NEUROPHARMACOLOGY OF COGNITION AND MOOD IN GERIATRIC NEUROPSYCHIATRY

老年神经精神病学中认知和情绪的神经药理学

• 批准号: 6162823
• 负责人: T SUNDERLAND
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162823
• 关键词: Alzheimer's disease; acetylcholine; aging; biomarker; brain disorder chemotherapy; cholinesterase inhibitors; clinical research; clinical trials; cognition; disease /disorder proneness /risk; family genetics; human old age (65+); human subject; human therapy evaluation; mecamylamine; memory disorders; neural degeneration; neuropharmacology; psychopharmacology; scopolamine

To better understand the pharmacologic underpinnings of human memory, we have pursued a "pharmacologic challenge" strategy which involves attempts to model the memory of Alzheimer's disease (AD) in older volunteers (protocol 83-M-0123). After testing numerous medications, we have discovered that a combination of the nicotinic antagonist, mecamylamine, with the central muscarinic antagonist, scopolamine, has proved most effective in briefly modeling the memory impairment of AD. This data is consistent with previously published brain imaging literature, and once more emphasizes the central importance of the cholinergic system in human memory. We are also focusing on the testing of subjects "at risk" for developing AD on the basis of family history and age (protocol 95-M-0096). As part of this study, we are looking for evidence of increased sensitivity to cholinergic blockade in these subjects, even before they manifest signs of cognitive decline. It is our hypothesis that this test might serve as a early diagnostic marker for the disease process. In addition, we are treating AD patients chronically with the anticholinergic scopolamine to determine if they are capable of cholinergic upregulation and increased response to cholinesterase inhibitors (protocol 95-M-0096). This study could have an immediate impact on treatment strategies with AD.

为了更好地了解人类记忆的药理基础，我们 采取了“药理挑战”策略，涉及尝试 模拟老年志愿者中阿尔茨海默氏病（AD）的记忆 （协议83-m-0123）。 测试了许多药物后，我们有 发现烟碱拮抗剂Mecamylamine的结合， 与中央毒蕈碱拮抗剂Scopolamine一起证明了最多 有效地简要建模AD的内存障碍。 这个数据是 与先前发表的脑成像文献一致，一次 更强调胆碱能体系在人类中的核心重要性 记忆。 我们还专注于开发“处于风险”的主题的测试 基于家族史和年龄的广告（协议95-m-0096）。 作为一部分 在这项研究中，我们正在寻找对提高敏感性的证据 胆碱能在这些主题中，甚至在表现出迹象之前 认知能力下降。 我们的假设是该测试可能是 疾病过程的早期诊断标记。 此外，我们是 用抗胆碱能骨pol碱长期治疗AD患者 确定它们是否能够上调并增加 对胆碱酯酶抑制剂的反应（方案95-m-0096）。 这项研究 可能会对AD的治疗策略产生直接影响。