The Nicotinic Cholinergic System and Cognitive Aging

烟碱胆碱能系统和认知衰老

基本信息

批准号：
9273350
负责人：
JULIE A DUMAS
金额：
$ 37.51万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
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/9273350
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 Nicotine 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 public health relevance receptor function remediation response theories young adult

项目摘要

DESCRIPTION (provided by applicant): 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 becaus 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.

描述（由申请人提供）：胆碱能系统已被证明是导致痴呆症认知症状的主要神经递质系统，虽然对痴呆症的治疗益处是明确的，但仍不确定胆碱能系统的作用。一般而言，烟碱系统和烟碱系统在健康非痴呆老年人的认知中发挥着特殊作用（在本申请中称为认知老化），这是至关重要的，因为健康老龄化人口的扩张仍然会表现出认知能力的下降，而认知能力的下降却不足以达到预期的效果。痴呆症但仍会影响功能能力、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与年龄相关的认知变化背后的一种神经化学机制，并提供有关如何发生变化的信息。先前的研究表明，烟碱系统对健康成年人的注意力和记忆力有影响，最近，随着脑功能磁共振成像（fMRI）与精神药理学操作的结合使用的增加，已经出现的数据模式进一步定义了烟碱系统在认知、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表现和大脑激活的年龄差异的原因。通过检查大脑对烟碱阻断和刺激的激活模式，我们发现，与年轻人相比，老年人的内侧额回（MFG）激活增加，我们认为烟碱系统的暂时拮抗作用将模拟这种“老年模式”。我们发现，与年轻人相比，烟碱阻断后，老年人会出现更大的行为障碍和 MFG 激活增加。我们发现，烟碱刺激会提高表现，并且与年轻人相比，老年人的这种改善会更大。我们还将观察到，与年轻人相比，老年人的 MFG 激活会更大。这些数据将进一步了解与正常衰老相关的一种神经化学机制以及大脑激活模式与受体功能的关系。随着对安全有效的认知增强剂的不断探索，了解烟碱系统的作用将变得非常重要。认知老化以及是否烟碱机制有可能有益于健康成年人的认知。