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下降相对应 衰老，患有阿尔茨海默氏病（AD）的患者特殊 葡萄糖利用和调节的异常。 尤其， 可能的AD患者显示出改善的记忆力，伴有异常 高血糖期间胰岛素的增加。 初步结果也显示 血浆胰岛素时可能会增加可能AD的成年人的记忆力 在基线时保持等离子体葡萄糖时，水平升高。 这些 调查结果表明基线的破坏。 这些发现表明 葡萄糖调节和利用的基本方面的破坏可能 在可能的AD中有助于记忆障碍。 进一步研究 假设提出了四项研究：研究1将确定合并的合并 高血糖和高胰岛素血症对记忆的独特影响 可能患者的性能和糖调节激素水平 通过检查高血糖期间的记忆表现，以基础检查 胰岛素，在高胰岛素血症的基础血浆葡萄糖期间，当 胰岛素和葡萄糖升高到预定水平；研究2将检查 正常成年人和成年人的葡萄糖的剂量反应曲线 可能探索高血糖记忆的先前发现的广告 某些受试者的促进性发生在不同的血浆葡萄糖水平 与正常老年人相比，有可能的AD轻度广告；研究3将记录 葡萄糖调节的纵向变化是否与 逐渐认知的逐渐下降，表征了可能的广告 先前的发现提出，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 检查剂量反应曲线的4种不同的胰岛素输注率 研究不同胰岛素水平对记忆性能的影响 在可能的AD和健康的老年人的患者中。 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 机制在特征该疾病的认知缺陷中发挥作用。