老年脑梗死后血管性痴呆病人血清AGEs、RAGE水平与病情严重程度的关系

doi:10.3969/j.issn.1003-9198.2023.08.023

摘要/Abstract

摘要： 目的探讨老年脑梗死后血管性痴呆(CI-VD)病人血清晚期糖基化终末产物(AGEs)、晚期糖基化终末产物受体(RAGE)水平与病情严重程度的关系。方法选取2020年1月至2021年6月中国人民解放军中部战区总医院收治的96例老年CI-VD病人,另选取同期医院收治的84例老年单纯脑梗死(cerebral infarction, CI)病人,比较2组病人血清AGEs、RAGE水平。根据病情严重程度将老年CI-VD病人分为轻度组(n=25)、中度组(n=39)和重度组(n=32),比较3组病人血清AGEs、RAGE水平,采用Spearman秩相关分析血清AGEs、RAGE水平与病情严重程度的关系,采用Logistic回归分析老年CI-VD病人重度痴呆的影响因素,并采用ROC曲线分析血清AGEs、RAGE水平预测重度病情的价值。结果老年CI-VD病人血清AGEs、RAGE水平均高于老年单纯CI病人(P<0.01);血清AGEs、RAGE水平随着病情的加重而增加(P<0.05),Spearman相关性分析显示,血清AGEs(r=0.446,P<0.001)、RAGE(r=0.469,P<0.001)水平与病情严重程度呈正相关;多因素Logistic回归分析结果显示,受教育程度及血清神经元特异性烯醇化酶(NSE)、AGEs、RAGE水平均是影响老年CI-VD病人病情的独立相关因素(P<0.05);ROC曲线分析显示,老年CI-VD病人血清AGEs、RAGE预测重度痴呆的最佳截断值分别为33.07 μg/mL和550.31 μg/mL,两者联合预测重度病情的特异度和AUC分别为95.31%和0.855,高于单独预测价值(P<0.05)。结论老年CI-VD病人血清AGEs、RAGE水平与病情严重程度有关,临床检测其水平变化可作为预测病情变化的敏感指标。

关键词: 老年人, 脑梗死, 血管性痴呆, 晚期糖基化终末产物, 晚期糖基化终末产物受体

Abstract: Objective To investigate the relationship of serum advanced glycation end products (AGEs) and receptor of AGEs (RAGE) with dementia severity in the patients with vascular dementia after cerebral infarction. Methods A total of 96 elderly patients with vascular dementia after cerebral infarction (CI-VD group) and 84 elderly patients with simple cerebral infarction (CI group) who were admitted to the Central Theater Command General Hospital from January 2020 to June 2021 were enrolled. The serum levels of AGEs and RAGE were compared between the two groups. According to the severity of dementia, the CI-VD patients were divided into mild group (n=25), moderate group (n=39) and severe group (n=32), and the serum levels of AGEs and RAGE were compared among the three groups. Spearman correlation was used to analyze the correlation of serum AGEs and RAGE levels with disease severity. Multivariate Logistic regression analysis was used to analyze the influencing factors of the severity of dementia. Receiver operating characteristic (ROC) curve was used to analyze the value of serum AGEs and RAGE levels in predicting severe dementia in the elderly CI-VD patients. Results The serum levels of AGEs and RAGE in CI-VD group were higher than those in CI group (P<0.01), and significantly increased with the severity of dementia (P<0.05). Spearman correlation analysis showed that serum AGEs (r=0.446, P<0.001) and RAGE (r=0.469, P<0.001) were positively correlated with dementia severity. Multivariate Logistic regression analysis showed that education level, serum NSE, AGEs and RAGE levels were associated with the severity of dementia in the elderly CI-VD patients (P<0.05). ROC curve analysis showed that the optimal cut-off points of serum AGEs and RAGE levels for predicting the severity of dementia in elderly CI-VD patients were 33.07 μg/mL and 550.31 μg/mL, and the AUC of the combination of serum AGEs and RAGE levels was higher than that of AGEs or RAGE alone (P<0.05). Conclusions Serum levels of AGEs and RAGE are related to the severity of dementia in the elderly CI-VD patients, which can be used for predicting the severity of dementia.

Key words: aged, cerebral infarction, vascular dementia, advanced glycation end products, advanced glycation end products receptor

中图分类号:

R 749.13

刘丽娟, 江曼, 成勇, 毛高峰, 方煌. 老年脑梗死后血管性痴呆病人血清AGEs、RAGE水平与病情严重程度的关系[J]. 实用老年医学, 2023, 37(8): 853-857.

LIU Li-juan, JIANG Man, CHENG Yong, MAO Gao-feng, FANG Huang. Relationship of serum levels of AGEs and RAGE with dementia severity in elderly patients with vascular dementia after cerebral infarction[J]. Practical Geriatrics, 2023, 37(8): 853-857.

参考文献

[1] LIAO Z, BU Y, LI M, et al. Remote ischemic conditioning improves cognition in patients with subcortical ischemic vascular dementia [J]. BMC Neurol, 2019, 19(1):206-212.
[2] KAWADA T. Apolipoprotein E ε4 allele and vascular cognitive impairment no dementia (VCIND) after cerebral infarction [J]. J Neurol Sci, 2020, 21(3):227-238.
[3] 宋迎, 李晨. 多奈哌齐联合奥拉西坦治疗急性脑梗死后血管性痴呆的临床疗效[J]. 国际生物医学工程杂志, 2020, 43(1):46-49.
[4] CHO B P H, NANNONI S, HARSHFIELD E L, et al. NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants [J]. J Neurol Neurosurg Psychiatry, 2021, 92(7):694-701.
[5] ZENG Q, HUANG Z, WEI L, et al. Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction [J]. Neurol Sci, 2019, 40(5):1049-1054.
[6] CHEN J, MOOLDIJK S S, LICHER S, et al. Assessment of advanced glycation end products and receptors and the risk of dementia [J]. JAMA Netw Open, 2021, 4(1):3012-3018.
[7] RUNGRATANAWANICH W, QU Y, WANG X, et al. Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury [J]. Exp Mol Med, 2021, 53(2):168-188.
[8] CHOU P S, WU M N, YANG C C, et al. Effect of advanced glycation end products on the progression of Alzheimer's disease [J]. J Alzheimers Dis, 2019, 72(1):191-197.
[9] 中国卒中学会, 卒中后认知障碍管理专家委员会. 卒中后认知障碍管理专家共识[J]. 中国卒中杂志, 2017, 12(6):519-531.
[10] 贾建平. 中国痴呆与认知障碍诊治指南[M]. 北京:人民卫生出版社, 2010:102-103.
[11] KELLEHER J, DICKINSON A, CAIN S, et al. Patient-specific iPSC model of a genetic vascular dementia syndrome reveals failure of mural cells to stabilize capillary structures [J]. Stem Cell Reports, 2019, 13(5):817-831.
[12] 李光宗, 李靖, 朱晨, 等. 脑梗死后并发血管性痴呆的危险因素及血清VEGF、MMP-9的早期预测价值[J]. 中西医结合心脑血管病杂志, 2021, 19(5):836-839.
[13] 单连标, 魏巍, 王施, 等. 瑞舒伐他汀钙片联合多奈哌齐对脑梗塞合并血管性痴呆患者血管内皮功能及炎症的影响[J]. 川北医学院学报, 2020, 35(1):122-125.
[14] HADDAD M, PERROTTE M, BEN KHEDHER M R, et al. Levels of receptor for advanced glycation end products and glyoxalase-1 in the total circulating extracellular vesicles from mild cognitive impairment and different stages of Alzheimer's disease patients [J]. J Alzheimers Dis, 2021, 84(1):227-237.
[15] CHRYSANTHOU M, MIRO ESTRUCH I, RIETJENS I M C M, et al. In vitro methodologies to study the role of advanced glycation end products (AGEs) in neurodegeneration [J]. Nutrients, 2022, 14(2):363-372.
[16] TAKEUCHI M, SAKASAI-SAKAI A, TAKATA T, et al. Intracellular toxic AGEs (TAGE) triggers numerous types of cell damage[J]. Biomolecules, 2021, 11(3):387-394.
[17] 马宗艳, 蔡宏斌, 裴丽娟, 等. 血清晚期糖基化终末产物和可溶性晚期糖基化终末产物受体与阿尔茨海默病及血管性痴呆关系的研究[J]. 国际神经病学神经外科学杂志, 2019, 46(1):55-59.
[18] ATAÇ Z S, ALAYLIOĞLU M, DURSUN E, et al. G82S polymorphism of receptor for advanced glycation end products gene and serum soluble RAGE levels in mild cognitive impairment and dementia of Alzheimer's type patients in Turkish population [J]. J Clin Neurosci, 2019, 59(4):197-201.
[19] PRASAD K. AGE-RAGE stress: a changing landscape in pathology and treatment of Alzheimer's disease [J]. Mol Cell Biochem, 2019, 459(1/2):95-112.