.293,P=0.009,respectively）and FEV1（r=0.433,P<0.001;r=0.659,P<0.001,respectively）.（3）Research 3:There were great differences in extensive areas of white matter（MD,AD and RD indices）among the four groups,including the genu,body and splenium of corpus callosum,bilateral cingulum（cingulate gyrus）,fornix,bilateral radiation corona,bilateral posterior thalamus radiation,bilateral internal capsule,left lateral capsule,left superior,inferior longitudinal tract and left inferior fronto-occipital tract.Compared with the control group,no significant statistical significant change of white matter was found in mild COPD patients.The change of white matter in moderate COPD patients was relatively limited,while the change of white matter in severe COPD patients was more extensive.With the increase of severity,there is an increase tendency of the impairment of white matter.No significant correlation was found between the intergrity of white matter and blood oxygen level,while the intergrity of the corpus callosum and bilateral coronal white matter was correlated with MOCA score and FEV1.Conclusion（1）COPD patients have cognitive impairment,which is correlated with pulmonary function and hypoxia,suggesting that hypoxemia and impairment of pulmonary function may be one of the risk factors of cognitive impairment in COPD patients.（2）In patients with COPD,the gray matter density of multiple brain regions in the prefrontal and limbic systems was decreased.The atrophy of gray matter gradually increased with the increase of the severity of the disease.The GM density in some areas such as left superior frontal gyrus and right orbital part of the inferior frontal gyrus is correlated with cognitive function and disease severity（FEV1）.It is suggested that the decline of pulmonary function in COPD patients may cause local gray matter atrophy leading to cognitive impairment.（3）There were extensive impairment in white matter in COPD patients.The impairment of white matter gradually increased with the increase of the disease severity.The intergrity of the white matter in bilateral upper radiation corona and body of corpus callosum is correlated with cognitive function and disease severity（FEV1）.It is suggested that the decline of lung function in COPD patients may cause local white matter damage leading to cognitive impairment.