Impaired glucose regulation appears to correspond with memory decline in aging, and patients with probable Alzheimer's Disease (SDAT/DAT) show particular abnormalities of glucose utilization and regulation. Further, normal elderly and SDAT/DAT subjects show improved memory when plasma glucose is elevated to optimal levels. In a previous study, this improvement was accompanied by increased plasma insulin for very mild SDAT/DAT subjects. Based on these findings, the proposed study, examines the effects of hyperglycemia on memory performance and gluco-regulatory hormone levels in patients with mild SDAT/DAT and normal elderly subjects. The study will also examine the specific effects of increased insulin levels on memory performance. Subjects will participate in five conditions: 1. hyperglycemia with plasma insulin kept at baseline with an islet clamp technique; 2. hyperinsulinemia with plasma glucose kept at baseline with glucose infusion; 3. hyperglycemia with plasma insulin allowed to increase naturally; 4. baseline plasma glucose and insulin accompanied by an islet clamp; and 5. baseline plasma glucose and insulin with saline infusion. Glucoregulatory hormones and metabolites will be measured in each condition, as will performance on both memory and non- memory measures. Hormone/metabolite levels and cognitive performance will be compared across conditions to determine if cognitive performance improves in experimental relative to baseline conditions, and if improvement is accompanied by hormonal changes. Finally, subjects will be followed longitudinally to determine if changes in glucose regulation are associated with cognitive changes. The results of the study will provide important information about mechanisms disrupting glucose regulation in SDAT/DAT, and about the role these mechanisms play in the cognitive deficits that characterize the disorder.
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