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

基本信息

批准号：
10360578
负责人：
Eran Dayan
金额：
$ 38.8万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10360578
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 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 multimodal neuroimaging neuroimaging phenotypic data relating to nervous system resilience trend

项目摘要

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着增加。这种增加转化为与衰老相关的认知能力下降和轻度认知能力的日益普遍损伤（MCI），导致巨大的个人和社会负担。尽管研究兴趣日益浓厚，与衰老相关的认知能力下降的机制仍知之甚少。特别是，它仍然尚不清楚为什么某些人更容易受到认知老化的不利后果的影响，而其他人似乎受到保护，免受同样的影响。可以解释脆弱性的可能机制而抵抗衰老对认知能力下降影响的能力就是冗余。这个设计原则是指系统中存在重复的元素，在发生故障时提供替代功能。尽管系统工程和生物学领域的大量研究都集中在人工和生物中冗余的作用上。有机系统，对冗余作为一种可能的神经保护机制的实证检验迄今为止尚未进行与衰老相关的认知衰退的研究。当前研究的目的是测试功能性和结构性大脑网络的冗余是否可以预防与衰老相关的认知能力下降和轻度认知障碍。为此，我们将分析来自现有大规模数据集的横截面和纵向神经影像和表型数据，其中获得了结构、扩散和功能磁共振成像数据，以及一系列利用认知功能的测试和量表。在该研究的目标 1 中，我们将测试多个年龄组（35 至 85 岁）的大规模功能和结构网络的冗余与认知控制和执行功能测试的表现之间的关联。我们假设，在老年受试者中，冗余将与认知测量方面的优异表现相关。患有 MCI 的老年人也会出现认知能力下降。因此，在目标 2 中，我们将使用横截面神经影像数据来测试 MCI 受试者相对于功能和结构网络中的正常对照是否表现出改变的网络冗余。最后，为了确定冗余是否对认知衰退和 MCI 具有神经保护作用，在目标 3 中，我们将分析纵向神经影像数据，测试认知的纵向变化是否伴随着网络冗余的相应变化，以及网络冗余是否可以预测未来认知的变化。功能。共，该研究旨在确定与衰老相关的认知能力下降是否与结构和功能冗余有关脑基质。为此，本研究旨在提供有关人类衰老和衰老的机制上的重要信息。与衰老相关的认知能力下降的可能原因。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lower functional hippocampal redundancy in mild cognitive impairment.

轻度认知障碍中功能性海马冗余度较低。

DOI：
发表时间：
2021
期刊：
影响因子：
6.8
作者：
Langella, Stephanie;Sadiq, Muhammad Usman;Mucha, Peter J;Giovanello, Kelly S;Dayan, Eran;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative

Accrual of functional redundancy along the lifespan and its effects on cognition.

生命周期中功能冗余的累积及其对认知的影响。

DOI：
发表时间：
2021
期刊：
影响因子：
5.7
作者：
Sadiq, Muhammad Usman;Langella, Stephanie;Giovanello, Kelly S;Mucha, Peter J;Dayan, Eran
通讯作者：
Dayan, Eran

The spatial distribution of coupling between tau and neurodegeneration in amyloid-β positive mild cognitive impairment.

淀粉样蛋白-β 阳性轻度认知障碍中 tau 与神经变性之间耦合的空间分布。

DOI：
发表时间：
2024-04
期刊：
影响因子：
4.2
作者：
Robinson, Belfin;Bhamidi, Shankar;Dayan, Eran;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative

A robust core architecture of functional brain networks supports topological resilience and cognitive performance in middle- and old-aged adults.

功能性大脑网络的强大核心架构支持中老年人的拓扑弹性和认知表现。