Quantitative Susceptibility Mapping of Iron Accumulation in Neurocognitive Aging

神经认知衰老中铁积累的定量敏感性图

• 批准号: 9566397
• 负责人: NAN-KUEI CHEN
• 金额: $ 60.2万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9566397
• 关键词: Adult; Age; Age-associated memory impairment; Aging; Biological Markers; Brain; Cognition; Cognitive; Communities; Cross-Sectional Studies; Data; Development; Diagnosis; Disease; Dorsal; Exhibits; Future; Globus Pallidus; Goals; Head; Human; Image; Individual; Individual Differences; Iron; Laboratories; Linear Regressions; Link; Liquid substance; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mediating; Mediation; Memory; Methods; Modeling; Morphologic artifacts; Motor; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Outcome Measure; Oxidative Stress; Participant; Performance; Predisposition; Procedures; Process; Psychometrics; Public Health; Pulvinar structure; Reaction Time; Red nucleus structure; Reporting; Research; Resistance; Rest; Role; Speed; Structure; Substantia nigra structure; Task Performances; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Theoretical model; Time; age related; analytical method; base; caudate nucleus; executive function; gray matter; healthy aging; improved; information processing; interest; longitudinal analysis; neurocognitive test; normal aging; novel; putamen; theories; virtual; white matter

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.

深灰质（DGM）区域的铁浓度与神经退行性疾病相关。 疾病，但DGM铁也随着成年年龄增加，在没有疾病的情况下。先前 研究已经报道了与年龄相关的DGM铁积累和 神经认知功能的一些方面。然而，以前的研究通常集中在一个 有限数量的神经认知结果测量，通常偏向于运动功能， 并且依赖不太理想的MRI方法来估计铁浓度，例如MRI 弛豫测量法此外，尽管结构和功能性大脑连接的下降似乎 在健康老龄化的神经认知能力下降，铁在这种下降中的作用尚不清楚。 在这个项目中，我们测试了与年龄相关的DGM铁积累的影响模型， 神经认知功能，提出与年龄相关的DGM铁有助于氧化应激， 从而导致网络连通性下降。这项研究将调查的影响， 使用定量易感性映射（QSM）的DGM铁，这是一种新的经验证的技术 其与先前用于估计GM铁的方法相比具有几个优点（例如，弛豫测定法）。 这项研究包括对270名健康的社区居民进行成像和神经认知测试。 个体，在六个年龄段中每个年龄段有45个个体：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 apart.目的1将检验尾状核头部的铁将具有更大的 中介或调节影响，对年龄和神经认知之间的关系， 措施，相对于其他DGM地区，这种影响将扩展到 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，特别是在尾状核的头部，影响结构和 以串联方式的功能连接性，在DGM铁之间具有区域特异性关联， 额纹回路的白色物质（WM）完整性以及功能连接性 关联的休眠状态网络（RSN）。目标3将检验与年龄相关的假设， 在横截面分析中，可以确认目标1和2中确定的DGM铁的影响 纵向地，跨越三年的间隔。因此，该项目将有助于 全面的理论模型，比目前可用的，DGM铁的影响， 年龄与神经认知能力的关系。调查结果还将与以下方面有关： 评估DGM铁作为神经退行性疾病的生物标志物的潜在作用。