Impaired glucose regulation appears to correspond with memory decline in aging, and patients with Senile Dementia of the Alzheimer Type (SDAT) show particular abnormalities of glucose regulation as measured by neuropathological and metabolic methods. Further, several investigators have documented that normal elderly and SDAT subjects show improvement in memory function when plasma glucose is elevated to optimal levels. In a preliminary study, this improvement was accompanied by increased plasma insulin for very mild SDAT subjects. Based on these findings, the proposed study examines the effects of hyperglycemia on memory performance and glucoregulatory hormone levels in subjects with mild SDAT compared with normal elderly subjects. The study will also examine the specific effects of increased insulin levels on memory performance. Subjects will participate in three experimental and two baseline conditions: 1. hyperglycemia with plasma insulin maintained at baseline level using an islet clamp technique; 2. hyperinsulinemia with plasma glucose maintained at baseline using glucose infusion; 3. hyperglycemia with plasma insulin allowed to increase naturally; 4. baseline plasma glucose and insulin with an islet clamp; and 5. baseline plasma glucose and insulin with saline infusion. Glucoregulatory hormones and metabolites will be measured in each condition. In addition, cognitive protocols containing both memory and non-memory measures will be administered in each condition. Hormone and metabolite levels and cognitive performance will be compared across conditions to determine if cognitive facilitation occurs in experimental relative to baseline conditions, and if such facilitation is accompanied by corresponding hormonal changes. The results of the proposed study should provide important information about the specific mechanisms disrupting glucose regulation in SDAT, as well as about the role of these mechanisms in producing the cognitive deficits that characterize the disorder.
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