Leiden University, Cognitive Psychology Unit & Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Neuropsychologia. 2013 Jun;51(7):1377-81. doi: 10.1016/j.neuropsychologia.2013.01.014. Epub 2013 Jan 29.
Healthy aging beyond the age of 65 is characterized by a general decrease in cognitive control over actions: old adults have more difficulty than young adults in stopping overt responses. Responsible for this cognitive decrement is the continuous decline of striatal and extrastriatal dopamine (DA). The resource-modulation hypothesis assumes that genetic variability is more likely to result in performance differences when brain resources move away from close-to-optimal levels, as in aging. To test this hypothesis we investigated, first, whether individual differences in the C957T polymorphism at DRD2 gene (rs6277) contribute to individual differences in the proficiency to inhibit behavioral responses in a stop-signal task. Second, we assessed whether this genetic effect is magnified in older adults, due to the considerable decline in dopamine function. Our findings show that individuals carrying genotype associated with higher density of extrastriatal D2 receptors (C957T CC) were more efficient in inhibiting unwanted action tendencies, but not in term of response execution. This effect was stronger in older than in younger adults. Our findings support the idea that aging-related decline in dopamine availability alters the balance between genotypes and cognitive functions.
65 岁以上的健康老龄化的特点是认知控制行动的普遍下降:老年人比年轻人更难停止明显的反应。导致这种认知衰退的原因是纹状体和纹状体外多巴胺(DA)的持续下降。资源调节假说假设,当大脑资源偏离接近最佳水平时,例如在衰老过程中,遗传变异更有可能导致表现差异。为了检验这一假设,我们首先调查了 DRD2 基因(rs6277)的 C957T 多态性个体差异是否导致停止信号任务中抑制行为反应能力的个体差异。其次,我们评估了由于多巴胺功能的显著下降,这种遗传效应是否在老年人中放大。我们的研究结果表明,携带与更高密度的纹状体外 D2 受体相关的基因型(C957T CC)的个体在抑制不必要的动作倾向方面更有效,但在反应执行方面则不然。这种效应在老年人中比在年轻人中更强。我们的研究结果支持这样一种观点,即与衰老相关的多巴胺可用性下降改变了基因型和认知功能之间的平衡。