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，也是导致这一人群活动受限的主要原因。不幸的是，我们对老年人疲劳原因的了解相当有限，我们也没有经过验证的治疗方法。虽然众所周知，衰老对中枢神经系统(CNS)和认知功能有深远的影响，但到目前为止，还没有研究试图了解中枢神经系统和认知因素是如何导致老年人疲劳和活动受限的。这是一个显着的差距，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靶点。疲劳是一个复杂的概念，它包括主观感觉(感知疲劳)和客观表现变化(疲劳性)。这项建议的研究目标是：1)确定老年人认知能力疲劳性的客观衡量标准与活动水平之间的联系；2)确定这种疲劳性的潜在神经机制。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困扰的老年人的活动水平。中心假设是，老年人的认知能力疲劳性导致活动受限，并归因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提出的，这些数据表明：1)老年人的认知疲劳性与年龄和疲劳主诉之间存在显著相关性；2)认知储备的生理标志与认知疲劳性之间存在关联。提出这项研究的理由是，需要对认知和中枢神经系统因素进行更好的客观测量，以促进我们对老年人疲劳性的理解，并确定治疗干预的目标。这一假说将通过两个具体的目标来验证：1)确定老年人认知表现疲劳性和活动水平之间的相关性；2)使用脑电(EEG)确定认知疲劳性与认知储备的神经生理标记物之间的关系。这种方法是创新的，因为它是第一项研究客观认知疲劳性是老年人活动受限的原因，也是第一项确定大脑储备的生理指标是否会影响认知疲劳性的研究。这项拟议的研究具有重要意义，因为它有望促进对老年人疲劳机制的理解，并为促进这一领域的发展提供新的工具、机械性见解和治疗靶点。R21提案中开发的知识和技术将作为未来R01提案的基础，以调查认知干预改善老年人活动限制的可能性，以及更好地了解老年人活动受限的潜在原因(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的机制研究。

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.