The Nicotinic Cholinergic System and Cognitive Aging

胆碱能系统已被证明是主要的神经递质系统负责 痴呆症的认知症状虽然痴呆症的治疗益处是明确的，但仍然不确定的是， 一般胆碱能系统和烟碱系统在健康人认知中的作用 非痴呆的老年人（在本申请中称为认知老化）。这一点至关重要，因为 尽管如此，健康老龄化人口的扩张仍将显示认知能力的下降， 痴呆症，但仍然影响功能能力，独立性和财务决策。了解 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 潜在的年龄相关的认知变化，并将提供有关尼古丁功能障碍如何影响 健康老年人的认知能力。先前的研究表明，尼古丁系统在注意力和 健康成年人的记忆力最近，随着脑功能磁共振的使用增加， 功能磁共振成像（fMRI）与精神药理学操作相结合，数据模式已经出现， 进一步定义烟碱系统在认知、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 激活模式响应烟碱阻断和刺激。额内侧回（MFG）增加 与年轻的成年人相比，老年人的激活已经被证明。我们建议暂时的对抗 烟碱系统的功能将模拟这种“旧模式”的受损性能和增加的MFG激活。 我们假设老年人将有更大的性能障碍和增加MFG激活 与尼古丁阻断后的年轻人相比。我们还提出，烟碱刺激将导致 更好的性能和减少MFG激活的“年轻模式”。我们假设尼古丁 刺激将改善性能，与老年人相比，老年人的这种改善更大。 年轻的成年人。我们还将观察到MFG激活的减少，与老年人相比，老年人的MFG激活更大。 to young年轻adults成人.这些数据将进一步了解一种神经化学机制， 以及大脑激活模式与受体功能的关系。随着搜寻工作的继续， 和有效的认知增强剂，重要的是要了解尼古丁系统在认知中的作用， 衰老以及烟碱机制是否有可能有益于健康成年人的认知。

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.