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

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.