Non-heme iron accumulation contributes to age-related decline in brain structure and cognition via a cascade of oxidative stress and inflammation, although its effect on brain function is largely unexplored. Thus, we examine the impact of striatal iron on dynamic range of BOLD modulation to working memory load. N = 166 healthy adults (age 20-94) underwent cognitive testing and an imaging session including n-back (0-, 2-, 3-, and 4-back fMRI), R2*-weighted imaging, and pcASL to measure cerebral blood flow. A statistical model was constructed to predict voxelwise BOLD modulation by age, striatal iron content and an age × iron interaction, controlling for cerebral blood flow, sex, and task response time. A significant interaction between age and striatal iron content on BOLD modulation was found selectively in the putamen, caudate, and inferior frontal gyrus. Greater iron was associated with reduced modulation to difficulty, particularly in middle-aged and younger adults with greater iron content. Further, iron-related decreases in modulation were associated with poorer executive function in an age-dependent manner. These results suggest that iron may contribute to differences in functional brain activation prior to older adulthood, highlighting the potential role of iron as an early factor contributing to trajectories of functional brain aging.

中文翻译：

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纹状体铁含量与工作记忆负荷下的额叶纹状体脑功能降低有关

非血红素铁积累通过氧化应激和炎症的级联反应导致与年龄相关的大脑结构和认知能力下降，尽管其对大脑功能的影响在很大程度上尚未得到探索。因此，我们研究了纹状体铁对 BOLD 调制对工作记忆负荷的动态范围的影响。N = 166 名健康成年人（20-94 岁）接受了认知测试和成像会话，包括 n-back（0-、2-、3-和 4-back fMRI）、R2*-加权成像和 pcASL 以测量大脑血流量。构建了一个统计模型来预测年龄、纹状体铁含量和年龄 × 铁相互作用的体素 BOLD 调制，控制脑血流量、性别和任务响应时间。年龄和纹状体铁含量对 BOLD 调制的显着相互作用在壳核、尾状核、和额下回。更多的铁与减少对困难的调节有关，特别是在铁含量更高的中年和年轻人中。此外，与铁相关的调制减少与年龄相关的执行功能较差有关。这些结果表明，铁可能导致成年之前功能性大脑激活的差异，突出了铁作为促成功能性大脑衰老轨迹的早期因素的潜在作用。