Impact of Cholinergic Pathway Damage on Cognitive Impairment Caused by Cerebral White Matter Lesions / 中国康复理论与实践

Objective To investigate the relationship between cholinergic pathway damage and the executive dysfunction of patients with different degrees of cognitive impairment caused by cerebral white matter lesions(WML). Methods From March,2016 to December,2017,115 patients were recruited,whose characteristics,such as age,gender, education,and history of hypertension,diabetes and stroke were recorded.According to the T2-weighted MRI,80 patients were defined as WML.WML patients were divided into cognitively normal(CN)group(n=41),vascular cognitive impairment of none dementia(VCIND)group(n=21)and vascular dementia(VaD)group(n=18)ac-cording to the result of Montreal Cognitive Assessment(MoCA)and Clinical Dementia Rating(CDR).Other 35 cases without WML and cognitive impairment were as control group.WML under MRI were evaluated with Cho-linergic Pathways Hyperintensities Scale(CHIPS).All the WML patients were assessed with Stroop Color-Word Test,Trail Making Test, Symbol Digital Modalities Test, and Verbal Fluence Test.The correlation between the scores of CHIPS and the executive tests were analysed. Results There was no significant difference in age, gender, level of education, and cardiovascular disease risk factors among four groups(P>0.05),but there were significant differences in scores of MoCA and CHIPS(F>25.781,P<0.001),while the score of MoCA was the least(P<0.01)and the scores of CHIPS were the most in VaD group (P<0.001).The CHIPS scores of left and bilateral hemisphere negatively correlated with all the scores of execu-tive tests(P<0.05),while that of the right hemisphere just correlated with the scores of some executive tests(P<0.05). Conclusion For cognitive impairment after WML,cholinergic pathway damage may relate with the executive function impairment,especially the damage in left cerebral hemisphere.

Analysis of an Association between Single Nucleotide Polymorphisms of Vascular Endothelial Growth Factor Gene and Risk of Cerebral White Matter Lesion

BACKGROUND: Endothelial dysfunction is suggested to be one of the pathogenesis of cerebral white matter lesion (cWML). Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and integrity of vascular endothelial cell, and altered expression of VEGF gene induces vascular diseases including cerebrovascular diseases. The objective of this study is to investigate whether single nucleotide polymorphism (SNP) of VEGF gene confers an increased risk of cWML. METHODS: Total 337 study subjects without history of stroke were included. The presence and severity of cWML were measured on fluid-attenuated inversion recovery image. Genotypes of VEGF -2578G>A, -1154G>A, -634G>C and +936C>T were analyzed. RESULTS: Among 337 study subjects, cWML was found in 208 patients (62%), and fifty-eight cases (17%) of them had overt cWML. In univariate analysis, age, female sex and plasma total homocysteine level (tHcyt) were higher in the mild and overt cWML group than no cWML group (p<0.05). The percentage of previous history of hypertension and the value of systolic blood pressure were higher in overt cWML group than no cWML group. In univariate and logistic regression analysis, none of four tested VEGF SNPs was significantly different between control group, mild and overt cWML groups. There was no difference between plasma tHcyt levels and each VEGF SNPs in control group and cWML groups. CONCLUSIONS: In this study, old age, female sex, hypertension and plasma tHcyt were associated with cWML. However, we failed to find an association between cWML and VEGF gene polymorphism, which may indicate that genetic polymorphism of VEGF does not play a direct role in the pathogenesis of cWML.

Association between Single Nucleotide Polymorphisms of alpha2A-, alpha2B-, and alpha2C-Adrenergic Receptor Genes and Risk of Cerebral White Matter Lesion / 대한뇌졸중학회지

BACKGROUND: An alpha2-adrenergic receptor (alpha2-AR, ADRA2) mediates induction of hypotension and inhibition of lipolysis and insulin secretion. We evaluated whether single nucleotide polymorphisms (SNPs) of alpha2A (ADRA2A), alpha2B (ADRA2B), and alpha2C (ADRA2C) adrenergic receptors are associated with cerebral white matter lesion (cWML). METHODS: Total 336 study subjects who had no stroke were enrolled in this study. The Indices of cWML include total WML (TWML), periventricular WML (PVWML), and subcortical WML (SCWML) on brain fluid-attenuated inversion recovery (FLAIR) image. Common genetic variants of ADRA2A (1780G>A), ADRA2B (Ins/Del301-303), and ADRA2C (Ins/Del322-325) were examined. RESULTS: Among 336 study subjects, cWML was found in 66 patients (20%). In multivariate analysis, there were no significant effects of all tested ADRA2 polymorphisms on TWML. Significant association of ADRA2A 1780 AA genotype was found in PVWML (OR: 3.368, 95% CIs: 1.280-8.865, adjusted p-value after false discovery rate (FDR) correction=0.014) but not SCWML. CONCLUSION: Although SNPs of three ADRA2 subtypes failed to reach a significance in overall risk for cWML, the ADRA2A 1780G>A polymorphism may be associated with development of PVWML.

Progress in Ischemic White Matter Lesions / 国际脑血管病杂志

Head MRI and CT scans Can frequently find ischemic cerebral white matter lesions in healthy elderly and in patients with atherosclerosis.Ischemic cerebral white matter lesions are regarded as a manifestation of cerebral small vessel lesions.which Can result in symptoms such as cognitive impairment,and predict extraeranial or intracranial ischemic events.This article reviews the recent progress in research on cerebral white matter lesions.their pathogenesis and clirilcal significance.