Quantitative Susceptibility Mapping of Iron Accumulation in Neurocognitive Aging

深部灰质(DGM)区的铁浓度与神经退行性变有关 在没有疾病的情况下，DGM铁也会随着成年年龄的增长而增加。上一首 已有研究报道，与年龄相关的DGM铁蓄积与 神经认知功能的某些方面。然而，以前的研究通常集中在一个 神经认知结果测量的数量有限，通常偏向于运动功能， 并依赖于不太理想的核磁共振方法来估计铁的浓度，例如核磁共振 松弛测量法。此外，尽管结构性和功能性大脑连接性的下降似乎 导致健康衰老的神经认知功能下降，铁在这种下降中的作用尚不清楚。 在这个项目中，我们测试了一个与年龄相关的DGM铁积累对 神经认知功能，提出与年龄相关的DGM铁有助于氧化应激和 从而导致网络连通性下降。这项研究将调查 DGM铁的定量磁化率作图(QSM)--一种新的有效技术 这比以前估计转基因铁的方法(例如，弛豫法)有几个优点。 这项研究包括270名健康社区居民的成像和神经认知测试 个人，每个人年龄在60岁：20岁、30岁、40岁、50岁、60岁和70岁。 60多岁和70多岁的参与者将在两个时间点进行测试，大约3年 分开。目标1将检验这一假设，即尾状体头中的铁将具有更大的 对年龄与神经认知之间关系的中介或调节影响 这一影响将扩大到以下措施： 决策过程的效率(漂移率)。目标2将检验与年龄相关的假设 DGM铁的增加，特别是在尾状体头，影响结构和 以连续方式进行功能连接，并在DGM铁之间建立区域特定的关联， 额纹状体回路的白质(WM)完整性，以及大脑皮质的功能连通性 关联休眠状态网络(RSN)。目标3将检验与年龄相关的假设 在横断面分析中，可以确认目标1和目标2中确定的DGM铁的影响 纵向来看，时间间隔为三年。因此，该项目将有助于 比目前可用的更全面的理论模型，DGM铁对 年龄与神经认知功能的关系。这些发现还将与以下方面相关 评估DGM铁作为神经退行性疾病生物标记物的潜在作用。

Iron concentration in deep gray matter (DGM) regions is associated with neurodegenerative disease, but DGM iron also increases with adult age, in the absence of disease. Previous studies have reported association between age-related DGM iron accumulation and decline in some aspects of neurocognitive function. However, previous studies have typically focused on a limited number of neurocognitive outcome measures, often biased towards motor functioning, and have relied on less than optimal MRI methods to estimate iron concentration, such as MRI relaxometry. Further, although decline in structural and functional brain connectivity appears to contribute to neurocognitive decline in healthy aging, the role of iron in this decline is not clear. In this project we test a model of the influence of age-related DGM iron accumulation on neurocognitive function, proposing that age-related DGM iron contributes to oxidative stress and consequently to a decline in network connectivity. The research will investigate the effects of DGM iron using Quantitative Susceptibility Mapping (QSM), a novel and validated technique that has several advantages over previous methods for estimating GM iron (e.g., relaxometry). This research comprises imaging and neurocognitive testing of 270 healthy, community-dwelling individuals, with 45 individuals in each of six age decades: 20s, 30s, 40s, 50s, 60s, and 70s. The participants in their 60s and 70s will be tested at two time points, approximately 3 years apart. Aim 1 will test the hypothesis that iron in the head of the caudate will have a greater mediating or moderating influence, on the relation between age and the neurocognitive measures, relative to other DGM regions, and that this influence will extend to measures of the efficiency of decision processes (drift rate). Aim 2 will test the hypothesis that age-related increase in DGM iron, particularly in the head of the caudate, influences structural and functional connectivity in a serial manner, with regionally specific associations among DGM iron, the white matter (WM) integrity of frontostriatal circuits, and the functional connectivity of associated resting-state networks (RSNs). Aim 3 will test the hypothesis that the age-related influences of DGM iron identified in Aims 1 and 2, in cross-sectional analyses, can be confirmed longitudinally, across a three-year interval. The project will consequently contribute to a more comprehensive theoretical model, than presently available, of the influence of DGM iron on the relation between age and neurocognitive performance. The findings will also be relevant to assessing the potential role of DGM iron as a biomarker of neurodegenerative disease.