Aging Research Center, Karolinska Institute, Stockholm, Sweden.
Biol Psychiatry. 2010 Mar 15;67(6):575-80. doi: 10.1016/j.biopsych.2009.12.013.
Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity.
We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults.
An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response.
These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.
先前的相关性研究间接表明，多巴胺能神经传递功能障碍与年龄相关的认知缺陷以及与任务相关的功能性大脑活动减少有关。
我们使用实验性药理学功能磁共振成像（fMRI）方法更直接地检查多巴胺在神经认知老化中的作用。纳入了 20 名年轻成年人和 20 名健康老年人。在 fMRI 扫描期间，在两种认知负荷条件下进行空间工作记忆（SWM）任务。使用 D1 受体拮抗剂 [(11)C]SCH23390 的正电子发射断层扫描测量证实，在年轻成年人中，给定的实验剂量未标记溶液占据了 50％的 D1 受体。
观察到 SWM 表现随年龄增长而下降，并且 fMRI 数据显示，与安慰剂条件下的年轻成年人相比，老年人在 SWM 期间对负荷敏感的额顶叶区域的招募减少。关键的是，在年轻成年人中，D1 拮抗剂导致 SWM 表现和 fMRI 反应相似的降低。
这些结果表明，多巴胺的耗竭，无论是先天还是药理学，都会导致 SWM 表现下降以及额顶叶区域血氧水平依赖信号的负荷依赖性调节减少，这可能是通过降低相关神经网络中的信号噪声比。
