Aging-related losses in dopamine D2/3 receptor availability are linked to working-memory decline across five years.

IF 2.9 2区医学 Q2 NEUROSCIENCES Cerebral cortex Pub Date : 2025-02-05 DOI:10.1093/cercor/bhae481

Goran Papenberg, Nina Karalija, Alireza Salami, Jarkko Johansson, Anders Wåhlin, Micael Andersson, Jan Axelsson, Douglas D Garrett, Katrine Riklund, Ulman Lindenberger, Lars Nyberg, Lars Bäckman

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Abstract

Although age differences in the dopamine system have been suggested to contribute to age-related cognitive decline based on cross-sectional data, recent large-scale cross-sectional studies reported only weak evidence for a correlation among aging, dopamine receptor availability, and cognition. Regardless, longitudinal data remain essential to make robust statements about dopamine losses as a basis for cognitive aging. We present correlations between changes in D2/3 dopamine receptor availability and changes in working memory measured over 5 yr in healthy, older adults (n = 128, ages 64 to 68 yr at baseline). Greater decline in D2/3 dopamine receptor availability in working memory-relevant regions (caudate, middle frontal cortex, hippocampus) was related to greater decline in working memory performance in individuals who exhibited working memory reductions across time (n = 43; caudate: rs = 0.494; middle frontal cortex: rs = 0.506; hippocampus; rs = 0.423), but not in individuals who maintained performance (n = 41; caudate: rs = 0.052; middle frontal cortex: rs = 0.198; hippocampus; rs = 0.076). The dopamine-working memory link in decliners was not observed in the orbitofrontal cortex, which does not belong to the core working memory network. Our longitudinal analyses support the notion that aging-related changes in the dopamine system contribute to working memory decline in aging.

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与衰老相关的多巴胺D2/3受体可用性的丧失与五年内工作记忆的下降有关。

尽管基于横断面数据，多巴胺系统的年龄差异被认为是与年龄相关的认知能力下降有关的因素，但最近的大规模横断面研究仅报告了衰老、多巴胺受体可用性和认知能力之间存在相关性的微弱证据。无论如何，纵向数据对于多巴胺损失作为认知衰老的基础的有力陈述仍然是必不可少的。我们提出了健康老年人（n = 128，基线年龄64 - 68岁）在5年内测量的D2/3多巴胺受体可用性变化与工作记忆变化之间的相关性。工作记忆相关区域（尾状、中额叶皮层、海马体）D2/3多巴胺受体可用性的较大下降与工作记忆表现的较大下降有关(n = 43；尾状：rs = 0.494；中额叶皮质：rs = 0.506；海马状突起;Rs = 0.423)，但在保持表现的个体中没有(n = 41；尾状：rs = 0.052；中额叶皮层：rs = 0.198；海马状突起;rs = 0.076)。在眼窝额叶皮层中没有观察到多巴胺与工作记忆的联系，而眼窝额叶皮层不属于核心工作记忆网络。我们的纵向分析支持这样一种观点，即多巴胺系统中与衰老相关的变化导致了衰老过程中工作记忆的下降。

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来源期刊

Cerebral cortex 医学-神经科学

CiteScore

6.30

自引率

8.10%

发文量

510

审稿时长

2 months

期刊介绍： Cerebral Cortex publishes papers on the development, organization, plasticity, and function of the cerebral cortex, including the hippocampus. Studies with clear relevance to the cerebral cortex, such as the thalamocortical relationship or cortico-subcortical interactions, are also included. The journal is multidisciplinary and covers the large variety of modern neurobiological and neuropsychological techniques, including anatomy, biochemistry, molecular neurobiology, electrophysiology, behavior, artificial intelligence, and theoretical modeling. In addition to research articles, special features such as brief reviews, book reviews, and commentaries are included.