| As people's lifes are gradually extended,more and more patients are sufferring from cognitive impairment.The most common neurodegenerative dementia is senile dementia such as Alzheimer's disease and vascular dementia.Since the control of vascular risk factors and mild vascular cognitive impairment can effectively prevent vascular dementia,the study of mild vascular cognitive impairment has attracted more attention currently.At present,the prevention of cerebrovascular disease has mainly focus on macrovascular disease and cardiogenic embolism while cerebral small vessel disease has been usually ignored which causes 50%of vascular dementias.Cerebral small vessel disease mainly includes lacunar cerebral infarction,leukoaraiosis,and cerebral microbleeds.It rarely causes focal nervous system dysfunction.Therefore,less attention is taken into cerebral small vessel disease.In the early stage,the cogntitive impairment caused by cerebral small vessel disease is difficult to be found and diagnosed resulting in poor post-treatment and severely affecting the patient's life quality and bringing a heavy burden on families and society.Vascular cognitive imPairment(VCI)is a series of diseases including mild cognitive imPairment without dementia and vascular dementia(VaD).It is the second cause of senile dementia in China.Currently,VCI is the only dementia disease that can be Prevented because of its early reversibility.As a result,it is imPortant to identify Patients at early stage of cognitive imPairment and to treat aPProPriately.However,the diagnosis and classification of VCI at Present is still based on clinical manifestations and neuroPsychological scales which are subjective and not conducive to early clinical diagnosis and Prevention.Cerebral microbleeds(CNBs),which has been considered as a significant risk factor for cognitive imPairment in Patients with VCI,is difficult to be identified by routine examination such as CT and MRI.SuscePtibility weighted imaging(SWI)utilizes the difference in magnetic sensitivity between tissues to generate image contrast and obtain amPlitude images and Phase images.Therefore,SWI can be aPPlied to detect Paramagnetic substances such as iron and hemorrhage Products(deoxyhemoglobin,methemoglobin and so on)with relatively high detection rate and can show the hemorrhage very sensitively.On the other hand,although a correlation between the degree of cognitive imPairment and white matter damage has been observed in VCI Patients,conventional magnetic resonance imaging cannot reflect the changes in the microstructure of white matter fiber.Diffusion tensor imaging(DTI)uses the diffusion anisotroPy of water molecules to detect the function of water molecule exchange among various components in the Pathological state of living tissue.DTI can sensitively reflect the structure of white matter fibers in the brain.Consequently,SWI and DTI detection are of great importance for the early diagnosis and early treatment of VCI Patients.Finally,the mechanism of VCI may involve immune and inflammatory resPonses,in which the inflammatory resPonse Plays an imPortant role in demyelinating lesions of the white matter characterized by aPoPtosis of oligodendrocytes and loss of myelin Proteins.There may be some correlation between cognitive impairment and the changes of some inflammatory factors in cerebrosPinal fluid or blood.Therefore,detecting the level of related inflammatory markers and further understanding its role in cognitive impairment can contribute to the early Prevention and treatment of VCI Patients.In this study we aPPlied SWI,DTI and serum inflammatory marker detection in VCI Patients,combined with neuroPsychological testing,to estimate neuroPsychological Profile and white matter characteristics in Patients with cerebral vascular disease.The clinical and auxiliary examination characteristics of Patients with VCI were grasPed and the risk factors as well as the mechanisms of small cerebral vascular diseases are elucidated in order for finding imaging markers and inflammatory markers with high and specific sensitivity.This work will Provide some new ideas and methods for clinical Prevention,diagnosis and treatment in VCI Patients.Part 1:The study of correlation between vascular cognitive impairment and cerebral microbleeds detected by suscePtibility weighted imagingObjectives:To investigate the correlation between the quantities and locations of cerebral microbleeds(CMBs)and the cognitive function and to exPlore the relationship between structural microscoPic features of microbleeds and cognitive impairment.To search for related risk factors and imaging markers of CMBs and to Provide theoretical reference for early clinical Prevention,diagnosis and treatment in Patients with VCI.Methods:Patients with cerebral vascular disease diagnosed by MRI and SWI in the Department of Neurology in our hosPital from June 2016 to June 2017 were selected.The basic information of these Patients,such as age,gender,systolic and diastolic Pressure,fasting blood glucose,total triglycerides,total cholesterol,high-density liPoProtein,low-density liPoProtein,homocysteine,C-reactive Protein,tumor necrosis factor-a,interleukin-6,etc.,were collected.The Past medical history,such as coronary heart disease,hyPertension,and history of diabetes,were asked in detail.A further head SWI scan was Performed on eligible individuals.According to the Presence or absence of CMBs,the Patients are divided in two grouPs:cerebral microbleeds Positive grouP and cerebral microbleeds negative grouP.The number of Pateints with cerebral microbleeds,the quantity and location of cerebral microbleeds in each case were recorded while the number of lacunar infarctions and the degree of leukoaraiosis were recorded,respectively.Global cognitive status was assessed with the Mini-Mental Status Examination(MMSE)and montreal cognitive assessment(Mo CA).According to the result,Patients with cognitive impairment were divided into those with VCI and no dementia(VCIND)and vascular dementia(VaD).The control grouP with normal cognitive function was selected from healthy volunteers.All of them were subjected to cerebral MRI and SWI examination and relevant clinical data were recorded.Results:(1)The risk of CMBs increased in older Patients;the Possibility of CMBs in Patients with a history of hyPertension,Prior antiPlatelet aggregation,and leukoaraiosis is higher than in those without these diseases;CMBs occur in men more often than women;(2)ComPared to the VCIND grouP,the number of microbleeds increased significantly in Patients of the VaD grouP,while only few microbleeds were detected in control grouP;The microbleeds mainly located in the lobes:frontal lobe,temPoral lobe cortex,basal ganglia,semiovale center,radiograPhy canoPy,and thalamus and the subocciPal cerebral microbleeds was rare;The number of CMBs was negatively correlated with cognitive function as the degree of cognitive impairment became severe when the number of CMBS rose;(3)CMBs were significantly associated with the scores in MMSE and MOCA tests.ComParing Patients with CIND and VaD with the control ones,there were statistically significant differences in the scores by MMSE and Mo CA tests as well as the executive functions(P<0.05).Patients with VCIND has significant significance in abstract ability scores while the VaD grouP has statistical significance in memory scores comPared with the control grouP(P<0.05);(4)There was a negative correlation between the number of CMBs and the total scores of Mo CA(r=-0.814,P=0.001);in Particular,there was a negative correlation between exercise(r=-0.520,P=0.003)and memory(r=-0.431,P=0.042)abilities.There is no obvious correlation between CMBs and attention,naming,language,calculation,abstraction ability and orientation;(5)The risk of cognitive impairment was increased in the VCIND grouP excePt for the subconjunctival(cerebellum,brainstem)and basal ganglia hemorrhage,especially in the frontal lobe,with a statistically significant difference;in the VaD grouP,the risk of cognitive impairment increased excePt for basal ganglia and cerebellar microbleeds,and the relationship with the bleeding in the frontal lobe was more significant,with statistical significance;(6)There was a negative correlation between frontal CMBs and executive function(r=-0.321,P=0.025),abstraction ability(r=-0.274,P=0.032);there was a negative correlation between CMBs in temPoral lobe and executive function(r=-0.247,P=0.031),and memory(r=-0.235,P=0.034);CMBs in basal ganglia were associated with MMSE,MoCA,and attention(r=-0.236,P=0.031),(r=-0.247,P=0.023),(r=-0.357,P=0.019);CMBs in thalamus was associated with attention(r=-0.245P=0.033)and orientation(r=-0.268,P=0.031);however,CMBs in the subcolumn did not show correlation with each grouP.Conclusions:(1)Comprehensive assessment of the number and location of CMBs Plays an imPortant role in assessing cognitive impairment;(2)SWI reflect that the degree and the number of CMBs has a strong correlation with the degree of cognitive impairment.As a result,SWI results can be used as one of the imaging markers of the degree of cognitive impairment caused by cerebral microbleeds to Predict the occurrence of cognitive impairments and suggest the development of vascular cognitive impairment.Part 2:Investigation of white matter microstructural lesions in leukoaraiosis Patients with vascular cognition impairment by diffusion tensor imagingObjective:To comPare the degree of microstructural white matter lesions(WML)in VCIND Patients and VaD Patients and to establish a correlation between microstructural white matter lesions and cognition impairment by diffusion tensor imaging(DTI)as the main research method,combined with neuroPsychological testing.To systematic analyze of the relationship between the location of white matter lesions and cognitive function in Patients with leukoaraiosis,and to seek imaging markers of vascular cognitive impairment caused by leukoaraiosis for early detection,early Prevention,and early treatment in VCI Patients.Methods:According to the MRI diagnostic criteria,60 LA Patients were envolved,and 30 healthy Patients with comParable age were selected as normal control grouP.According to the diagnostic criteria of cognitive imPairment,LA Patients were divided into VaD grouP(30 cases)and VCIND grouP(30 cases).Subjects' age,gender and education level were recorded and neuroPsychology MMSE and Mo CA tests,including multiple cognitive factors such as memory,attention,language,visual sPatial structure and executive function,etc.,were Performed by well trained Professional doctors.MRI and DTI examinations were acquired and the WML were classified according to the age-related white matter grading method.The correlation analysis was used to exPlore the relationship between cognitive function and WML.The fraction anisotroPy(FA)and aPParent diffusion coefficient(ADC)of the white matter(including the lesion and the normal Part)of the bilateral frontal lobe,temPoral lobe,occiPital lobe,centrum semiovale,lateral ventricle,and thalamus were measured,respectively.Differences in DTI Parameters between the three grouPs were analyzed and correlation analysis was Performed for the results of neuroPsychological tests in multiple cognitive domain in VCIND grouP.Results:(1)The neuroPsychological scores and white matter lesion scores of the three grouPs were comPared and there was a statistically significant difference between the grouPs(P<0.05).ComPared with the normal control grouP,the VaD grouP showed significantly lower MMSE and Mo CA scores and higher WML scores with significant difference in statistics(P<0.01);comPared with the normal control grouP,VCIND grouP exhibited lower MMSE and Mo CA scores and higher WML scores with statistical difference(P<0.05).ComParing VaD grouP and VCIND grouP,the former showed increasing MMSE and Mo CA scores and the difference was statistically significant(P<0.05).There was no statistical difference in the white matter scores between VCIND and VaD grouPs(P>0.05).(2)As the degree of cognitive imPairment aggravated,the scores and grades of white matter lesions in all sites increased accordingly.ExcePt the temPoral lobe,the scores of white matter lesions in all other sites were statistically significant(P<0.05).(3)The FA value and ADC values of each brain region of the three grouPs were comParable,with statistical difference(P<0.05).ComPared with the normal control grouP,the FA values of-each interest area of VaD Patients were significantly decreased and ADC value increased(P<0.05).In the VCIND grouP,the FA values decreased and ADC values increased(P<0.05).There were statistically significant differences between the VaD grouP and the VCIND grouP(P<0.05).(4)Controlling the age and level of education and eliminating the influence of WML and VaD,the correlation analysis for all subjects in VCIND grouP showed that the DTI indicators associated with cognitive function include:the FA values of the bilateral centrum semiovale,temPoral lobe and lateral ventricle were Positively correlated with MMSE and Mo CA scores;the ADC values of the bilateral centrum semiovale,the temPoral lobe,and the lateral ventricle were negatively correlated with the MMSE and Mo CA scores(P<0.05).The FA values of bilateral frontal lobe,temPoral lobe,occiPital lobe,centrum semiovale,lateral ventricle and thalamus were Positively correlated with the scores of executive function.The ADC values of bilateral frontal lobes,occiPital lobes,centrum semiovale,lateral ventricle and thalamus were negatively correlated with the score of executive function(P<0.05).The FA values of bilateral temPoral lobe were Positively correlated with the score of nomenclature function while the ADC values of bilateral temPoral lobe were negatively correlated with the score of nomenclature function(P<0.05).The FA values of bilateral temPoral lobe and lateral ventricle were Positively correlated with the score of memory function while the ADC values of bilateral temPoral lobe is negatively correlated with the score of memory function(P<0.05).The FA values of bilateral temPoral lobe and lateral ventricle were Positively correlated with the score of attention function while the ADC values of bilateral frontal lobes,centrum semiovale and lateral ventricle were negatively correlated with the score of attention function(P<0.05).The FA values of the frontal lobe,lateral ventricle,centrum semiovale and thalamus were Positively correlated with the score of the abstract function while the ADC values of the frontal lobe,centrum semiovale and lateral ventricle was negatively correlated with the score of the abstract function(P<0.05).The FA and ADC values in each brain area were not correlated with language and orientation,suggesting that language function was rarely influenced in the early stage of cognitive impairment and there was no statistical significance(P>0.05).Conclusions:(1)As the degree of cognitive imPainnent increases,the scores in neuroPsychological tests gradually decrease,meanwhile the scores in white matter lesions gradually increase.The first grade white matter lesions usually occurred in Patients with mild cognitive impairment or in normal PeoPle,and about one-third of the normal PeoPle had white matter changes;Patients with white matter lesions of the second grade and higher level were suffered from cognitive impairment and more than 30%of them showed dementia Performance;Grade 3 white matter lesions are accomPanied by dementia with varying degrees.However,it was difficult to distinguish VCIND and VaD only dePending on the white matter scores,which was not favorable to early diagnosis for cognitive impairment.Part 3.Clinical significance of serum inflammatory markers in leukoaraiosis Patients with vascular cognitive impairmentObjective:To investigate the sensitivity c-reactive Protein(CRP),interleukin-6(IL-6)and Tumor necrosis factor-?(TNF-?)in the serum of Patients with LA.Level and its correlation with cognitive impairment and white matter lesions.Finding serum biomarkers of morbidity is exPected to bring hoPe to early clinical diagnosis.Methods:The above 90 subjects were tested by enzyme-linked immunosorbent assay(ELISA),and serum levels of CD40L,IL-6,and hs CRP in the subjects were measured and Processed in Parallel for further analysis about cognitive function and the relevance of white matter lesions.Results:(1)Serum CRP level:ComPared with the normal control grouP,the serum CRP level in the LA grouP was increased,and the difference was statistically significant(P<0.05).There was a statistically significant difference between VaD grouP and VCIND grouP(P<0.05).IL-6 levels;(2)Interleukin-6 levels:ComPared with the healthy control grouP,serum IL-6 levels in LA grouPs were increased,with statistical differences(P<0.05).There was no statistically significant difference between Va D grouP and VCIND grouP(P<0.05);(3)TNF-a level:CRP concentration in Va D grouP was higher than that in normal control-grouP,the difference was statistically significant(P<0.05).There was a statistically significant difference between the VCIND grouP and the control grouP(P<0.05).(4)Correlation analysis:The serum CPR,IL-6 and TNF-a levels in the case grouP were correlated with the MMSE,Mo CA scores,and WML correlation.The statistical results showed that the levels of the three inflammatory factors were related to MMSE.However,there was no significant statistical significance;there was a significant correlation between Mo CA scores(P<0.05);correlations between serum CPR,IL-6 and TNF-a concentrations and WML scores were analyzed in LA Patients,and the levels of three inflammatory factors were comParable.There was no significant correlation between WML scores(P>0.05).Conclusions:(1)Serum CPR,IL-6 and TNF-a levels in Patients with cognitive imPairment caused by LA are significantly higher than those in the normal elderly,and have a negative correlation with MOCA scores.Inflammatory factors may be involved in the occurrence of cognitive imPairment in LA.,develoPment Process;(2)serum CPR,IL-6 and TNF-a levels and white matter lesions damage was not significantly related.(3)Serum CPR,IL-6,and TNF-? levels cannot be used alone as serum biomarkers for cognitive imPairment in Patients with early vascular leukoaraiosis. |
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