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: 3921865
• 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/3921865
• 关键词: Alzheimer's disease; MAO inhibitors; aging; anticholinergic agent; anxiety; arecoline; behavior test; cholinergic agents; clinical depression; depression; dosage; drug adverse effect; human old age (65+); human subject; human therapy evaluation; human tissue; longitudinal human study; memory disorders; naloxone; neuropharmacology; neuropsychological tests; nicotine; opiate alkaloid; psychobiology; psychopharmacology; scopolamine

The pharmacologic challenge model continues to be the major research strategy of the Unit on Geriatric Psychopharmacology. By using drugs to investigate underlying biologic function, we are testing potential diagnostic methods, while simultaneously attempting to develop new drug treatments. This past year, we concluded major studies on Alzheimer's disease, a condition with known cholinergic neuropathology, with two cholinergic agents, arecoline and nicotine. These studies follow our earlier findings of higher functional sensitivity of Alzheimer patients than normal controls or elderly depressives to the anticholinergic agent, scopolamine, which suggest that the cholinergic system in Alzheimer's disease still responds to exogenous drug manipulations. These findings have also led to the development of our latest pilot studies with non-cholinergic medications such as the serotonin agonist, m-chlorophenylpiperazine (m-CPP), and the neuropeptide, thyrotropin-releasing hormone (TRH). With the high degree of overlapping symptoms between geriatric depression and dementia, it is essential to evaluate patients carefully. Consequently, we have systematically compared and contrasted these two major geriatric disorders to ensure diagnostic accuracy and to understand better the common pathologic mechanisms. Given the lack of definitive diagnostic markers, we developed special rating scales to measure depression and daily functioning in dementia subjects. Biological specimens such as cerebrospinal fluid have also been tested to help differentiate depressed and demented patients from age-matched controls. In addition, extensive cognitive testing provides us with an important profiling tool. Together, these instruments allow us to assess the effectiveness of our ongoing medication studies and will enable us to continue our correlative and longitudinal studies in the future.

药理学挑战模型继续是主要的 老年心理药理学单位的研究策略。 经过 使用药物研究潜在的生物学功能，我们是 测试潜在的诊断方法，同时 试图开发新药物治疗。 过去一年，我们 总结了关于阿尔茨海默氏病的主要研究，这种状况 已知的胆碱能神经病理学，有两种胆碱能剂， 槟榔和尼古丁。 这些研究遵循我们的早期发现 阿尔茨海默氏症患者的功能敏感性高于正常患者 对抗胆碱能剂的控制或老年人抑制剂， scopolamine，这表明胆碱能系统 阿尔茨海默氏病仍然对外源性药物操纵反应。 这些发现也导致了我们最新的飞行员的发展 非胆碱能药物（例如5-羟色胺）的研究 激动剂，M-氯苯基哌嗪（M-CPP）和神经肽， 甲状腺蛋白释放激素（TRH）。 老年医学之间的高度重叠症状 抑郁和痴呆，评估患者至关重要 小心。 因此，我们已系统地比较 对比了这两种主要的老年疾病，以确保诊断 准确性并更好地理解常见的病理机制。 鉴于缺乏明确的诊断标记，我们开发了 特殊评分量表以衡量抑郁和日常功能 在痴呆症受试者中。 生物标本，例如脑脊 还已经对液体进行了测试，以帮助区分抑郁症和 来自年龄匹配的对照组的痴呆患者。 此外， 广泛的认知测试为我们提供了重要的分析 工具。 这些工具一起使我们能够评估 我们正在进行的药物研究的有效性，将使我们能够 将来继续我们的相关和纵向研究。