Xiang Qingyan, Andersen Stacy Lynn, Perls Thomas T, Sebastiani Paola
Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
Section of Geriatrics, Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
Front Genet. 2021 Jan 8;11:606831. doi: 10.3389/fgene.2020.606831. eCollection 2020.
Apolipoprotein E () is an important risk factor for cognitive decline and Alzheimer's disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer's and dementia, while the e2 allele has a positive effect on longevity, and possibly on preservation of cognitive function. Education also has an important effect on cognition and longevity but the interplay between and education is not well-characterized. Previous studies of the effect of on cognitive decline often used linear regression with the normality assumption, which may not be appropriate for analyzing bounded and skewed neuropsychological test scores. In this paper, we applied Bayesian beta regression to assess the effect of alleles on cognitive decline in a cohort of centenarians with longitudinal assessment of their cognitive function. The analysis confirmed the negative association between older age and cognition and the beneficial effect of education that persists even at the extreme of human lifespan in carriers of the e3 allele. In addition, the analysis showed an association between and cognition that is modified by education. Surprisingly, an antagonistic interaction existed between higher education and alleles, suggesting that education may reduce the positive effect of e2 and increase the negative effect of e4 at extreme old age.
载脂蛋白E（）是老年人认知功能衰退和患阿尔茨海默病的一个重要风险因素。在该基因已知的3个等位基因：e2、e3和e4中，e4等位基因与更快的认知衰退以及患阿尔茨海默病和痴呆症的风险增加有关，而e2等位基因对长寿有积极影响，可能对认知功能的保留也有积极影响。教育对认知和长寿也有重要影响，但载脂蛋白E与教育之间的相互作用尚未得到充分描述。以往关于载脂蛋白E对认知衰退影响的研究通常使用具有正态性假设的线性回归，这可能不适用于分析有界且呈偏态分布的神经心理学测试分数。在本文中，我们应用贝叶斯β回归来评估载脂蛋白E等位基因对一组百岁老人认知衰退的影响，这些百岁老人的认知功能经过了纵向评估。分析证实了老年与认知之间的负相关以及教育的有益作用，这种作用在e3等位基因携带者中即使在人类寿命的极限阶段也依然存在。此外，分析表明载脂蛋白E与认知之间的关联受到教育的影响。令人惊讶的是，高等教育与载脂蛋白E等位基因之间存在拮抗相互作用，这表明在极高龄时，教育可能会降低载脂蛋白E e2的积极作用，并增加载脂蛋白E e4的消极作用。
