MEMORY IMPROVEMENT FOLLOWING INDUCED HYPERINSULINEMIA IN ALZHEIMERS-DISEASE

Dementia of the Alzheimer type (DAT) is accompanied by disruption in g lucose regulation and utilization that may contribute to its character istic memory impairment. Increasing glucose availability by raising pl asma glucose improves memory in patients with DAT. Such memory improve ment is associated with a secondary elevation in plasma insulin levels , raising the question of whether improvement is due to changes in ins ulin levels, independent of hyperglycemia. Distributions of insulin re ceptors in the hippocampus and insulin-mediated increases in glucose u tilization in entorhinal cortex provide potential mechanisms for such improvement. We show that raising plasma insulin through intravenous i nfusion while keeping plasma glucose at a fasting baseline level produ ces striking memory enhancement for patients with DAT. Previous findin gs of hyperglycemic memory enhancement were also replicated. Patients with DAT also showed abnormal plasma levels of glucoregulatory hormone s and metabolites at baseline and during metabolic manipulations. Our findings suggest that neuroendocrine factors play an important role in the pathophysiology of DAT.