GLUCOSE REGULATION AND MEMORY IN ALZHEIMERS DISEASE

阿尔茨海默病中的葡萄糖调节和记忆

• 批准号: 2052108
• 负责人: SUZANNE CRAFT
• 金额: $ 10.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-10 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2052108
• 关键词: Alzheimer's disease; aging; blood glucose; cognition; cortisol; dietary carbohydrates; gender difference; glucose metabolism; hormone regulation /control mechanism; human old age (65+); human subject; hyperglycemia; hyperinsulinism; injection /infusion; insulin; longitudinal human study; memory disorders; nutrition related tag; oral administration; performance; voltage /patch clamp

Impaired glucose regulation appears to correspond with memory decline in aging, and patients with probable Alzheimer's Disease (AD) show particular abnormalities of glucose utilization and regulation. In particular, patients with probable AD show improved memory accompanied by abnormal increases in insulin during hyperglycemia. Preliminary results also show that memory is enhanced for adults with probable AD when plasma insulin levels are raised while plasma glucose is maintained at baseline. These findings suggest that disruption of baseline. These findings suggest that disruption of basic aspects of glucose regulation and utilization may contribute to memory impairment in probable AD. To further examine this hypothesis, four studies are proposed: Study 1 will determine the combined and unique effects of hyperglycemia and hyperinsulinemia on memory performance and glucoregulatory hormone levels in patients with probable AD by examining memory performance during hyperglycemia with basal insulin, during hyperinsulinemia with basal plasma glucose, and when both insulin and glucose raised to predetermined levels; Study 2 will examine dose response curves for glucose in normal elderly adults and adults with probable AD to explore previous findings that hyperglycemic memory facilitation occurs at different plasma glucose levels for some subjects with mild probable AD than for normal elderly; Study 3 will document whether longitudinal changes in glucose regulation are associated with progressive cognitive decline that characterizes probable AD as has been suggested by previous findings that changes in insulin and cortisol levels are closely associated with the progression of dementia; Study 4 will examine dose response curves for 4 different insulin infusion rates to investigate the effects of different insulin levels on memory performance in patients with probable AD and healthy elderly adults. The results of these studies will provide important information about mechanisms disrupting glucose regulation in probable AD, and about the role these mechanisms play in the cognitive deficits that characterize the disorder.

葡萄糖调节受损似乎与记忆力下降相关 衰老和可能患有阿尔茨海默病 (AD) 的患者表现出特别的 葡萄糖利用和调节异常。 尤其， 可能患有 AD 的患者表现出记忆力改善并伴有异常 高血糖期间胰岛素增加。 初步结果还显示 当血浆胰岛素注射时，可能患有 AD 的成年人的记忆力会增强 水平升高，而血浆葡萄糖维持在基线。 这些 研究结果表明基线被破坏。 这些发现表明 葡萄糖调节和利用的基本方面的破坏可能 导致可能的 AD 的记忆障碍。 为了进一步检验这一点 假设，提出四项研究： 研究 1 将确定综合 高血糖和高胰岛素血症对记忆的独特影响 可能患有糖尿病的患者的表现和葡萄糖调节激素水平 通过使用基础值检查高血糖期间的记忆表现来进行 AD 胰岛素，在高胰岛素血症和基础血浆葡萄糖期间，以及当两者 胰岛素和葡萄糖升高至预定水平；研究 2 将检查 正常老年人和患有糖尿病的成年人的葡萄糖剂量反应曲线 可能的 AD 探索以前的发现，即高血糖记忆 对于某些受试者，在不同的血浆葡萄糖水平下会发生促进作用 与正常老年人相比，AD 的可能性较轻；研究 3 将记录 葡萄糖调节的纵向变化是否与 进行性认知能力下降，可能是 AD 的特征 先前的研究结果表明胰岛素和皮质醇水平的变化 与痴呆症的进展密切相关；研究 4 将 检查 4 种不同胰岛素输注速率的剂量反应曲线 研究不同胰岛素水平对记忆表现的影响 可能患有 AD 的患者和健康老年人。 结果 这些研究将提供有关机制的重要信息 破坏可能的 AD 中的葡萄糖调节，以及这些作用的作用 机制在表征该疾病的认知缺陷中发挥作用。