Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects

胍法辛治疗老年受试者前额认知功能障碍

• 批准号: 7527753
• 负责人: CHRISTOPHER H VAN DYCK
• 金额: $ 38.8万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527753
• 关键词: Adrenergic Receptor; Adult; Adverse event; Affect; Age; Aging; Agonist; Animal Experimentation; Animals; Attention; Attention deficit hyperactivity disorder; Automobile Driving; Behavior; Characteristics; Clinical; Clinical Trials; Cognitive aging; Complex; Computers; Daily; Data; Disease; Disruption; Dose; Double-Blind Method; Elderly; End Point; Event; Floods; Frequencies; Functional disorder; Guanfacine; Hyperactive behavior; Impaired cognition; Internet; Knowledge; Measures; Mediating; Memory; Mind; Patients; Performance; Personal Satisfaction; Placebos; Prefrontal Cortex; Process; Quality of life; Randomized; Relative (related person); Research; Safety; Short-Term Memory; Symptoms; Telephone; Testing; Thinking; Trees; Week; cognitive function; design; distraction; executive function; experience; healthy aging; impression; improved; memory recall; memory recognition; nonhuman primate; pre-clinical research; response; tv watching; Adrenergic Receptor; Adult; Adverse event; Affect; Age; Aging; Agonist; Animal Experimentation; Animals; Attention; Attention deficit hyperactivity disorder; Automobile Driving; Behavior; Characteristics; Clinical; Clinical Trials; Cognitive aging; Complex; Computers; Daily; Data; Disease; Disruption; Dose; Double-Blind Method; Elderly; End Point; Event; Floods; Frequencies; Functional disorder; Guanfacine; Hyperactive behavior; Impaired cognition; Internet; Knowledge; Measures; Mediating; Memory; Mind; Patients; Performance; Personal Satisfaction; Placebos; Prefrontal Cortex; Process; Quality of life; Randomized; Relative (related person); Research; Safety; Short-Term Memory; Symptoms; Telephone; Testing; Thinking; Trees; Week; cognitive function; design; distraction; executive function; experience; healthy aging; impression; improved; memory recall; memory recognition; nonhuman primate; pre-clinical research; response; tv watching

DESCRIPTION (provided by applicant): In an "Information Age" when we are continually flooded with multiple simultaneous inputs, many elderly people struggle with seemingly simple tasks, such as navigating their bank's phone tree, using the remote to watch TV or DVDs, using the increasingly essential computer and internet, or driving the car on ever more complex roadways. We all need our "executive abilities" far more than we did even 20 years ago, and this is a particular challenge for the elderly. A core feature of cognitive aging is the decline in executive functions mediated by the prefrontal cortex. These functions include the ability to keep in mind what has just occurred, or bring to mind knowledge from the past, and use this temporary information to guide behavior. This represented information is critical for inhibiting inappropriate responses and overcoming distraction and interference from previous, now irrelevant memories. Prefrontal executive functions are key for planning, maintaining attention, and storing and recalling memories, especially when it is an effortful process. Although prefrontal executive dysfunction is a characteristic and disabling feature of aging, no treatment has been developed to date-or even tested, to our knowledge-for the amelioration of these symptoms. Yet, two decades of research in animals has demonstrated that the executive functions of the prefrontal cortex can be improved by alpha-2 adrenoreceptor agonists. The alpha-2A-agonist, guanfacine, is well-tolerated and has already demonstrated benefit in patients with attention deficit hyperactivity disorder. However, guanfacine has thus far not been tested for its ability to restore executive function in elderly adults, despite the evidence from preclinical research that the elderly are the most likely to experience its benefit. This proposal aims to determine whether low doses of the alpha-2A-agonist guanfacine can improve deficits in prefrontally-mediated executive functions in healthy elderly (=75 years) subjects. Subjects (N=90) will be randomly assigned to receive placebo or guanfacine at one of two dose levels: 0.1 mg daily, or 0.5 mg daily in double-blind fashion for 12 weeks. Subjects will be assessed using composite measures of prefrontal executive function and recognition memory function, a clinical global impression of change, and a quality of life measure. This Pilot Clinical Trial will provide essential preliminary data for a subsequent full-scale trial of guanfacine for prefrontally-mediated cognitive dysfunction in elderly subjects.

描述（由申请人提供）：在“信息时代”中，当我们不断地淹没多个同时输入时，许多老年人都在努力处理看似简单的任务，例如使用越来越多的必不可少的计算机和互联网来浏览其银行的电话树，使用遥控器来观看电视或DVD，或在更复杂的道路上开车。我们所有人都需要我们的“执行能力”远远超过20年前，这对老年人来说是一个特别的挑战。认知衰老的核心特征是前额叶皮层介导的执行功能下降。这些功能包括牢记刚刚发生的事情或从过去的知识中牢记的能力，并使用这些临时信息来指导行为。这代表信息对于抑制不适当的反应并克服了以前（现在无关紧要的记忆）的干扰和干扰至关重要。前额叶执行功能是计划，保持关注以及存储和回忆记忆的关键，尤其是在这是一个艰苦的过程时。尽管前额叶的执行功能障碍是衰老的特征和残疾人，但未开发治疗日期至测试，甚至对我们的知识改善这些症状。然而，在动物中进行了二十年的研究表明，α-2肾上腺受体激动剂可以改善前额叶皮层的执行功能。 α-2A激动剂鸟汀（Guanfacine）具有良好的耐受性，并且已经证明了注意力缺陷多动障碍的患者有益。然而，迄今为止，鸟法氨酸尚未获得恢复老年人执行职能的能力，尽管临床前研究的证据表明，老年人最有可能经历其受益。该提案旨在确定低剂量的α-2a激动剂鸟丝是否可以改善健康老年人（= 75年）受试者的前额叶介导的执行功能的缺陷。受试者（n = 90）将随机分配以两种剂量水平之一：每天0.1 mg或每天0.5 mg以双盲方式接收安慰剂或鸟汀。将使用前额叶执行功能和识别记忆功能，临床全球变化印象以及生活质量度量的综合度量来评估受试者。这项试验临床试验将为随后对鸟明的全尺度试验提供基本的初步数据，用于老年受试者的前额叶介导的认知功能障碍。