The Nicotinic Cholinergic System and Cognitive Aging

烟碱胆碱能系统和认知衰老

• 批准号: 9711124
• 负责人: JULIE A DUMAS
• 金额: $ 29.01万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9711124
• 关键词: Activities of Daily Living; Address; Adult; Affect; Age; Aging; Area; Attention; Brain; Clinical Trials; Cognition; Cognitive; Cognitive Science; Cognitive aging; Data; Decision Making; Dementia; Disease; Elderly; Frontal gyrus; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Impaired cognition; Impairment; Institute of Medicine (U.S.); Medial; Memory; Methods; Modeling; Neurobehavioral Manifestations; Neurobiology; Neurons; Neurotransmitters; Nicotinic Antagonists; Nicotinic Receptors; Nootropic Agents; Normal Range; Pattern; Performance; Pharmacology; Placebos; Play; Problem Solving; Public Health; Research; Role; Short-Term Memory; Societies; Structure; System; Task Performances; Testing; Therapeutic; Work; age difference; age effect; age related; age related cognitive change; aging brain; aging population; base; cholinergic; cognitive function; cognitive process; cognitive task; falls; financial decision making; healthy aging; improved; memory encoding; mild cognitive impairment; neurochemistry; neuron loss; non-demented; normal aging; novel; older women; psychological aspect of aging; psychopharmacologic; receptor function; remediation; response; theories; young adult

The cholinergic system has been shown to be the primary neurotransmitter system responsible for cognitive symptoms in dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and the nicotinic system specifically plays in cognition in healthy non-demented older adults (referred to as cognitive aging in this application). This is critical because the expansion of the healthy aging population will nonetheless show declines in cognition that fall short of dementia but still impact functional abilities, independence, and financial decision making. Understanding the effects of age-related functional changes on the nicotinic system will elucidate one neurochemical mechanism underlying age-related changes in cognition and will provide information about how nicotinic dysfunction affects cognition in healthy older adults. Prior research has shown that the nicotinic system has a roll in attention and memory in healthy adults. More recently, with the increased use of brain functional magnetic resonance imaging (fMRI) in combination with psychopharmacological manipulations, data patterns have emerged that further define the role of the nicotinic system in cognition, aging, and dementia. We propose that nicotinic system changes are responsible for age differences in working memory task performance and brain activation. We can observe the functioning of the nicotinic system by examining brain activation patterns in response to nicotinic blockade and stimulation. Increased medial frontal gyrus (MFG) activation has been shown in older adults compared to younger adults. We propose that temporary antagonism of the nicotinic system will model this “older pattern” of impaired performance and increased MFG activation. We hypothesize that older adults will have greater performance impairments and increased MFG activation compared to younger adults after nicotinic blockade. We also propose that nicotinic stimulation will result in “younger patterns” of better performance and decreased MFG activation. We hypothesize that nicotinic stimulation will improve performance and this improvement will be greater for older adults compared to younger adults. We will also observe decreased MFG activation that will be greater for older adults compared to younger adults. These data will further the understanding of one neurochemical mechanism involved in normal aging and how brain activation patterns relate to receptor function. As the search continues for safe and effective cognitive enhancers, it will be important to understand the role of the nicotinic system in cognitive aging and whether nicotinic mechanisms have the potential to benefit cognition in healthy adults.

胆碱能系统已被证明是负责的主要神经递质系统 痴呆症的认知症状。虽然痴呆症的治疗效果是显而易见的，但仍不确定的是 一般胆碱能系统和烟碱系统在健康认知中的具体作用 非痴呆老年人（在本申请中称为认知老化）。这很关键，因为 尽管如此，健康老龄化人口的扩张仍将导致认知能力下降 痴呆症，但仍影响功能能力、独立性和财务决策。了解 与年龄相关的功能变化对烟碱系统的影响将阐明一种神经化学机制 潜在的与年龄相关的认知变化，并将提供有关烟碱功能障碍如何影响的信息 健康老年人的认知能力。先前的研究表明，烟碱系统对注意力和注意力有影响。 健康成年人的记忆力。最近，随着脑功能磁共振的使用增加 成像（fMRI）与精神药理学操作相结合，已经出现的数据模式表明 进一步明确烟碱系统在认知、衰老和痴呆中的作用。 我们认为烟碱系统的变化是工作记忆任务中年龄差异的原因 表现和大脑激活。我们可以通过检查大脑来观察烟碱系统的功能 响应烟碱阻断和刺激的激活模式。额内侧回 (MFG) 增加 与年轻人相比，老年人的激活程度更高。我们建议暂时的对抗 烟碱系统的功能将模拟这种表现受损和 MFG 激活增加的“旧模式”。 我们假设老年人的表现会受到更大的损害，并且 MFG 激活会增加 与烟碱阻断后的年轻人相比。我们还建议烟碱刺激会导致 “更年轻的模式”具有更好的表现和减少的 MFG 激活。我们假设烟碱 刺激会提高表现，并且与老年人相比，这种改善对于老年人来说会更大 年轻的成年人。我们还将观察到 MFG 激活减少，与老年人相比，这种情况会更大 给年轻人。这些数据将进一步了解涉及的一种神经化学机制 正常衰老以及大脑激活模式与受体功能的关系。随着安全搜寻工作的继续进行 和有效的认知增强剂，了解烟碱系统在认知中的作用非常重要 衰老以及烟碱机制是否有可能有益于健康成年人的认知。