認知正常老年人之教育程度減輕失智症高風險基因於反應抑制之負面效果

Abstract

載脂蛋白基因（Apolipoprotein E, ApoE）的ε4基因型是影響認知老化的重要因素。過去研究發現攜帶ε4基因型的認知正常老年人在執行功能上的表現較非攜帶者差，然而有些研究並無觀察到此差異。研究結果的不一致可能來自於測量執行功能的方法差異，且此差異使得比較不同執行功能成分有困難。另一方面，認知存量被認為會降低個體受大腦病理變化之影響，亦可能降低ApoE ε4造成的認知老化效果。本研究藉由完整的執行功能評估探討ε4基因型在反應抑制、轉換、工作記憶以及抽象推理四個執行功能成分表現上之負面影響。並藉由教育程度作為評量認知存量的指標，探究認知存量高低是否影響ε4基因型在認知老化的負面影響。本研究收集51位認知正常老年人的ApoE基因型、受教育年數、執行功能測驗表現。受試者依照ε4基因型分組，再做認知存量高低的次分組，並比較不同組別在四個執行功能成分的表現是否有差異。結果並無觀察到ε4基因型在執行功能表現上的主要效果。然而在ε4基因型及認知存量的分組上，ε4陽性低認知存量組在反應抑制成分的表現顯著低於ε4陰性高認知存量以及低認知存量組，反之ε4陽性高認知存量組的表現與兩ε4陰性組相當。此外，認知存量在抽象推理表現上有主要效果。研究結果顯示，相較於轉換、工作記憶以及抽象推理成分，反應抑制在探究先天因素及後天教育影響時扮演重要的角色。

Apolipoprotein E epsilon 4 (ApoE-ε4) has been associated with individual difference in cognitive aging. Previous studies have reported that possessing the ApoE ε4 allele adversely influenced the performances of executive functions (EFs) in late adulthood; however, results were inconsistent. Methodological differences may account for the inconsistency. Furthermore, cognitive reserve (CR), which explained the individual differences in susceptibility to brain changes, may also modulate the negative ε4 effect. The present study aimed to examine the potential negative effects of ApoE ε4 allele on four components of EFs, namely switching, working memory, inhibition, and abstract reasoning. We further investigated whether a higher education attainment, a common proxy measure for CR, could alleviate the adverse effect of ApoE ε4 allele on EFs. In present study we recruited 51 cognitively intact older adults. Participants were divided into groups by possessing ε4 allele (ε4+) or not (ε4-) and subgroups by high CR (HCR) or low CR (LCR). Results showed that although no main effect of ApoE genotype was observed across the four EF components, the potentially adverse ε4 effect on inhibition component was alleviated by higher education attainment. Specifically, the ε4+ LCR group had a significantly lower performance on the inhibition domain than ε4- HCR and LCR groups, whereas the performance of ε4+ HCR group was comparable to the two ε4- groups. A main effect of CR on abstract reasoning component was also observed. In this study, we heighten the distinctive role of response inhibition in the gene-environment interaction.