Laboratory of Social Cognitive Neuroscience, IDOCAL, University of Valencia, Valencia, Spain.
Laboratory of Social Cognitive Neuroscience, IDOCAL, University of Valencia, Valencia, Spain; Department of Psychology and Sociology, Area of Psychobiology, University of Zaragoza, Teruel, Spain; Aragon Health Research Institute, Aragon, Spain.
Neurobiol Learn Mem. 2018 Nov;155:297-305. doi: 10.1016/j.nlm.2018.08.013. Epub 2018 Aug 18.
The Apolipoprotein E4 (ApoE-ε4) allele has been suggested as the main risk factor for late onset Alzheimer's disease (AD), whereas the ApoE-ε2 allele has been proposed as a protective factor. These proposals have increased the interest in the effect of the ApoE genotype in healthy people. Additionally, high cortisol levels have been related to negative effects on cognition. However, few studies have investigated the relationship between cognitive performance and cortisol, taking into account the different ApoE alleles. For this reason, the aim of this study was to evaluate different cognitive domains (declarative and working memory, attention, and executive function) and their relationship with cortisol, considering the ApoE-ε2, ApoE-ε3, and ApoE-ε4 alleles in healthy older people (55-77 years old). Two saliva samples were collected during the neuropsychological session to obtain cortisol levels and the ApoE genotype. Results showed an association between the ApoE genotype and declarative memory, specifically learning ability, where ApoE-ε2 group performed better than ApoE-ε4 and ApoE-ε3 groups. No differences in cortisol levels were obtained considering the ApoE genotype. In addition, higher mean cortisol levels were related to a worse performance on declarative memory, for the whole sample, and when considering the three allelic variation, for the ApoE-ε4 group. On the contrary, an increase of cortisol levels during the neuropsychological session was associated to a better performance on declarative memory for the whole sample, and for the ApoE-ε3 group when considering the three alleles. Besides, ApoE-ε3 group also showed an association between higher mean cortisol levels and a better attention performance. Therefore, our results suggest that carrying the ApoE-ε4 allele may be a vulnerability factor in the adverse effects of Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation on cognition during aging, while ApoE-ε3 allele could be associated to a more adaptive HPA axis response.
载脂蛋白 E4（ApoE-ε4）等位基因被认为是迟发性阿尔茨海默病（AD）的主要风险因素，而载脂蛋白 E-ε2 等位基因被认为是保护性因素。这些提议增加了人们对健康人群中载脂蛋白基因型影响的兴趣。此外，皮质醇水平升高与认知功能下降有关。然而，很少有研究调查考虑到不同的 ApoE 等位基因，认知表现与皮质醇之间的关系。因此，本研究旨在评估不同的认知领域（陈述性和工作记忆、注意力和执行功能）及其与皮质醇的关系，考虑到健康老年人（55-77 岁）中的 ApoE-ε2、ApoE-ε3 和 ApoE-ε4 等位基因。在神经心理学测试期间采集了两份唾液样本，以获得皮质醇水平和 ApoE 基因型。结果表明，ApoE 基因型与陈述性记忆，特别是学习能力相关，ApoE-ε2 组的表现优于 ApoE-ε4 和 ApoE-ε3 组。考虑到 ApoE 基因型，皮质醇水平没有差异。此外，较高的平均皮质醇水平与整个样本的陈述性记忆表现较差相关，当考虑三个等位基因变异时，与 ApoE-ε4 组相关。相反，整个样本中，神经心理学测试期间皮质醇水平的增加与陈述性记忆的表现更好相关，当考虑三个等位基因时，与 ApoE-ε3 组相关。此外，ApoE-ε3 组还显示出较高的平均皮质醇水平与注意力表现更好之间的相关性。因此，我们的研究结果表明，携带 ApoE-ε4 等位基因可能是下丘脑-垂体-肾上腺（HPA）轴失调对衰老过程中认知产生不利影响的脆弱因素，而 ApoE-ε3 等位基因可能与更适应的 HPA 轴反应相关。
