Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: = 181, age: 64–68 years; 5-year follow-up: = 129) who underwent positron emission tomography with C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

中文翻译：

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纵向支持衰老、多巴胺 D2 样受体丧失和记忆力衰退之间的相关三联体

多巴胺下降被认为是与衰老相关的认知能力下降的基础，但目前缺乏对这种联系的纵向研究。我们分析了健康老年人样本（基线：= 181，年龄：64-68 岁；5 年随访：= 129）的 5 年纵向数据，这些老年人接受了 C-雷氯必利的正电子发射断层扫描以评估多巴胺D2 样受体 (DRD2) 可用性、用于评估大脑结构测量的磁共振成像以及认知测试。还收集了健康、生活方式和遗传数据。数据驱动的方法（k 均值聚类分析）确定了年龄敏感大脑区域中 DRD2 下降率差异最大的组。一组 (n = 47) 的 DRD2 下降仅发生在尾状核，但认知能力没有下降。第二组（n = 72）在壳核和伏隔核以及纹状体外区域有更广泛的 DRD2 下降。后者表现出显着的 5 年工作记忆下降，与壳核 DRD2 下降相关，同时伴有更高的痴呆和心血管风险以及更快的生物衰老速度。总而言之，对于 DRD2 下降更广泛的个体来说，多巴胺下降与衰老过程中的记忆力下降有关。