Department of Neuroscience, University of California Riverside, Riverside, California, USA.
Department of Psychology, Wayne State University, Detroit, Michigan, USA.
Hum Brain Mapp. 2021 Dec 1;42(17):5761-5770. doi: 10.1002/hbm.25652. Epub 2021 Sep 14.
Evidence from animal and histological studies has indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multicompartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R2*) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate-high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron-related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron-related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron-related gliosis and extend our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.
动物和组织学研究的证据表明，大脑中铁的积累会导致反应性神经胶质增生，从而导致认知缺陷。本研究将这些发现扩展到人类认知衰老，并表明磁共振成像 (MRI) 技术，如定量弛豫率，可以用于研究体内的铁及其作用。使用定量弛豫率和多室扩散成像技术，在 35 名年轻成年人（21.06±2.18 岁）和 28 名老年成年人（72.58±6.47 岁）中，结合定量弛豫率和多室扩散成像技术，研究了铁对微观结构和记忆表现的影响，这些成年人还完成了一项记忆任务。研究结果与过去的研究结果一致，显示出与年龄相关的铁含量（R2*）和扩散增加，以及记忆表现下降。与年龄组无关，铁含量与低-中度铁含量区域（海马体、尾状核）的受限（细胞内）扩散以及中等-高铁含量区域（壳核、苍白球）的所有扩散指标显著相关。这种模式与铁相关神经胶质增生的不同阶段一致，从可能影响细胞内扩散的星形胶质增生到微胶质增殖和增加的血管通透性，可能影响所有扩散源。此外，海马体的受限扩散与记忆表现显著相关，其中三分之一的影响与铁含量有关；这与假设一致，即海马体中铁相关星形胶质增生较高与较差的记忆表现有关。这些结果表明 MRI 对铁相关神经胶质增生具有敏感性，并通过显示这种关系也可以解释记忆表现的个体差异，从而扩展了我们对其对认知影响的理解。
