Elevated Dopamine Synthesis as a Mechanism of Cognitive Resilience in Aging
Elevated Dopamine Synthesis as a Mechanism of Cognitive Resilience in Aging
复制标题
DOI：
10.1093/cercor/bhab379
复制
发表时间：
2021-10-27
期刊：
影响因子：
3.7
通讯作者：
Berry, Anne S.
中科院分区：
文献类型：
--
作者：
Ciampa, Claire J.;Parent, Jourdan H.;Berry, Anne S.
衰老与多巴胺系统的多种成分的减少有关，包括产生多巴胺的神经元的丧失，多巴胺系统的皮质靶点的萎缩，以及多巴胺受体密度的降低。与这些模式相反，多巴胺的合成在老年时似乎是稳定的或升高的。我们测试了这一假设，即老化时多巴胺合成的增加反映了对神经元丢失的代偿性反应，而不是老年时的非特异性单调变化。我们使用[F-18]氟-L-m-酪氨酸正电子发射断层扫描横断面测量了认知正常的老年人纹状体多巴胺合成能力的个体差异，并测试了与13年前开始的皮质厚度纵向减少和工作记忆下降的关系。与补偿解释一致的是，具有最高多巴胺合成能力的老年人是那些顶叶后皮质萎缩最严重的人。多巴胺合成能力的提高与成功维持整体工作记忆表现无关，但具有缓和作用，即较高水平的多巴胺合成能力可以减少萎缩对认知能力下降的影响。总之，这些发现支持了一个模型，通过该模型，多巴胺合成的上调代表了衰老过程中认知弹性的一种机制。
Aging is associated with declines in multiple components of the dopamine system including loss of dopamine-producing neurons, atrophy of the dopamine system's cortical targets, and reductions in the density of dopamine receptors. Countering these patterns, dopamine synthesis appears to be stable or elevated in older age. We tested the hypothesis that elevation in dopamine synthesis in aging reflects a compensatory response to neuronal loss rather than a nonspecific monotonic shift in older age. We measured individual differences in striatal dopamine synthesis capacity in cognitively normal older adults using [F-18]Fluoro-l-m-tyrosine positron emission tomography cross-sectionally and tested relationships with longitudinal reductions in cortical thickness and working memory decline beginning up to 13 years earlier. Consistent with a compensation account, older adults with the highest dopamine synthesis capacity were those with greatest atrophy in posterior parietal cortex. Elevated dopamine synthesis capacity was not associated with successful maintenance of working memory performance overall, but had a moderating effect such that higher levels of dopamine synthesis capacity reduced the impact of atrophy on cognitive decline. Together, these findings support a model by which upregulation of dopamine synthesis represents a mechanism of cognitive resilience in aging.