脑小血管病患者外周血同型半胱氨酸水平与认知功能的相关性研究

doi:10.3969/j.issn.1673-5765.2019.02.003

摘要/Abstract

摘要：

目的 HHcy是脑血管病和认知功能障碍的危险因素之一。本文拟明确脑小血管病（small vessel disease，SVD）患者外周血Hcy水平与早期认知功能损害的相关性及其机制。方法连续入组缺血性卒中后门诊随访的非痴呆SVD患者，登记人口社会学、血管危险因素等资料，进行全面认知评估。入组1周内采集空腹静脉血检测Hcy，根据血浆Hcy水平将SVD患者分为HHcy组（Hcy＞15 μmmol/L）和正常Hcy（normal Hcy，NHcy）组（Hcy≤15 μmmol/L）。2周内行多模式头颅MRI检查。对2组患者的认知评分及影像特点进行比较，并与Hcy水平进行相关性分析。结果 ①研究共纳入81例SVD患者，平均年龄（64.3±7.4）岁；男性65例，占80.2%；轻度认知障碍50例，占61.7%。②HHcy组30例（37.0%），NHcy组51例（63.0%）。HHcy组吸烟比例高于NHcy组。 ③HHcy组执行功能中交替连线测验B（trail making test B，TMT-B）耗时数高于NHcy组（P =0.016），数字符号转换测验（digital symbol substitution test，DSST）（P =0.013）、数字广度测验（digital span test， DS）顺背（P =0.029）得分低于NHcy组。④HHcy组较NHcy组中重度脑室旁白质病变（63.3% vs 39.2%， P =0.018）、深部白质病变（60.0% vs 37.3%，P =0.036）和多发微出血（36.7% vs 17.3%，P =0.047）的比例更高，且Hcy水平与脑室旁白质病变评分显著相关（r =0.227，P =0.041）。⑤经脑室旁白质病变评分校正后，Hcy水平与TMT-B耗时数（r =0.278，P =0.013）正相关，与DSST（r =-0.354，P =0.004）和DS 顺背（r =-0.366，P =0.001）得分负相关。结论 SVD患者外周血Hcy水平与执行注意以及脑室旁白质病变严重程度显著相关，外周血Hcy水平可能是SVD早期认知功能障碍的生物标志物之一。

文章导读： 作者对脑小血管病患者外周血Hcy水平与认知功能损害进行相关分析，发现Hcy水平与执行注意以及脑室旁白质病变严重程度显著相关，外周血Hcy水平可能是脑小血管病早期认知障碍的生物标志物之一。

关键词: 脑小血管病; 高同型半胱氨酸血症; 认知功能; 神经影像

Abstract:

Objective HHcy is one of the independent risk factors for either cerebrovascular disease or cognitive impairment. The aim of this study is to investigate the relationship between blood Hcy level and early cognitive impairment in small vessel disease (SVD). Methods The data of SVD patients with no dementia from stroke clinic in our hospital for poststroke follow-up were consecutively collected. The data included demographic information, vascular risk factors (VRFs) spectrum, cognitive assessment results and etc. The fasting blood Hcy was measured within 1 week after enrollment. HHcy was defined as plasma Hcy level higher than 15 μmol/L. According to the Hcy test results, the patients were divided into HHcy group (Hcy>15 μmmol/L) and normal homocysteine (NHcy) group (Hcy≤15 μmol/L). Multimodal MRI was performed in all patients within 2 weeks after enrollment. The cognitive scores and imaging feature between the two groups were compared. The correlations of Hcy level with cognitive assessment results as well as with the imaging indices were analyzed. Results (1) A total of 81 SVD patients were enrolled in this study, with average age (64.3±7.4) years old, 65 male patients (80.2%) and 50 patients (61.7%) with mild cognitive impairment. (2) 30 patients (37.0%) in HHcy group and 51 ones (63.0%) in NHcy group. There were more smoking patients in HHcy than in NHcy group. There were no significant difference in age, gender, education years between the two groups. (3) There were significant difference in the attentionexecutive function assessment such as trail making test B (TMT-B) (P =0.016), digital symbol substitution test (DSST) (P =0.013) and forward digital span test (DS-forward) (P =0.029) scores between the two groups. (4) The proportion of moderate to severe periventricular white matter lesions (PV-WMLs) (63.3% vs 39.2%, P =0.018), deep WMLs (60.0% vs 37.3%, P =0.036) and multiple cerebral microbleedings (CMBs) (36.7% vs 17.3%, P =0.047) in HHcy group were higher than those in NHcy group. The blood Hcy level was correlated with PV-WMLs (r =0.227, P =0.041). (5) After adjusting for PV-WMLs score, Hcy level was positively correlated with TMT-B time (r =0.278, P =0.013), negatively correlated with DSST (r =-0.354, P =0.004) and DS-forward (r =-0.366, P =0.001). Conclusions The blood Hcy level in SVD was significantly correlated with attention-executive function and PV-WMLs. The blood Hcy level might be one of the markers of early cognitive impairment in SVD.

Key words: Small vessel disease; Hyperhomocysteinemia; Cognition; Neuroimaging

卢东，赵薇，杜静，耿介立，汪耀，曹雯炜，俞羚，支楠，周滟，徐群. 脑小血管病患者外周血同型半胱氨酸水平与认知功能的相关性研究[J]. 中国卒中杂志, 2019, 14(02): 100-105.

LU Dong, ZHAO Wei, DU Jing, GENG Jie-Li, WANG Yao, CAO Wen-Wei, YU Ling, ZHI Nan,ZHOU Yan, XU Qun. Study on the Correlation between Blood Homocysteine Level and Cognitive Function in Patients with Cerebrovascular Disease[J]. Chinese Journal of Stroke, 2019, 14(02): 100-105.

参考文献

[1] BISWANJAN R，MEENA A，AKHTER M S，et al.

Homocystine levels，polymorphisms and the risk of

ischemic stroke in young Asian Indians[J]. J Stroke

Cerebrovasc Dis，2009，18（2）：103-110.

[2] FENG C，BAI X，XU Y，et al.

Hyperhomocysteinemia associates with small

vesseldisease more closely than large vessel

disease[J]. Int J Med Sci，2013，10（4）：408-412.

[3] OKROGLIC S，WIDMANN C N，URBACH H，et

al. Clinical symptoms and risk factors in cerebral

microangiopathy patients[J/OL]. PLoS One，2013，

8（2）：e53455. https：//doi.org/10.1371/journal.

pone.0053455.

[4] TAY L，LIM W S，CHAN M，et al. New DSM-V

neurocognitive disorders criteria and their impact

on diagnostic classifications of mild cognitive

impairment and dementia in a memory clinic

setting[J]. Am J Geriatr Psychiatry，2015，23（8）：

768-779.

[5] STEINER G Z，MATHERSUL D C. A Systematic

Review of Intervention Studies Examining

Nutritional and Herbal Therapies for Mild

Cognitive Impairment and Dementia Using

Neuroimaging Methods：Study Characteristics and Intervention Efficacy[J/OL]. Evid Based

Complement Alternat Med，2017，608629. https：//

doi.org/10.1155/2017/6083629.

[6] 曹雯炜，赵薇，俞羚，等. 脑小血管病患者认知状态

与神经影像学特征的相关性分析[J]. 神经病学与神

经康复学杂志，2017，19（1）17-24.

[7] 郭起浩，孙一忞，袁晶，等. 8种执行功能测验在上海

社区老年人中的应用[J]. 中国行为医学科学，2007，

16（7）：628-631.

[8] LEE S H，BAE H J，KO S B，et al. Comparative

analysis of the spatial distribution and severity of

cerebral microbleeds and old lacunes[J]. J Neurol

Neurosurg Psychiatry，2004，75（3）：423-427.

[9] GREGOIRE S M，CHAUDHARY U J，BROWN

M M，et al. The Microbleed Anatomical Rating

Scale（MARS）：reliability of a tool to map brain

microbleeds[J]. Neurology，2009，73（21）：1759-

1766.

[10] FAZEKAS F，CHAWLUK J B，ALAVI A，et al. MR

signal abnormalities at 1.5 T in Alzheimer's dementia

and normal aging[J]. AJR Am J Roentgenol，1987，

149（2）：351-356.

[11] SESHADRI S，WOLF P A，BEISER A S，et al.

Association of plasma total homocysteine levels with

subclinical brain injury：cerebral volumes，white

matter hyperintensity，and silent brain infarcts

at volumetric magnetic resonance imaging in the

Framingham Off spring Study[J]. Arch Neurol，2008，

65（5）：642-649.

[12] SESHADRI S，BEISER A，SELHUB J，et al.

Plasma homocysteine as a risk factor for dementia

and Alzheimer's disease[J]. N Engl J Med，2002，346

（7）：476-483.

[13] IORIO M，SPALLETTA G，CHIAPPONI C，et

al. White matter hyperintensities segmentation：a

new semi-automated method[J/OL]. Front Aging

Neurosci，2013，5：76. https：//doi.org/10.3389/

fnagi.2013.00076.

[14] 张金，郝冬琳，何国平. 腔隙性脑梗死患者脑微出血

与血清同型半胱氨酸的相关性研究[J]. 中国临床神

经科学，2014，22（4）：389-392，401.

[15] WANG T，SUN Z W，SHAO L Q，et al. Diagnostic

Values of Serum Levels of Homocysteine and

Uric Acid for Predicting Vascular Mild Cognitive

Impairment in Patients with Cerebral Small Vessel

Disease[J/OL]. Med Sci Monit，2017，23：2217-2225.

PMID：28489814，https：//www.ncbi.nlm.nih.gov/

pmc/articles/PMC5436427/.

[16] DUTHIE S J，WHALLEY L J，COLLINS A R，et

al. Homocysteine，B vitamin status，and cognitive

function in the elderly[J]. Am J Clin Nutr，2002，75

（5）：908-913.

[17] SACHDEV P，PARSLOW R，SALONIKAS C，et

al. Homocysteine and the brain in midadult life：

evidence for an increased risk of leukoaraiosis in

men[J]. Arch Neurol，2004，61（9）：1369-1376.