The contribution of declines in functional connectivity to cognitive aging

功能连接下降对认知衰老的影响

• 批准号: 9197589
• 负责人: SARA N BURKE
• 金额: $ 37.91万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197589
• 关键词: Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; American; Anatomy; Animal Model; Animals; Area; Behavior; Behavioral; Brain; Brain region; Cells; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Communication; Data; Data Set; Development; Disease; Elderly; Engineering; Evaluation; Financial compensation; Functional Imaging; Functional disorder; Future; Goals; Hippocampus (Brain); Human; Image; Immediate-Early Genes; Impaired cognition; Impairment; Individual; Interdisciplinary Study; Intervention; Intervention Studies; Label; Lateral; Link; Long-Term Care; Measures; Medial; Mediating; Memory; Memory Loss; Memory impairment; Messenger RNA; Methodology; Methods; Mission; Nature; Nerve Degeneration; Neurobiology; Neurons; Outcome; Pathology; Performance; Positioning Attribute; Pre-Clinical Model; Prefrontal Cortex; Process; Public Health; Quality of life; Rattus; Recruitment Activity; Research; Research Personnel; Rodent Model; Sensory; Series; Source; Stimulus; Structure; System; Techniques; Temporal Lobe; Testing; Tracer; Treatment Efficacy; age related; aged; aging brain; base; behavior measurement; cellular imaging; entorhinal cortex; experience; experimental study; improved; in vivo; innovation; juvenile animal; memory process; neuronal excitability; neurophysiology; novel; prefrontal lobe; public health relevance; relating to nervous system; restoration; signal processing; therapy development

 DESCRIPTION (provided by applicant): By the year 2020 the number of Americans over the age of 65 is projected to reach 55 million. It is therefore imperative that the ability of these individuals to live independently is preserved for reasons of personal dignity as well as the financial and public-health consequences that result from the necessity of long-term care. Unfortunately, a large proportion of elderly people experience memory decline that interferes with their quality of life. Understanding the neurobiology of memory impairments in advanced age, however, presents a significant problem, as memory processes are distributed throughout the brain and a fundamental gap exists in our understanding of how these structures interact. The long-term goal of the proposed research is to determine the alterations in network-level interactions that underlie cognitive impairment in advanced age. The primary objective of the current proposal is to identify age-associated changes in medial temporal lobe-prefrontal functional connectivity that contributes to memory deficits. State-of-the-art methodologies in neurophysiology, anatomy and behavioral analysis will be integrated to test the central hypothesis that age-related memory impairments manifest from dysfunction in cross-regional interactions among prefrontal and medial temporal lobe circuits by pursuing the following specific aims: 1) Do deficits in cortical functional connectivity mediate memory impairments, 2) Does age-related perirhinal dysfunction impact activity dynamics within the hippocampus, and 3) Do age-related reductions in prefrontal cortical activity impact functional connectivity in the rhinal cortices. Our rationale is that by elucidating how aging influences systems-level dynamics, we will be better positioned to develop interventions that broadly improve cognition. The proposed research is innovative, because state-of-the-art neuroanatomical measures and neurophysiological techniques will be integrated with measures of behavioral deficits in young and aged rats in order to probe how local dysfunction manifests as network impairments or elicits compensatory mechanisms. The significance of successful completion of these experiments will be to provide an unprecedented understanding of the association between functional connectivity and cognition that will enable future interventional studies aimed at restoring memory network interactions in the context of aging and neurodegeneration.

 描述（由申请人提供）：到 2020 年，美国 65 岁以上的人数预计将达到 5500 万。因此，出于个人尊严以及长期护理的必要性所造成的财务和公共卫生后果，必须保留这些人独立生活的能力。不幸的是，很大一部分老年人的记忆力下降，影响了他们的生活质量。然而，了解老年记忆障碍的神经生物学提出了一个重大问题，因为记忆过程分布在整个大脑中，而我们对这些结构如何相互作用的理解存在根本差距。拟议研究的长期目标是确定导致高龄认知障碍的网络水平交互的改变。当前提案的主要目标是确定导致记忆缺陷的内侧颞叶-前额叶功能连接的与年龄相关的变化。将整合神经生理学、解剖学和行为分析中最先进的方法来测试这一中心假设，即与年龄相关的记忆障碍是由前额叶和内侧颞叶回路之间的跨区域相互作用功能障碍所体现，通过追求以下具体目标：1）皮质功能连接的缺陷是否会介导记忆障碍，2）与年龄相关的鼻周神经元是否会介导记忆障碍？ 功能障碍影响海马体内的活动动态，3）与年龄相关的前额皮质活动减少是否会影响鼻皮质的功能连接。我们的理由是，通过阐明衰老如何影响系统级动态，我们将能够更好地开发广泛改善认知的干预措施。拟议的研究具有创新性，因为最先进的神经解剖学测量和神经生理学技术将与年轻和老年大鼠的行为缺陷测量相结合，以探讨局部功能障碍如何表现为网络损伤或引发补偿机制。成功完成这些实验的意义在于提供对功能连接和认知之间关联的前所未有的理解，这将使未来旨在恢复衰老和神经退行性疾病背景下的记忆网络相互作用的干预研究成为可能。