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: 9028905
• 负责人: SARA N BURKE
• 金额: $ 38.37万
• 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/9028905
• 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 disorder; Future; Goals; Hippocampus (Brain); Human; Image; Immediate-Early Genes; Impaired cognition; Impairment; Individual; Interdisciplinary Study; Intervention; Label; Lateral; Life; 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; 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; Therapeutic; Tracer; age related; aged; aging brain; base; behavior measurement; cellular imaging; entorhinal cortex; experience; improved; in vivo; innovation; juvenile animal; meetings; memory process; neuronal excitability; neurophysiology; novel; pre-clinical; public health relevance; relating to nervous system; research study; 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，65岁以上的美国人预计将达到5500万。因此，出于个人尊严以及长期护理的必要性所造成的经济和公共卫生后果的原因，必须保护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，理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，我们对这些结构如何相互作用的理解存在根本性的差距。拟议研究的长期目标是确定网络水平交互的变化，这些变化是老年认知障碍的基础。目前的建议的主要目标是确定与年龄相关的内侧颞叶-前额叶功能连接的变化，有助于记忆缺陷。将整合神经生理学，解剖学和行为分析的最先进方法，以测试中心假设，即年龄相关的记忆障碍表现为前额叶和内侧颞叶回路之间跨区域相互作用的功能障碍，具体目标如下：1）皮质功能连接缺陷是否介导记忆障碍，2）年龄相关的嗅周功能障碍是否影响海马内的活动动力学？3）与年龄相关的前额叶皮质活动减少是否影响鼻皮质的功能连接。我们的基本原理是，通过阐明衰老如何影响系统水平的动态，我们将更好地开发广泛改善认知的干预措施。拟议的研究是创新的，因为最先进的神经解剖学措施和神经生理学技术将与年轻和老年大鼠的行为缺陷的措施相结合，以探讨局部功能障碍如何表现为网络损伤或兴奋性代偿机制。成功完成这些实验的意义将是对功能连接和认知之间的关联提供前所未有的理解，这将使未来的干预性研究能够在衰老和神经退行性变的背景下恢复记忆网络的相互作用。