Abstract: Objective  To investigate the differences in clinical characteristics among various apolipoprotein E (APOE) genotypes in patients with acute ischemic stroke, and to explore the association between APOE gene polymorphism and changes in cognitive function after stroke. 
Methods  This study was based on a multicenter, prospective study (predictive, preventive and personalized project of vascular cognitive impairment in China). Patients with acute ischemic stroke admitted to six medical institutions in China from September 1, 2022 to August 31, 2023 were enrolled. Baseline data collected at enrollment included age, sex, years of education, BMI, medical history (hypertension, diabetes mellitus, heart disease, hyperlipidemia, stroke or TIA), smoking history, drinking history, medication history, NIHSS score, MoCA score, Hamilton depression scale (HAMD) score, Hamilton anxiety scale (HAMA) score, imaging data (whether critical site infarction, infarct size grade), TOAST classification, and APOE genotype. Patients were categorized into three groups based on their APOE genotypes: APOE ε3 homozygotes (ε3/ε3), APOE ε2 carriers (ε2/ε3, ε2/ε2), and APOE ε4 carriers (ε3/ε4, ε4/ε4). The patients were followed up 6 to 12 months after stroke onset. One-factor analysis of variance was performed to compare the above baseline clinical data among the three groups. Additionally, generalized linear mixed models were utilized to analyze the correlation between APOE genotypes and the longitudinal changes in MoCA scores after stroke. 
Results  A total of 202 patients with acute ischemic stroke were included at baseline, including 155 males and 47 females, with a mean age of (58.5±10.4) years. There were no statistically significant differences in baseline age, sex, years of education, BMI, medical history, smoking history, drinking history, medication history, NIHSS score, MoCA score, HAMD score, HAMA score, proportion of critical site infarction, infarct size grade, or TOAST classification among the three groups of patients with different APOE genotypes (all P>0.05). A total of 151 patients completed the follow-up, and the median follow-up period was 8.0 (7.0-10.0) months. After adjusting for sex, age, years of education, and center effect, it was found that compared with the APOE ε3 homozygotes, the APOE ε4 carriers showed a significant negative correlation with MoCA score at baseline (β=-1.682, P=0.029), and the interaction between follow-up period and APOE ε4 carrier status was also significantly negatively correlated with MoCA score (β=-0.322, P<0.001). 
Conclusions  The polymorphism of the APOE gene is related to the changes in cognitive function scores after stroke. Compared with the APOE ε3 homozygotes, APOE ε4 carriers exhibit lower cognitive function scores at stroke onset, and show a more rapid decline in cognitive function scores after stroke.

Key words: Acute ischemic stroke; Cognitive function; Apolipoprotein E; Gene polymorphism

摘要： 目的 分析不同载脂蛋白E（apolipoprotein E，APOE）基因型急性缺血性卒中患者的临床特征差异，探讨APOE基因多态性与卒中后认知功能变化的相关性。
方法 本研究基于多中心、前瞻性的中国血管性认知障碍预测、预防和个性化研究，纳入2022年9月1日—2023年8月31日中国6家医疗机构收治的急性缺血性卒中患者，收集入组患者基线期年龄、性别、受教育年限、BMI、既往史（高血压、糖尿病、心脏病、高脂血症、卒中或TIA）、吸烟史、饮酒史、药物治疗史、NIHSS评分、MoCA评分、汉密尔顿抑郁量表（Hamilton depression scale，HAMD）评分、汉密尔顿焦虑量表（Hamilton anxiety scale，HAMA）评分、影像学资料（是否关键部位梗死、梗死体积分级）、TOAST分型，以及APOE基因型。根据APOE基因型，将患者分为APOE ε3纯合子（ε3/ε3）、APOE ε2携带者（ε2/ε3、ε2/ε2）和APOE ε4携带者（ε3/ε4、ε4/ε4）3组，并在发病后6～12个月对患者进行随访。对3组患者上述基线期临床资料进行单因素方差分析，采用广义线性混合模型分析APOE基因型与卒中后MoCA评分纵向变化的相关性。
结果 本研究在基线期共纳入急性缺血性卒中患者202例，其中男性155例、女性47例，年龄（58.5±10.4）岁。3组不同APOE基因型患者的基线期年龄、性别、受教育年限、BMI、既往史、吸烟史、饮酒史、药物治疗史、NIHSS评分、MoCA评分、HAMD评分、HAMA评分、关键部位梗死比例、梗死体积分级及TOAST分型的组间差异均无统计学意义（均P>0.05）。共151例患者完成随访，中位随访时间为8.0（7.0～10.0）个月。校正性别、年龄、受教育年限和中心效应后发现，与APOE ε3纯合子相比，APOE ε4携带者与基线期MoCA评分呈负相关（β=-1.682，P=0.029），随访时间和APOE ε4携带者的交互作用与MoCA评分呈负相关（β=-0.322，P<0.001）。
结论 APOE基因多态性与卒中后认知功能评分的变化有关，与APOE ε3纯合子相比，APOE ε4携带者在卒中时认知功能评分更低，且卒中后认知功能评分下降速度更快。

关键词: 急性缺血性卒中; 认知功能; 载脂蛋白E; 基因多态性