Institute of Gerontology, Wayne State University, 87 E. Ferry St., Detroit, MI 48202, USA.
Neurobiol Aging. 2011 Jun;32(6):1124-37. doi: 10.1016/j.neurobiolaging.2009.05.015. Epub 2009 Jun 25.
Executive functions (EF) evidence significant age-related declines, but the mechanisms underpinning those changes are unclear. In this study, we focus on two potential sources of variation: a physiological indicator of vascular health, and genetic variants related to vascular functions. In a sample of healthy adults (n=158, ages 18-81), we examine the effects of age, pulse pressure, and two polymorphisms (comt val158met and ace insertion/deletion) on working memory and cognitive flexibility. Results indicate that in addition to often-replicated age differences, the alleles of two polymorphisms that promote vasoconstriction (comt val and ace D) and reduced availability of dopamine in neocortical synapses (comt val), negatively impact virtually all aspects of EF tasks that involve working memory. In some cases, suppression of cognitive performance is limited to men or necessitates a combination of both risk-associated alleles. After accounting for genetic and age-related variation, pulse pressure had no additional effect on EF. These findings suggest that in healthy adults, the effects of genetic risk factors significantly modulate the course of cognitive aging.
执行功能（EF）随着年龄的增长而显著下降，但支持这些变化的机制尚不清楚。在这项研究中，我们关注两个潜在的变异来源：血管健康的生理指标，以及与血管功能相关的基因变异。在一个健康成年人样本（n=158，年龄 18-81 岁）中，我们研究了年龄、脉压和两种多态性（COMT val158met 和 ACE 插入/缺失）对工作记忆和认知灵活性的影响。结果表明，除了经常复制的年龄差异外，两种促进血管收缩（COMT val 和 ACE D）和减少新皮质突触中多巴胺可用性的多态性等位基因（COMT val）也会对涉及工作记忆的 EF 任务的几乎所有方面产生负面影响。在某些情况下，认知表现的抑制仅限于男性，或者需要两种风险相关等位基因的结合。在考虑遗传和年龄相关的变异后，脉压对 EF 没有额外的影响。这些发现表明，在健康成年人中，遗传风险因素的影响显著调节认知衰老的过程。
