Study On The Relationship Between Metabolic Syndrome And Subcortical Ischemic Vascular Cognitive Impairment

Part Ⅰ.The relationship between metabolic syndrome components and cognitive function of subcortical ischemic vascular cognitive impairmentBackground:Subcortical ischemic vascular cognitive impairment(SIVCI)which is the most common subtype of vascular cognitive impairment,is caused by subcortical cerebral infarction and white matter lesions.The patient can be diagnosed as metabolic syndrome(MetS)by experiencing three of the following components:abdominal obesity,hypertension,hyperglycemia,low HDL and high TG.MetS itself and its components are risk factors for ischemic cerebrovascular disease and associated with increased risk of cognitive impairment,but there are few studies on the relationship between MetS components and cognitive function of SIVCI.Objective:To analyze the relationship between MetS components and cognitive function of SIVCI,and to compare the accuracy,sensitivity and specificity of MMSE and MoCA in assessing cognitive function in SIVCI patients.Methods:This cross-sectional study recruited 140 SIVCI patients suffering from MetS components.The patients were assigned to five groups according to the number of MetS components:group Ⅰ(n = 29;one MetS component),group Ⅱ(n = 28;two MetS components),group Ⅲ(n = 27;three MetS components),group Ⅳ(n = 28;four MetS components),and groupⅤ(n = 28;five MetS components).They were divided into non-MetS group(No-MetSgroup;the number of MetS components ≤2;n = 57)and MetS group(the number of MetS components ≥3;n = 83)according to the absence or presence of MetS.MetS was diagnosed in accordance with the NCEP-ATPIII criteria.All subjects filled in the clinical’material forms,had blood tests,underwent brain MRI and neuropsychological assessments.The differences in cognitive impairment were compared among groups Ⅰ-Ⅴ and between MetS and non-MetS groups.The linear-by-linear association test was used to analyze the trend of dementia incidence with the increased number of MetS components.The accuracy,specificity and sensitivity of MMSE and MoCA screening for dementia were analyzed by plotting the receiver operating characteristic curve and the area under the curve.Logistic regression analysis was performed on the potential risk factors for dementia in SIVCI patients.Results:1)There was no statistically significant difference in the sociological status of patients in each group(P>0.05).2)MMSE and MoCA gradually decreased with the increasing number of MetS components,but they did not achieve statistical significance(P>0.05).Among the seven items of MoCA,the other six items except ion were significantly different(P<0.05).However,further pairwise comparison revealed that not every difference between the two groups was statistically significant,so the differences between groupⅠ and groups Ⅲ,Ⅳ and Ⅴ,and between group Ⅱ and groups Ⅲ,Ⅳ and Ⅴ were compared.Between group Ⅰ and groups Ⅲ,Ⅳ and Ⅴ,MMSE and MoCA were significantly different(P<0.05).Between group Ⅱ and groupsⅢ,Ⅳ andⅤ,MMSE was significantly different(P<0.05).Between group Ⅱ and groupsⅣ and Ⅴ,MoCA was significantly different(P<0.05).MMSE and MoCA scores were significantly lower in the MetS group than in the No-MetS group(P<0.05).Among the seven items of MoCA,five items except attention and ion were significantly different between the MetS and No-MetS groups(P<0.05).3)With the increased number of MetS components,the risk of dementia was increased in SIVCI patients(Ptrend<0.0001).4)The area under the curve of MMSE and MoCA screening for dementia was 0.667 and 0.738,respectively.During screening for dementia,the critical values of MMSE and MoCA and their sensitivity and specificity were 22.5(66%/57.5%)and 18.5(75.5%/69%),respectively.5)The binary logistic regression analysis was performed with dementia as dependent variable and abdominal obesity,hypertension,hyperglycemia,low HDL,high TG,age,sex,years of education,smoking,drinking and heart disease as independent variables.Results demonstrated that subcortical vascular dementia may associate with abdominal obesity(B=2.489,OR=12.050,P=0.001),hypertension(B=2.264,OR=9.623,P<0.0001)and years of education(B=-0.209,OR=0.811,P=0.005).Conclusions:1)Cognitive function of SIVCI gradually decreased with the increased number of MetS components.The cognitive function of SIVCI patients with MetS was worse than that of SIVCI patients without MetS.The cognitive impairment was mainly based on visuospatial abilities and executive function,naming,language,delayed recall and orientation.2)The risk of dementia in SIVCI patients increased with the increased number of MetS components.3)MoCA had a high accuracy in assessing SIVCI.In the screening of dementia,the critical value of MoCA was lower than that of MMSE,and its sensitivity and specificity were higher than MMSE.4)Abdominal obesity and hypertension raise the risk of subcortical vascular dementia.The longer the SIVCI patients get education,the lower risk of subcortical vascular dementia was.Part Ⅱ.The relationship between metabolic syndrome components and structural imaging of subcortical ischemic vascular cognitive impairmentBackgrouncd:Anatomical basis of subcortical ischemic vascular cognitive impairment(SIVCI)is multiple lacunar infarctions(LI)and ischemic white matter lesion(WML).Metabolic syndrome(MetS)is a group of clinical syndromes with vascular risk factors,can damage small blood vessels,leading to LI and WML,and causing vascular cognitive impairment.At present,there are few studies on the relationship of MetS components with LI and WML,and it is full of controversy.Objective:To analyze the relationship between MetS components and structural imaging of SIVCI,and to compare the consistency of Scheltens scale and Fazekas scale in assessing the WML of SIVCI.Methods:This cross-sectional study recruited 140 SIVCI patients suffering from MetS components.The patients were assigned to five groups according to the number of MetS components:group I(n = 29;one MetS component),group II(n = 28;two MetS components),group III(n = 27;three MetS components),group IV(n = 28;four MetS components),and group V(n = 28;five MetS components).They were divided into non-MtS group(No-MetS group;the number of MetS components ≤2;n = 57)and MetS group(the number of MetS components ≥3 n = 83)according to the absence or presence of MetS.MetS was diagnosed in accordance with the NCEP-ATPIII criteria.All subjects underwent brain MRI,were assessed the number of LI,completed the scores of Scheltens and Fazekas.The number of LI foci and WML score were compared among the groups I-V,and between the MetS and No-MetS groups.The correlation between Scheltens and Fazekas scales was assessed.Regression analysis was used to analyze the factors affecting the total number of LI,the total score of Scheltens scale and the total score of Fazekas scale in SIVCI patients.Results:1)The number of LI in the basal ganglia and the subcortical white matter and total number of LI were significantly different among groups Ⅰ-Ⅴ(P<0.05).However,further pairwise comparison revealed that not every difference between the two groups was statistically significant,so the total number of LI gradually increased with the increasing number of MetS components,but it did not achieve statistical significance(P>0.05).Between group Ⅰ and groups Ⅳ and Ⅴ,the number of LI in the subcortical white matter and total number of LI were significantly different(P<0.05).The number of LI in the basal ganglia was significantly different between the group Ⅰ and group Ⅴ(P<0.05).Furthermore,the number of LI in the subcortical white matter and total number of LI were significantly different between the group Ⅱ and group Ⅴ(P<0.05).The number of LI in the basal ganglia and subcortical white matter and total number of LI were significantly different between the MetS and No-MetS groups(P<0.05).2)WML scores in the periventricular tissue and brain lobe and total score of Scheltens scale,WML scores in the periventricular tissue and deep white matter and total score of Fazekas scale were significantly different among the groups Ⅰ-Ⅴ(P<0.05).However,further pairwise comparison demonstrated that not every difference between the two groups was statistically significant,so the differences between group Ⅰ and groupsⅣ and Ⅴ,and between group Ⅱ and groups Ⅳ and Ⅴ were compared.Between group Ⅰ and groups Ⅳ and Ⅴ,WML scores in the periventricular tissue and white matter of the brain lobe and total score of Scheltens scale,WML scores in the periventricular tissue and total score of Fazekas scale were significantly different(P<0.05).Between group II and groups IV and V,WML score in the periventricular tissue and white matter of brain lobe and total score of Scheletens scale,and WML score in the deep white matter and total score of Fazekas scale were significantly different(P<0.05).The total score of Scheletens scale and total score of Fazekas scale gradually increased with the increasing number of MetS components,but they did not achieve statistical significance(P>0.05).WML score in the periventricular tissue,white matter of brain lobe,and total score of Scheletens scale,and WML score in the periventricular tissue and deep white matter and total score of Fazekas scale were significantly different between the MetS and No-MetS groups(P<0.05).3)Total score of Scheltens scale was positively correlated with total score of Fazekas scale(r=0.668,P<0.0001).4)With the increased total number of LI,total score of Scheltens scale and total score of Fazekas scale,the risk of dementia was increased in SIVCI patients(PLI总数 trend=0.008,P Scheltens trend<0.0001,PFazekas trend=0.001).5)Multivariate stepwise regression analysis was conducted with the total number of LI,total score of Scheltens scale and total score of Fazekas scale as dependent variables,abdominal obesity,hypertension,hyperglycemia,low HDL and high TG as independent variables.Results revealed that when the dependent variable was the total number of LI,the factors influencing the total number of LI were hyperglycemia(PO=0.290,P<0.0001),high TG(β =0.288,P=0.016)and abdominal obesity(β =0.264,P=0.020)according to their effect on the total number of LI(from big effect to small effect).Whern the dependent variable was the total score of Scheltens,the factors influencing the total score of Scheltens were low HDL-C(β=0.437,P<0.0001),hyperglycemia(β=0.255,P<0.0001),hypertension(β= 0.225,P<0.0001)and high TG(β=0.180,P=0.003)according to their effect on the total score of Scheltens(from big effect to small effect).When the dependent variable was the total score of Fazekas scale,the factors affecting the total score of Fazekas scale were low HDL-C(β＝0.328,P<0.0001),hypertension(β= 0.188,P=0.017)and abdominal obesity(β=0.159,P=0.041).Conclusions:1)The total number of LI and severity of WML in each brain area of SIVCI patients increased with the increased number of MetS components.Compared with SIVCI patients without MetS,the brain structural damage of SIVCI patients with MetS was severe.The risk of dementia in SIVCI patients increased with the increased severity of WML.2)Scheltens and Fazekas scales had a good consistency in assessing WML in SIVCI patients.3)MetS and its components aggravate structural brain damage.The factors leading to the increased total number of LI in SIVCI patients were hyperglycemia,high TG and abdominal obesity according to their effect on the total number of LI(from big effect to small effect).The factors leading to the increased the total score of Scheltens in SIVCI patients were low HDL-C,hyperglycemia,hypertension and high TG according to their effect on the total score of Scheltens(from big effect to small effect).The factors leading to the increased the total score of Fazekas scale in SIVCI patients were low HDL-C,hypertension and abdominal obesity according to their effect on the total score of Fazekas(from big effect to small effect).Part Ⅲ.Effect of metabolic syndrome components on carotid atherosclerosis and LOXL2 of subcortical ischemic vascular cognitive impairmentBackground:The common cause of ischemic cerebrovascular disease that induces SIVCI is atherosclerosis.The pathogenesis of atherosclerosis is endothelial dysfunction.LOXL2 is expressed in the endothelial cells and affects vascular endothelial function by extracelluar matrix construction and inflammatory reaction involved in ahteosclerosis.Carotid atherosclerosis is one of independent risk factors of atherosclerosis.Each component of metabolic syndrome(MetS)is a risk factor for atherosclerosis.However,effect of MetS on the CAS and LOXL2 of subcortical ischemic vascular cognitive impairment(SIVCI)is not clear.Objective:To analyze the effect of MetS components on CAS and plasma LOXL2 levels of SIVCI patients.To explore the relationship between plasma LOXL2 levels and carotid arterial IMT of SIVCI patients.Methods:This cross-sectional study recruited 140 SIVCI patients suffering from MetS components.The patients were assigned to five groups according to the number of MetS components:group Ⅰ(n = 29;one MetS component),group Ⅱ(n = 28;two MetS components),group Ⅲ(n = 27;three MetS components),group IV(n = 28;four MetS components),and group V(n = 28;five MetS components).They were divided into non-MetS group(nMetS group;the number of MetS components ≤2;n=57)and MetS group(the number of MetS components ≥3;n = 83)according to the absence or presence of MetS.MetS was diagnosed in accordance with the NCEP-ATPIII criteria.They were divided into hypertension group(n = 91)and No-hypertension group(n = 49)according to the presence or absence of hypertension.ELISA was performed to determine the levels of LOXL2 of subjects.Color Doppler ultrasound diagnosis of carotid arterial IMT,the character of plaque and the extent of carotid artery stenosis.The results were compared between groups.The differences in CAS and LOXL2 were compared among groups Ⅰ-Ⅴ and between MetS and non-MetS groups.The differences in LOXL2 were between hypertension group and No-hypertension group.The correlation between CAS and IMT was assessed.The linear-by-linear association test was used to analyze the trend of dementia incidence with the increased IMT.Logistic regression analysis was performed on the occurrence of moderate or above carotid stenosis and the formation of unstable plaque in SIVCI patients.Regression analysis was used to analyze the factors affecting IMT in SIVCI patients.Results:1)There was no statistically significant difference in the constituent ratio of the plaque properties of each group(P>0.05).2)The constituent ratio of carotid stenosis was significantly different among groups Ⅰ-Ⅴ(P<0.05).With the increase of the number of MetS components,the detection rate of severe carotid stenosis showed an increasing trend,but it was not statistically significant(P>0.05).The comparison between group Ⅰ and groups Ⅲ,Ⅳ and Ⅴ,and between groupⅡ and groups Ⅲ,Ⅳ and Ⅴ showed significant differences in the detection rate of severe carotid stenosis between group Ⅰ and groups Ⅲ,Ⅳ andⅤ,between group Ⅱ and groups Ⅳ and Ⅴ(P<0.05).There was no statistically significant difference in the incidence of moderate or above carotid stenosis of each group(P>0.05).Compared with the No-MetS group,the incidence of moderate and severe stenosis was increased in the MetS group(P<0.05).3)With the increase of the number of MetS components,the IMT showed an increasing trend,but it was not statistically significant(P>0.05).The comparison between group Ⅰ and groups Ⅲ,Ⅳ and Ⅴ,and between group II and groups III,IV and V showed significant differences in the IMT between group I and groups III,IV and V,between group II and groups IV and V(P<0.05).IMT was higher in the MetS group than in the No-MetS group(P<0.05).4)With the increase of the number of MetS components,the LOXL2 showed an increasing trend,but it was not statistically significant(P>0.05).The comparison between group I and groups III,IV and V,and between group II and groups III,IV and V showed significant differences in the LOXL2 between group I and groups III,IV and V,between group II and groups IV and V(P<0.05).LOXL2 was higher in the MetS group than in the No-MetS group(P<0.05).LOXL2 was higher in the hypertension group than in the No-hypertension group(P<0.05).5)LOXL2 level was positively correlated with IMT(r=0.461,P<0.0001).6)Trend analysis showed that with the increase of CCA-IMT,the risk of dementia in SVCI patients increased(Ptrend= 0.003).7)Multivariate stepwise regression analysis was conducted with IMT as dependent variables,and abdominal obesity,hypertension,hyperglycemia,low HDL and high TG as independent variables.Results revealed that when the dependent variable was IMT,the factors influencing IMT were hyperglycemia(β= 0.266,P= 0.001),low HDL(β= 0.236,P=0.003)and hypertension(β=0.215,P= 0.006)according to their effect on IMT(from big effect to small effect).The presence and absence of moderate or above carotid stenosis were used as dependent variable;and abdominal obesity,hypertension,hyperglycemia,low HDL-C,and hypertriglyceridemia were used as independent variables for binary logistic regression analysis.Results demonstrated that the occurrence of moderate or above carotid stenosis was possibly associated with hypertension(B=1.236,OR=3.442,P=0.003)and low HDL-C(B=1.336,OR=3.802,P=0.002).The presence and absence of unstable plaques were used as dependent variable;and abdominal obesity,hypertension,hyperglycemia,low HDL-C,and hypertriglyceridemia were used as independent variables for binary logistic regression analysis.Results demonstrated that the formation of unstable plaque in SVCI patients was probably associated with hyperglycemia(B=0.840,OR=2.315,P=0.042).Conclusions:1)MetS has no effect on the incidence of unstable carotid plaques in SVCI patients.With the increase of the number of MetS components,the detection rate of severe carotid stenosis and IMT showed an increasing trend.The incidence of moderate and severe stenosis and IMT were higher in the MetS group than in the No-MetS group.2)With the increase of the number of MetS components,the LOXL2 level showed an increasing trend.LOXL2 was higher in the MetS group than in the No-MetS group.LOXL2 was higher in the hypertension group than in the No-hypertension group.LOXL2 level was positively correlated with IMT.3)With the increase of CCA-IMT,the risk of dementia in SVCI patients increased.4)Among the five components of MetS,hyperglycemia was the most important factor leading to the increased IMT,followed by low HDL and hypertension,hypertension and low HDL-C are influencing factors for the occurrence of moderate or severe carotid stenosis in SVCI patients,hyperglycemia is the influencing factors for the formation of unstable plaque in SIVCI patients.Part Ⅳ The relationship between metabolic syndrome components andplasma adipocytokines levels of subcortical ischemic vascular cognitive impairmentBackground:Inflammation,endothelial dysfunction,and thrombosis may be involved in the pathogenesis of vascular cognitive impairment(VCI).Adipokines secreted by adipose tissue participate in the regulation of inflammation and atherosclerosis,play an important role in the pathogenesis of metabolic syndrome(MetS),and may participate in the pathological process of vascular cognitive impairment.Tumor necrosis factor-α(TNF-α),plasminogen activator inhibitor-1(PAI-1)and adiponectin(APN)released by lipocytes all participate in the regulation of inflammation and energy metabolism,regulate atherosclerosis and may have the relationship with the occurrence and development of vascular cognitive impairment.Objective:To analyze the relationship between MetS components and plasma adipocytokines levels of subcortical ischemic vascular cognitive impairment(SIVCI).To explore the relationship between plasma adipocytokines and structural brain damage,carotid atherosclerosis,cognitive function of SIVCI patients.Methods:This cross-sectional study recruited 140 SIVCI patients suffering from MetS components.The patients were assigned to five groups according to the number of MetS components:group I(n = 29;one MetS component),group II(n = 28;two MetS components),group III(n = 27;three MetS components),group IV(n = 28;four MetS components),and group V(n = 28;five MetS components).They were divided into non-MetS group(nMetS group;the number of MetS components<2;n = 57)and MetS group(the number of MetS components≥3;n = 83)according to the absence or presence of MetS.MetS was diagnosed in accordance with the NCEP-ATPIII criteria.ELISA was performed to determine the levels of APN,TNF-α and PAI-1.The differences in the levels of APN,TNF-α and PAI-1 were compared among groups I-V and between MetS and non-MetS groups.The correlation between plasma adipocytokines and structural brain damage,carotid atherosclerosis,cognitive function was assessed.The linear-by-linear association test was used to analyze the trend of dementia incidence with the increased plasma adipocytokines levels.Regression analysis was used to analyze the factors affecting APN,TNF-α and PAI-1 in SIVCI patients.Results:1)The levels of APN,TNF-a and PAI-1 were significantly different among groups Ⅰ-Ⅴ(P<0.05).However,further pairwise comparison revealed that not every difference between the two groups was statistically significant,so the differences between group Ⅰ and groups Ⅲ,Ⅳ and Ⅴ,and between group Ⅱ and groups Ⅲ,IV and V were compared.Between group I and groupsⅢ,Ⅳ and V,levels of APN,TNF-α and PAI-1 were significantly different(P<0.05).Between group Ⅱ and groups Ⅲ,Ⅳ and Ⅴ,levels of APN,TNF-a and PAI-1 were significantly different.The levels of APN,TNF-a and PAI-1 were significantly different between MetS and No-MetS groups(P<0.05).2)PAI-1 level was significantly negatively correlated with APN level(r=-O.617,P<0.001).PAI-1 was significantly positively correlated with TNF-α(r=0.733,P<0.0001).TNF-a was significantly negatively correlated with APN(r=-0.602,P<0.0001).3)With the increased level of TNF-a and PAI-1,the risk of dementia was increased in SIVCI patients(PTNF-αtrend<0.0001,PPAI-1trend=0.001).With the increased level of APN,the risk of dementia was decreased in SIVCI patients(Ptrend =0.001).4)APN level was negatively correlated with the total number of LI(r=-0.416,P<0.0001),the total score of Scheltens(r=-0.565,P<0.0001),the total score of Fazekas(r=-0.303,P=0.003)and IMT(r=-0.361,P<0.0001).APN level was positively correlated with MoCA(r=0.562,P<0.0001).TNF-α level was positively correlated with the total number of LI(r=0.498,P<0.0001),the total score of Scheltens(r=0.704,P<0.001),the total score of Fazekas(r=0.418,P<0.0001)and IMT(r=0.483,P<0.0001).TNF-a level was negatively correlated with MoCA(r=-0.587,P<0.0001).PAI-1 level was positively correlated with the total number of LI(r=0.459,P<0.0001),the total score of Scheltens(r=0.632,P<0.0001),the total score of Fazekas(r=0.355,P<0.0001)and IMT(r=0.474,P<0.0001).PAI-1 level was negatively correlated with MoCA(r=-0.605,P<0.0001).5)Multivariate stepwise regression analysis was conducted with APN,TNF-α and PAI-1 as dependent variables,and abdominal obesity,hypearglycemia,hypertension,low HDL-C and high TG as independent variables.Results revealed that when the dependent variable was APN,the factors influencing APN were hyperglycemia(β=-0.462,P<0.0001),low HDL-C(β=-0.257,P<0.0001),high TG(β=-0.228,P<0.0001)and hypertension(β=-0.031,P=0.033)according to their effect on APN(from big effect to small effect).When the dependent variable was TNF-α the factors influencing TNF-a were abdominal obesity(0 =0.335,P<0.0001),hyperglycemia(β=0.333,P<0.0001),high TG(β=0.295,P<0.0001),hypertension(β=0.273,P<0.0001)and low HDL-C(β=0.261,P<0.0001)according to their effect on TNF-α(from big effect to small effect).When the dependent variable was PAI-1,the factors influencing PAI-1 were hyperglycemia(β=0.373,P<0.0001),highTG(β=0.368,P<0.0001),low HDL-C(β =0.208,P<0.0001),hypertension(β=0.196,P<0.0001)and abdominal obesity(β=0.191,P<0.0001)according to their effect on PAI-1(from big effect to small effect).Conclusions:1)With the increased number of MetS components,plasma APN levels gradually decrease,and plasma TNF-α and PAI-1 levels gradually increase in SIVCI patients.Compared with SIVCI patients without MetS,plasma APN levels were diminished,and plasma TNF-a and PAI-1 levels were increased in SIVCI patients with MetS.2)PAI-1 and TNF-αmay be contributing factors for SIVCI.APN may be one of the protective factors for SIVCI.3)MetS and its components are the effect factors of carotid atherosclerosis.The influencing factors of APN were hyperglycemia,low HDL-C,high TG and hypertension according to their effect on APN(from big effect to small effect).The influencing factors of TNF-α were abdominal obesity,hyperglycemia,high TG,hypertension and low HDL-C according to their effect on TNF-α(from big effect to small effect).The influencing factors of PAI-1 were hyperglycemia,high TG,low HDL-C,hypertension and abdominal obesity according to their effect on PAI-1(from big effect to small effect).