脑小血管病所致认知功能障碍与血清脑源性神经营养因子水平的相关性

doi:10.3969/j.issn.1673-5765.2021.04.010

摘要/Abstract

摘要：

目的分析脑小血管病（cerebral small vessel diseases，CSVD）所致认知功能障碍与脑源性神经营养因子（brain derived neurotrophic factor，BDNF）水平的相关性。方法前瞻性纳入2019年4月-2020年4月连续就诊于新乡医学院第一附属医院的CSVD患者为研究对象。根据MMSE评分将其分为认知功能正常组（27～30分）、轻度认知功能障碍组（21～26分）及中度认知功能障碍组（10～20分），比较三组基线资料及血清BDNF水平，分析BDNF水平与认知功能的相关性。结果最终纳入60例CSVD患者，平均年龄60.6±10.5岁，男性38例（63.3%）；其中认知功能正常组 21例（35.0%）、轻度认知功能障碍组24例（40.0%）、中度认知功能障碍组15例（25.0%）。三组间年龄、受教育年限、BDNF水平差异均有统计学意义。Pearson相关性分析结果显示，血清BDNF水平、受教育年限与MMSE评分呈正相关（r =0.499，P =0.043；r＝0.516，P＜0.001），年龄与MMSE评分呈负相关（r =-0.577，P＜0.001）。结论 CSVD所致认知功能障碍与血清BDNF水平存在相关性，即血清BDNF水平越低，认知功能损害程度越重。

文章导读： 血清BDNF水平与CSVD认知功能障碍程度密切相关，该指标有望作为CSVD后认知功能障碍辅助诊断和判断严重程度的生物学标志物。

关键词: 脑小血管病; 认知功能障碍; 脑源性神经营养因子

Abstract:

Objective To explore the relationship between the level of serum brain derived neurotrophic factor (BDNF) and cognitive impairment due to cerebral small vessel disease (CSVD). Methods The prospective study enrolled the patients with CSVD who were consecutively admitted to the First Affiliated Hospital of Xinxiang Medical University from April 2019 to April 2020. According to the MMSE score, all the patients were divided into normal cognitive function group (27-30 points), mild cognitive impairment group (21-26 points) and moderate cognitive impairment group (10-20 points). The baseline data and serum BDNF level were compared among the three groups, and the correlation between the level of serum BDNF and cognitive function was analyzed. Results A total of 60 patients with CSVD were included, with an average age of 60.6±10.5 years old and 38 males (63.3%), and including 21 (35.0%) cases with normal cognitive function, 24 (40.0%) with mild cognitive impairment and 15 (25.0%) with moderate cognitive impairment. There were statistical differences in age, education attainment and the level of serum BDNF among the three groups. The Pearson correlation analysis showed that the level of serum BDNF and educational attainment were both positively correlated with MMSE score (r =0.499, P =0.043; r =0.516, P <0.001), while the age was negatively correlated with MMSE score (r =-0.577, P <0.001). Conclusions The level of serum BDNF was correlated with cognitive impairment due to cerebrovascular disease. The lower the serum BDNF level, the more severe the cognitive impairment.

Key words: Cerebral small vessel disease; Cognitive impairment; Brain derived neurotrophic factor

孟利芳*，彭雪*，刘昊，王瑾，刘俊丽，贾祥磊，赵盼盼，王凡，王超伟，张黎军，李青，吉四辈，袁彬，蔡瑞艳，杨如，李少敏，赵建华（*第一作者）. 脑小血管病所致认知功能障碍与血清脑源性神经营养因子水平的相关性[J]. 中国卒中杂志, 2021, 16(04): 371-375.

MENG Li-Fang, PENG Xue, LIU Hao, WANG Jin, LIU Jun-Li, JIA Xiang-Lei, ZHAO Pan-Pan,WANG Fan, WANG Chao-Wei, ZHANG Li-Jun, LI Qing, JI Si-Bei, YUAN Bin, CAI Rui-Yan, YANG Ru, LI Shao-Min,ZHAO Jian-Hua. Correlation between Serum Brain Derived Neurotrophic Factor Level and Cognitive Impairment due to Cerebral Small Vessel Disease[J]. Chinese Journal of Stroke, 2021, 16(04): 371-375.

参考文献

[1] PANTONI L. Cerebral small vessel disease：from

pathogenesis and clinical characteristics to

therapeutic challenges[J]. Lancet Neurol，2010，9 （7）：689-701.

[2] WARDLAW J M，SMITH C，DICHGANS M.

Small vessel disease：mechanisms and clinical

implications[J]. Lancet Neurol，2019，18（7）：684-

696.

[3] PENG D T，Geriatric Neurology Group，Chinese

Society of Geriatrics；Clinical Practice Guideline

for Cognitive Impairment of Cerebral Small Vessel

Disease Writing Group. Clinical practice guideline

for cognitive impairment of cerebral small vessel

disease[J]. Aging Med，2019，2（2）：64-73.

[4] BOS D，WOLTERS F J，DARWEESH S K L，et

al. Cerebral small vessel disease and the risk of

dementia：a systematic review and meta-analysis of

population-based evidence[J]. Alzheimers Dement，

2018，14（11）：1482-1492.

[5] NICULESCU D，MICHAELSEN-PREUSSE K，

GÜNER Ü，et al. A BDNF-mediated push-pull

plasticity mechanism for synaptic clustering[J]. Cell

Rep，2018，24（8）：2063-2074.

[6] 中华医学会神经病学分会. 中国脑小血管病诊治共

识[J]. 中华神经科杂志，2015，48（10）：838-844.

[7] 中国医师协会神经内科分会认知障碍专业委员会，

《中国血管性认知障碍诊治指南》编写组. 2019年中

国血管性认知障碍诊治指南[J]. 中华医学杂志，2019，

99（35）：2737-2744.

[8] 中华医学会老年医学分会老年神经病学组，脑小血

管病认知功能障碍诊疗指南中国撰写专家组. 脑小

血管病相关认知功能障碍中国诊疗指南（2019）[J].

中华老年医学杂志，2019，38（4）：345-354.

[9] KALARIA R N. Small vessel disease

and Alzheimer's dementia：pathological

considerations[J]. Cerebrovasc Dis，2002，13（2）：

48-52.

[10] MENG L F，ZHAO J H，LIU J L，et al. Cerebral

small vessel disease and cognitive impairment[J].

Neuroretoratology，2019，7（4）：184-195.

[11] 高鸣，陈娇，赵倩倩，等. 血清S100β蛋白水平与脑小

血管病患者非痴呆型血管性认知障碍的相关性研究

[J]. 中国卒中杂志，2018，13（11）：1153-1157.

[12] GRAU-OLIVARES M，ARBOIX A. Mild cognitive

impairment in stroke patients with ischemic cerebral

small-vessel disease：a forerunner of vascular

dementia?[J]. Expert Rev Neurother，2009，9（8）：

1201-1217.

[13] GONZALEZ M C，RADISKE A，CAMMAROTA

M. On the involvement of BDNF signaling in

memory reconsolidation[J/OL]. Front Cell Neurosci，

2019，13：383[2020-07-10]. https：//doi.org/10.3389/

fncel.2019.00383.

[14] LU B，NAGAPPAN G，LU Y. BDNF and synaptic

plasticity，cognitive function，and dysfunction[J/OL].

Handb Exp Pharmacol，2014，220：223-250[2020-

07-10]. https：//doi.org/10.1007/978-3-642-45106-5_9.

[15] VIGNOLI B，BATTISTINI G，MELANI R，et

al. Peri-synaptic glia recycles brain-derived

neurotrophic factor for LTP stabilization and

memory retention[J]. Neuron，2016，92（4）：873-

887.

[16] PANG P T，LU B. Regulation of late-phase LTP and

long-term memory in normal and aging hippocampus：

role of secreted proteins tPA and BDNF[J]. Ageing

Res Rev，2004，3（4）：407-430.

[17] REZAEI S，ASGARI MOBARAKE K，SABERI

A，et al. Brain-derived neurotrophic factor（BDNF）

Val66Met polymorphism and post-stroke dementia：a

hospital-based study from northern Iran[J]. Neurol

Sci，2016，37（6）：935-942.

[18] HASSAN T M，YARUBE I U. Peripheral

brain-derived neurotrophic factor is reduced in

stroke survivors with cognitive impairment[J].

Pathophysiology，2018，25（4）：405-410.

[19] SILVESTRINI M，VITICCHI G，ALTAMURA

C，et al. Cerebrovascular assessment for the risk

prediction of Alzheimer's disease[J]. J Alzheimers

Dis，2012，32（3）：689-698.

[20] HILAL S，MOK V，YOUN Y C，et al. Prevalence，

risk factors and consequences of cerebral small

vessel diseases：data from three Asian countries[J].

J Neurol Neurosurg Psychiatry，2017，88（8）：669-

674.