Sinclair Lindsey I, Button Katherine S, Munafò Marcus R, Day Ian N M, Lewis Glyn
School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, United Kingdom; UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, United Kingdom.
PLoS One. 2015 Aug 19;10(8):e0135894. doi: 10.1371/journal.pone.0135894. eCollection 2015.
Possession of the ε4 allele of the Apolipoprotein E (APOE) gene is associated with an increased risk of Alzheimer's disease. Early adult life effects of ε4 are less well understood. Working memory has been relatively little studied (compared to episodic memory) in relation to APOE genotype despite its importance in cognitive functioning. Our hypothesis was that ε4 would lead to an impairment in working memory in young adults.
We studied working memory using a computerised n-back task in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18. Data was available for 1049-1927 participants and for the 2- and 3-back versions of the task. Using multiple and multi-level regression controlling for important confounders we examined the association between APOE genotype on accuracy and reaction times.
There was no evidence of a genotype effect on accuracy when the two difficulty levels were examined separately. There was some evidence to support a deleterious effect of the ε4 allele on n-back accuracy in the multi-level regression. There was weak evidence that the ε22 group were less accurate but the numbers were very low in this group. The ε34 group had faster reaction times than the reference ε33 group in all adjusted analyses but the ε44 group were only faster in the 3-back condition in multi-level analyses.
There was no evidence of benefit in ε4 carriers, but there was some evidence of a detrimental effect on working memory in this large study.
载脂蛋白E(APOE)基因的ε4等位基因与阿尔茨海默病风险增加有关。ε4在成年早期的影响尚不太清楚。尽管工作记忆在认知功能中很重要,但与APOE基因型相关的工作记忆研究(与情景记忆相比)相对较少。我们的假设是,ε4会导致年轻人工作记忆受损。
我们在雅芳亲子纵向研究(ALSPAC)中,使用计算机化的n-back任务对18岁的参与者进行工作记忆研究。有1049 - 1927名参与者的数据,以及该任务的2-back和3-back版本的数据。我们使用多因素和多层次回归控制重要混杂因素,研究APOE基因型与准确性和反应时间之间的关联。
分别检查两个难度水平时,没有证据表明基因型对准确性有影响。在多层次回归中,有一些证据支持ε4等位基因对n-back准确性有有害影响。有微弱证据表明ε22组的准确性较低,但该组人数很少。在所有调整分析中,ε34组的反应时间比参照ε33组快,但在多层次分析中,ε44组仅在3-back条件下反应更快。
在这项大型研究中,没有证据表明ε4携带者有获益,但有一些证据表明对工作记忆有不利影响。