教育与载脂蛋白E基因交互作用调节轻度认知障碍患者的认知功能和脑网络活性

Interaction between education and apolipoprotein E genotype on regulating cognitive function and brain network activity in patients with mild cognitive impairment

摘要:

目的 受教育水平和载脂蛋白E（apolipoprotein E，ApoE）基因均可影响认知障碍的发生，但两者的交互作用尚不明确。本研究旨在探讨受教育水平和ApoE基因对轻度认知障碍（mild cognitive impairment，MCI）患者的认知功能和默认网络（default mode network，DMN）的交互作用。方法 本研究数据来源于阿尔茨海默病神经影像学计划数据集。根据受教育水平和ApoE ε4等位基因（ApoE ε4，ApoE4）状态将MCI受试者分为4组，运用协方差法分析两者对认知功能和DMN的作用。结果 教育和ApoE基因型对MCI患者整体认知功能存在显著交互作用（P<0.05）：在低教育受试者中，非ApoE4携带者的整体认知功能优于携带者［23.00（22.50，25.50） vs. 22.00（21.00，24.00）］，而在高教育受试者中则相反［23.00（22.00，26.00） vs. 25（22.75，26.25）］。另一方面，受教育水平与ApoE基因型对DMN的左侧颞中回的功能连接值（functional connectivity，FC）存在显著交互作用（P<0.05）：在低教育受试者中，ApoE4携带者的FC显著高于非携带者（0.35±0.32 vs. 0.15±0.28），而在高教育受试者中则相反（0.09±0.26 vs. 0.25±0.23）。行为学关联分析发现左侧颞中回的FC与整体认知功能呈显著负相关（r=-0.560，P=0.030）。结论 高教育水平显著降低ApoE4等位基因对MCI患者认知功能的破坏作用，该认知保护作用可能与高教育水平降低异常的DMN活性相关。该结果强调基因与环境交互作用对认知障碍的重要影响。

Abstract:

Objective Although both education and apolipoprotein E（ApoE） gene affect the risk of cognitive impairment，whether there is an interaction between them is still unclear. This study aimed to explore the effects and interaction of education level and ApoE genotype on cognitive function and default mode network（DMN） in patients with mild cognitive impairment（MCI）.Methods The study was based on the Alzheimer's Disease Neuroimaging Initiative dataset. According to the level of education and the carrier status of ApoE ε4（ApoE4） allele，MCI subjects were divided into four groups. The effects of education level and ApoE genotype on cognitive function and the DMN were analyzed by using the covariance model.Results There was a significant interaction between education and ApoE genotype on the global cognitive function of MCI patients（P<0.05）. Specifically，in subjects with low education level，the global function of non-ApoE4 carriers was better than that of carriers［23.00（22.50，25.50） vs. 22（21，24）］，while in subjects with high education level，it was opposite［23.00（22.00，26.00） vs. 25.00（22.75，26.25）］. On the other hand，education level and ApoE genotype also had a significant interaction on the functional connectivity（FC） of the left middle temporal gyrus of DMN（P<0.05）. Among subjects with low education level，the FC of ApoE4 carriers was significantly higher than that of non-carriers（0.35±0.32 vs. 0.15±0.28），while it was opposite in subjects with high education level（0.09±0.26 vs. 0.25±0.23）. Behavioral correlation analysis showed that the FC of the left middle temporal gyrus was negatively correlated with the global function（r=-0.560，P=0.030）.Conclusion High education level can significantly reduce the damage effect of ApoE4 allele on cognitive function of MCI patients，which may be related to the reduction of abnormal DMN FC of ApoE4 carriers by high education level. These results support that the interaction between genes and the environment plays an important role in regulating the occurrence of cognitive impairment.