The Risk Factors Of White Matter Lesions And The Interation With Cognition And Depression

Background:White matter lesions(WML)is one of the hallmarks of small vessel disease(SVD),and the other imaging feature of SVD is lacunar infarction(LI),which may be the most common subtype of vascular cognitive impairment(VCI).SVD is closely related with aging,hypertension,diabetes,hyperhomocysteinemia and other risk factors such as arterial stenosis and carotid atherosclerotic plaques.WML is also closely related with cognitive function.The effect of WML on cognition is samely related with aging and other brain structural changes in AD.It is unclear whether the relationship between WML and cognition is independent of other risk factors,including vascular risk factors,brain atrophy and arteriosclerosis.WML patients commonly accompanied with cortical,subcortical atrophy and ventricular enlargement,so researchers suggested that the cognitive dysfunction in WML patients be mainly due to brain atrophy.Does WML cause cognitive impairment to be independent of brain atrophy and structural changes in brain structure?SVD patients often have depression and cognitive impairment at the same time.Depression is a multifactorial mood disorder,cerebrovascular factors including brain atrophy and cerebrovascular disease(WML)are likely to be involved,which making the relationship between depression and cognitive impairment be more complex.The changes in brain structure involving mood regulation and cognitive function are concerned in the study of depressive symptoms and cognitive impairment.However,these factors such as vascular factors and brain atrophy are also involved in the process of cognitive impairment.What is the interaction between LLD and cognition and WML?How is the role of vascular risk factors in them?The early clinical manifestations of WML patients are hidden,heterogeneous.WML patients with mild cognitive impairment(MCI)with high mortality and developed rapidly,so we want to explore the early characteristics of SVD-MCI patients.To resolve the above questions,we explore through the following four aspects:Part ?:Analysis the risk factors of the Oldest-old with different degrees of white matter lesions.Objective To investigate the independent risk factors of the oldest-old with different degree cerebral white matter lesions(WML)and provide the evidence for forecasting the progression of WML.Methods Brain magnetic resonance images(MRI)from 157 old people aged from 74 to 93 were analyzed.The severity of WML was rated with the Fazekas scale and divided into non-WML(control)group,mild-WML(WML 1 level)group and moderate-severe WML(WML 2 level)group.Cognitive score,vascular risk factors,cerebral hemodynamic and arteriosclerotic index,and radiological features were compared among the groups.Subsequent one-way anoval and multivariate logistic analysis were performed to determine the statistical significance factors and the independent risk factors among groups.Results The statistical significance factors with one-way anoval analysis among the three groups were cognitive performance(F=48.595,P=0.000),hypertension(?2=7.052,P=0.029),cigarette history(?2=19.476,P=0.000),cholesterol(TC)(F=3.086,P=0.049),Crouse score(F=3.968,P=0.021)and multiple radiological index.When WML 1 level group compared with controls,cigarette history(OR 2.031,95%CI 1.244?1.317),lacunar infarction(LI)numbers(OR 2.031,95%CI 1.316?4.015)and cholesterol(OR 1.610,95%CI 0.972?2.668)(P<0.05)were independent risk factors.The independent risks factors between WML 2-1 groups were cognitive performance(OR0.276,95%C1 0.143?0.532),cigarette history(OR 2.262,95%CI 1.260?4.059),and sylvian fissure ratio(SFR)(OR 1.954,95%CI 1.013?3.768)(P<0.05).The independent risk factors between the WML2 level group and control group were cognitive performance(OR 0.091,95%CI 0.030?0.273),bicaudate ratio(BCR)(OR 2.511,95%CI1,147?5.499),Crouse score(OR 2.304,95%CI1.127?4.712)and LI numbers(OR 2.200,95%CI1.028?4.707)(P<0.05).Conclusions Mild-WML patients have no significant changes in cognition,brain atrophy and cerebral atherosclerosis.Moderate-severe WML patients manifest remarkable cognitive disorder and cerebral atherosclerosis and brain atrophy.Compared with the controls,cognitive performance,BCR,Crouse score,LI numbers were the independent risk factors of moderate-severe WML patients.Part?:The relationship of cognitive score and radiological features of the different degrees white matter lesions elderly patientsObjective Analysis the traits and relationship of cognitive score and radiological features of the elderly people with different degree cerebral white matter lesions(WML).Methods Brain magnetic resonance images(MRI)from 151 old people were analyzed.The severity of WML was rated with the Fazekas scale and divided into WML 0 level(62 cases),WML 1 level(46 cases)and WML 2 level(43 cases)groups.One-way anoval and multivariate logistic and linear regression analysis were performed to determine the difference and the independent risk factors among the groups and relationships between the risk factors of Montreal cognitive assessment(MoCA)score and radiological features.Results Compared with WML 0 level group,WML 1 level group have no significant difference in each MoCA score,however the cognitive impairment of WML 2 level group was involved multifields of MoCA score(P<0.01).After controlling the brain atrophy factors,WML grade was still significant correlated with cognitive score(r =-0.448,P=0.000).Compared with WML 0 level group,the widen ratio of the interuncal distance with the bitemporal distance and the bicaudate ratio and the increased numbers of lacunar infarction(LI)were the independent risk factors of WML 2 level group.Regression analysis imply executive function significant correlated with subcortical atrophy(P<0.01),temporal lobe atrophy and the increased numbers of LI(P<0.05).Conclusion Mild-WML patients have no significant difference in cognition and brain atrophy,while moderate-severe WML patients are associated with extensive cognitive impairment and brain atrophy which imply impaired executive function caused by wrecked frontal cortical and subcortical circuits was the character of moderate-severe WML patients.Part ?:Late life depression and cognition and white matter lesion:interaction with cerebrovascular factors.Objective To investigate the relationship among the late-life depression(LLD)and cognitive function and white matter damage(WML),after excluding vascular risk factor and brain atrophy.Methods Using a variety of neurological scales assess the depression and cognition state of 277 patients and divided them into late-life depression group(LLD)and the non-depressed group,applying independent samples t test and multivariate logistic regression analyzes independent risk factors for depressive symptoms,in the Model ? of controlling age,sex and years of education and the Model ? of controlling age,sex and years of education,high blood pressure,diabetes and coronary heart disease.Under the premise of control mode ? and brain atrophy,using partial correlation analyze the correlation of depressive symptoms and cognitive function and WML and the correlation between depressive symptoms and cognitive items.Results The results of independent samples t-test showed that the proportion of high blood pressure((?2?6.342,P?0.046)),cognitive scores(t=3.343,P?0.001),WML2 level proportion(?2?7.373,P= 0.025)and temporal lobe atrophy of hippocampal sulcus ratio(t?-2,041,P=0.044)has the significant difference between the two groups.Multivariate logistic regression showed cognitive function is an independent risk factor for depression.Controlling for all risk factors,partial correlation analysis showed depressive symptoms were significantly correlated with cognitive function(r?-0.239,P=0.004)and white matter lesions(r = 0.222,P= 0.008)and the atrophy of temporal lobe and hippocampus(r=0.173,=0.040).Depressive symptoms correlated with attention(r =-0.175,P = 0.040),memories(r =-0.140,P = 0.040),drawing clock test(r =-0.186,P =0.029).Conclusion:Excluding vascular risk and brain atrophy and WML,cognitive impairment has significant correlation with depressive symptoms.Vascular risk factors are involved in the occurrence of depression,and WML may be the severity of cognitive impairment reserve markers.LLD patients showed hippocampal atrophy similar with early AD,manifesting the cognitive feature of damaging in executive dysfunction and attention disorders and memories.Part ?:Identify the early risk factors of the AD and SVD etiological mild cognitive impairmentObjective Discussion the feature of the two different etiological mild cognitive impairment due to subcortical small vessel disease(MCI-SVD)and Alzheimer's disease(MCI-AD)in the aspects of vascular risk factors and arteriosclerosis and cerebral anatomy.Methods The clinical data of 48 cases of MCI-SVD patients,40 cases of MCI-AD patients and 59 elderly controls were collected.Using the Clinical Dementia Rating(CDR)and the Montreal Cognitive Assessment(MoCA)Chinese Version to assess cognitive function.After admission,we recorded the patients' left side(LCCA)and right side internal carotid artery(RCCA)intima-media thickness(IMT)and plaque score(Crouse score)and the last paragraph of the internal carotid artery(ICA),middle cerebral artery(MCA),anterior cerebral artery(ACA),posterior cerebral artery(PCA),vertebral artery(VB),basilar artery(BA)mean pulsatility index(MPI)by color Doppler ultrasound.At the same time,the brain anatomical data of the patients with MRI were collected with the linear measurement method.Results Compared with the control group,in MCI-AD group the ratio of hypertension,diabetes and smoking was significantly increased,and the score of MoCA and LDL-C,ApoB were significantly decreased(P<0.05?0.01);There was no significant difference of vascular risks between the MCI-AD group and the MCI-SVD group(all P>0.05).Compared with the control group,in MCI-AD group the scores of visuospatial and executive function,attention,calculation,abstract,delayed recall,clock drawing were significant lower(P<0.05?0.01),in MCI-SVD group the ability of visuospatial and executive function,attention,calculation,abstract,delayed recall,clock drawing significantly decreased(P<0.01).The scores of visual spatial and executive function in MCI-AD group were significantly higher than those in group MCI-SVD(P<0.05).Compared with the control group,the Crouse score and the MPI of BA were significantly higher in MCI-SVD group(all P<0.05).Compared with the control group,MCI-AD group have significantly increased in widest sulcus,hippocampal sulcus ratio(P<0.01)and MCI-SVD group increased in the third ventricle and the caudate nucleus index(P<0.01).In MCI-AD group the widest sulcus was significantly higher than that in MCI-SVD group(P<0.05).Conclusion Both MCI-AD and MCI-SVD patients showed damage in multiple areas of cognition.MCI-SVD patients showed more damage on executive function.MCI-AD patients manifest cortical and hippocampal atrophy which reflects memory related hippocampal medial temporal lobe function pathway damage.MCI-SVD patients showed subcortical atrophy,possibly through the frontal subcortical circuits damage caused cognitive dysfunction.Cortical atrophy was more significant in MCI-AD patients.