Redundancy as a neuroprotective mechanism against aging-related cognitive decline

冗余作为对抗衰老相关认知衰退的神经保护机制

• 批准号: 9912687
• 负责人: Eran Dayan
• 金额: $ 39.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912687
• 关键词: Address; Age; Aging; Biology; Biometry; Brain; Cognition; Cognitive; Cognitive aging; Communities; Cross-Sectional Studies; Data; Data Set; Diffusion; Economic Burden; Elderly; Elements; Engineering; Engineering Psychology; Exhibits; Failure; Family; Functional Magnetic Resonance Imaging; Future; Goals; Healthcare Systems; Human; Impaired cognition; Individual; Individual Differences; Knowledge; Link; Magnetic Resonance Imaging; Mathematics; Measures; Medical Economics; Neurologic Dysfunctions; Neurosciences; Outcome Measure; Pathway Analysis; Patients; Performance; Prevalence; Problem Solving; Public Health; Research; Role; Scanning; Structure; System; Testing; To specify; Translating; United States; adverse outcome; age effect; age group; behavioral outcome; clinical care; cognitive control; cognitive function; cognitive performance; computer science; design; executive function; experience; flexibility; interest; large scale data; mild cognitive impairment; multidisciplinary; multimodality; neuroimaging; phenotypic data; relating to nervous system; resilience; trend

Recent years have seen a significant increase in the proportion of elderly individuals in the United States. This increase is translated to a growing prevalence of aging-related cognitive decline and mild cognitive impairment (MCI), leading to substantial individual and societal burden. Despite increasing research interest, the mechanisms that underlie aging-related cognitive decline remain poorly understood. In particular, it remains unknown why certain individuals are more susceptible to the adverse consequences of cognitive aging, while others appear to be protected from the same effects. A possible mechanism which may explain vulnerability to and resilience against the effects of aging on cognitive decline is redundancy. This design principle refers to the existence of duplicate elements within a system, which provide alternative functionality in case of failure. While numerous studies in systems engineering and biology have focused on the role of redundancy in artificial and organic systems, an empirical examination of redundancy as a possible neuroprotective mechanism against aging-related cognitive decline has not been conducted to date. The objective of the current study is to test if redundancy in functional and structural brain networks protects against aging-related cognitive decline and MCI. To that end, we will analyze cross-sectional and longitudinal neuroimaging and phenotypic data from existing large-scale datasets, where structural, diffusion and functional magnetic resonance imaging data were obtained, together with a battery of tests and scales tapping cognitive function. In Aim 1 of the study we will test the association between redundancy in large-scale functional and structural networks and performance in cognitive control and executive function tests across multiple age groups (ages 35 to 85). We hypothesize that in older subjects, redundancy will be associated with superior performance in measures of cognition. Further along the spectrum of cognitive decline are elderly individuals with MCI. Thus, in Aim 2, we will use cross-sectional neuroimaging data to test if subjects with MCI display altered network redundancy relative to normal controls in functional and structural networks. Finally, to establish if redundancy is neuroprotective against cognitive decline and MCI, in Aim 3 we will analyze longitudinal neuroimaging data, testing whether longitudinal changes in cognition are accompanied by corresponding changes in network redundancy, and whether network redundancy is predictive of future changes in cognitive function. Altogether, the study sets out to determine if aging-related cognitive decline relates to redundancy in structural and functional brain substrates. In doing so, this study aims to offer mechanistically vital information on human aging and the possible causes of aging-related cognitive decline.

近年来，美国老年人的比例显著增加。 这种增加被转化为与年龄相关的认知能力下降和轻度认知能力下降的患病率越来越高。 MCI（英语：MCI），导致个人和社会负担。尽管研究兴趣越来越大， 对与衰老有关的认知能力下降的机制仍然知之甚少。特别是，它仍然 不知道为什么某些人更容易受到认知老化的不良后果，而 其他人似乎受到保护，免受同样的影响。一种可能的机制，可以解释脆弱性， 而抵抗衰老对认知能力下降影响的能力是多余的。这一设计原则是指 系统中存在重复的元素，在出现故障时提供替代功能。而 系统工程和生物学中的许多研究都集中在冗余在人工和 有机系统，冗余作为一种可能的神经保护机制， 迄今尚未进行与年龄相关的认知能力下降的研究。目前研究的目的是测试功能和结构大脑网络中的冗余是否可以防止与衰老相关的认知衰退和MCI。为此，我们将分析现有大规模数据集的横截面和纵向神经成像和表型数据，其中获得了结构，扩散和功能磁共振成像数据，以及一系列测试和量表挖掘认知功能。在本研究的目标1中，我们将测试大规模功能和结构网络中的冗余与多个年龄组（35至85岁）的认知控制和执行功能测试中的表现之间的关联。我们假设，在老年受试者中，冗余将与认知测量中的上级表现相关。此外，沿着认知下降的谱是患有MCI的老年个体。因此，在目标2中，我们将使用横截面神经影像学数据来测试MCI受试者在功能和结构网络中相对于正常对照是否显示出改变的网络冗余。最后，为了确定冗余是否对认知下降和MCI具有神经保护作用，在目标3中，我们将分析纵向神经成像数据，测试认知的纵向变化是否伴随着网络冗余的相应变化，以及网络冗余是否预测未来认知功能的变化。总的来说， 这项研究旨在确定与年龄相关的认知能力下降是否与结构和功能上的冗余有关， 脑基质在这样做的过程中，这项研究的目的是提供有关人类衰老和衰老机制的重要信息。 与衰老相关的认知能力下降的可能原因。