脑小血管病患者血清GDNF水平与神经影像学改变、认知功能障碍的相关性  

Correlation between serum GDNF level and neuroimaging changes and cognitive impairment in patients with cerebral small vessel disease

作　　者：杨方利 刘昊 王凡 李青[1] 陈希妍[1] 蔡瑞艳[1] 吴清武[2] 张健[2] 吉四辈[1] 路承彪[3] 李少敏 赵建华[1] Yang Fangli;Liu Hao;Wang Fan;Li Qing;Chen Xiyan;Cai Ruiyan;Wu Qingwu;Zhang Jian;Ji Sibei;Lu Chengbiao;Li Shaomin;Zhao Jianhua(Neurology Department of First Affiliated Hospital of Xinxiang Medical University,Henan Joint International Research Laboratory of Neurorestoratology for Senile Dementia,Henan Key Laboratory of Neurorestoratology,Xinxiang 453100,China;Imaging Department,First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,China;Department of Physiology and Neurobiology,Xinxiang Medical University,Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province,Xinxiang 453003 China;Ann Romney Center for Neurologic Diseases,Brigham and Women’s Hospital,Harvard Medical School,Boston,Massachusetts 02115,United States)

机构地区：[1]新乡医学院第一附属医院神经内科,河南省神经修复重点实验室,河南省老年性痴呆神经修复国际联合实验室,新乡453100 [2]新乡医学院第一附属医院影像科,新乡453100 [3]新乡医学院生理学与神经生物学教研室,河南省无创性神经调制国际联合实验室,新乡453003 [4]美国哈佛大学医学院布莱根妇女医院神经疾病研究中心,波士顿02115

出　　处：《中华行为医学与脑科学杂志》2023年第9期809-815,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金(81771517);河南省自然科学基金(182300410389);河南省科技厅科技攻关计划国际合作项目(232102521029)。

摘　　要：目的探讨脑小血管病(cerebral small vascular disease,CSVD)患者血清胶质细胞源性神经营养因子(glial cell-derived neurotrophic factor,GDNF)水平与其神经影像学改变及认知功能障碍的相关性。方法通过神经影像学筛查,招募2021年9月至2022年7月来新乡医学院第一附属医院神经内科住院的CSVD患者135名,进行了基本资料统计、头颅多模态磁共振检查及蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA),并通过酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测所有入组患者的血清GDNF浓度,通过入组患者GDNF浓度的中位数将入组人群分为低GDNF组及高GDNF组,通过Mann-WhitneyU检验、卡方检验、Logistic回归、Kruskal-WallisH检验和Jonckheere-Terpstra趋势检验等比较两组患者的基线资料、MoCA评分及各影像标记物,并分析脑小血管病患者血清GDNF水平与各影像标记物及认知功能的相关性。结果所有CSVD患者血清GDNF浓度的中位数为16.66 pg/mL。多因素logistic回归分析表明,低血清GDNF水平是CSVD患者脑白质高信号及影像总负荷的危险因素;多元logistic回归分析显示,血清GDNF水平是CSVD认知功能障碍保护性因素,血清GDNF水平预测CSVD患者认知功能障碍ROC曲线分析的曲线下面积为0.735,敏感度为66.4%,特异度为71.4%,且血清GDNF水平与视空间与执行功能、注意力和计算力、延迟回忆、定向力呈正相关(r=0.267,0.187,0.219,0.215,均P<0.05)。结论 CSVD患者血清GDNF水平与脑白质高信号、影像总负荷及认知功能障碍相关,血清GDNF水平对CSVD及其导致的认知功能障碍起到预测作用。Objective To investigate the relationship between serum glial cell line-derived neurotrophic factor(GDNF)levels and neuroimaging changes and cognitive impairment in patients with cerebral small vascular disease(CSVD).Methods 135 patients with CSVD recruited from the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from September 2021 to July 2022 were assessed by cranial multimodal magnetic resonance imaging and Montreal cognitive function assessment(MoCA),and the basic data were analyzed at the same time.The serum GDNF concentration of all patients was detected by enzyme-linked immunosorbent assay(ELISA).According to the median GDNF concentration,the patients were divided into low GDNF group and high GDNF group.The baseline data,MoCA score and imaging markers of the two groups were compared by Mann-Whitney U test,chi-square test,logistic regression,Kruskal-Wallis H test and Jonckheere-Terpstra trend test,and the correlation between serum GDNF level and imaging markers and cognitive function of patients with CSVD was analyzed.Results The median serum GDNF concentration of all CSVD patients was 16.66 pg/mL.Multivariate logistic regression analysis showed that low serum GDNF level was a risk factor for white matter hyperintensity and total image load in patients with CSVD.Serum GDNF level was a protective factor of cognitive impairment in patients with CSVD in multiple logistic regression analysis.The area under the curve of ROC curve analysis of cognitive impairment after CSVD predicted by serum GDNF level was 0.735,the sensitivity was 66.4%,and the specificity was 71.4%.The level of serum GDNF was positively related with visual space and executive function,attention and computational power,delayed recall and orientation(r=0.267,0.187,0.219,0.215,all P<0.05).Conclusion The serum GDNF level is related to white matter hyperintensities,total imaging load and cognitive impairment in patients with CSVD.Serum GDNF level may play a predictive role in CSVD and cognitive impairment.

关 键 词：脑小血管病 胶质细胞源性神经营养因子 认知功能障碍 磁共振成像 影像总负荷 

分 类 号：R743[医药卫生—神经病学与精神病学]