Measuring Cognitive Fatigability in Older Adults

描述（由申请人提供）：疲劳与老年人死亡率增加有关，是该人群活动受限的主要原因。不幸的是，我们对老年人疲劳的原因的了解相当有限，我们没有经过验证的治疗方法。虽然我们知道衰老对中枢神经系统（CNS）和认知功能有深远的影响，但迄今为止还没有研究试图了解中枢神经系统和认知因素如何导致老年人的疲劳抱怨和活动限制。这是一个惊人的差距，因为中枢神经系统和认知因素可能在许多被怀疑导致老年人疲劳的过程中发挥核心作用，因此将成为治疗干预的有力目标。疲劳是一个复杂的概念，它包括主观感知（感知疲劳）和客观表现变化（疲劳）。本研究的目的是：1)确定老年人认知表现疲劳的客观测量与活动水平之间的关系；2)确定这种疲劳的潜在神经机制。长期目标是确定针对认知和/或中枢神经系统目标的干预措施是否能恢复受疲劳折磨的老年人的活动水平。核心假设是，老年人的认知表现疲劳会导致活动受限，这是由于与衰老相关的神经认知变化。这一假设是基于我们的初步数据得出的：1)老年人的认知疲劳与年龄和疲劳主诉之间存在显著相关性；2)认知储备生理指标与认知疲劳的关系。提出这项研究的基本原理是，需要更好地客观测量认知和中枢神经系统因素，以提高我们对老年人疲劳的理解，并确定治疗干预的目标。该假设将通过两个具体目标进行检验：1)确定老年人认知表现疲劳与活动水平之间的相关性；2)利用脑电图（EEG）确定认知疲劳与认知储备神经生理指标的关系。该方法具有创新性，因为它代表了第一个将客观认知疲劳作为老年人活动受限原因的研究，也是第一个确定大脑储备的生理测量是否影响认知疲劳的研究。这项研究具有重要意义，因为它有望推进我们对老年人疲劳机制的理解，并为推进这一领域提供新的工具、机制见解和治疗靶点。本R21提案中开发的知识和技术将为未来的R01提案奠定基础，以研究认知干预措施改善老年人活动限制的潜力，并进行机制研究，以更好地了解老年人活动限制的潜在原因，包括认知、中枢神经系统、肌肉、心血管和代谢因素之间的关系和相互作用。

DESCRIPTION (provided by applicant): Fatigue is associated with increased mortality in older adults and is the leading cause of activity restrictions in this population. Unfortunately, our understanding of the causes of fatigue in older adults is quite limited and we have no proven treatments. While it is known that aging has profound effects on the central nervous system (CNS) and cognitive function there have been no studies to date attempting to understand how CNS and cognitive factors contribute to fatigue complaints and activity restrictions in older adults. This is a striking gap as CNS and cognitive factors may play a central role in many processes suspected to drive fatigue in older adults and would thus be a potent target for therapeutic interventions. Fatigue is a complex construct which includes subjective perceptions (perceived fatigue) and objective changes in performance (fatigability). The research objectives of this proposal are to: 1) Determine the association between an objective measure of cognitive performance fatigability and activity levels in older adults; and 2) Identify potential neuronal mechanisms of this fatigability. The long-term goal is to determine whether interventions directed at cognition and/or CNS targets restore activity levels in older adults afflicted by fatige. The central hypothesis is that cognitive performance fatigability in older adults contributes to activity restrictions and is due to aging related neurocognitive changes. This hypothesis has been formulated on the basis of our preliminary data showing: 1) Significant correlations between cognitive fatigability and both age and fatigue complaints in older adults; and 2) Associations between physiologic markers of cognitive reserve and cognitive fatigability. The rationale for the proposed research is that better objective measures of cognitive and CNS factors are needed to advance our understanding of fatigability in older adults and to identify targets for therapeutic interventions. The hypothesis will be tested through two Specific Aims: 1) Determine the correlation between cognitive performance fatigability and activity levels in older adults; and 2) Determine the relationship between cognitive fatigability and neurophysiological markers of cognitive reserve using electroencephalography (EEG). The approach is innovative because it represents the first study to examine objective cognitive fatigability as a cause of restricted activity in older adults and is the first study to determine whether physiologic measures of cerebral reserve impact cognitive fatigability. The proposed research is significant because it is expected to advance out understanding of the mechanisms of fatigability in older adults and to contribute new tools, mechanistic insights and therapeutic targets essential for advancing this field. The knowledge and techniques developed in this R21 proposal will serve as a foundation for future R01 proposals to investigate the potential for cognitive interventions t improve activity restrictions in older adults and mechanistic studies to better understand the relationship and interaction of potential causes of restricted activity in older adults including cognitive, CNS, muscular, cardiovascular and metabolic factors.