Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose

Background: Increasing plasma glucose levels improves memory in patients wi th Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improveme nt is due to changes in insulin, independent of hyperglycemia. We address t his question by examining memory and counterregulatory hormone response dur ing hyperglycemia when endogenous insulin was suppressed by concomitant inf usion of the somatostatin analogue octreotide (Sandostatin). Methods: Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsuline mia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [22 5 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somato statin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium c hloride solution (saline) infusion (fasting insulin and glucose); and (4) a n active control condition in which somatostatin alone was infused (150 mg/ h). Declarative memory (story recall) and selective attention (Stroop inter ference test) were measured during steady metabolic states. Results: Patients with AD showed improved memory during hyperinsulinemia re lative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatosta tin analogue infusion alone also improved memory for patients with AD (P<.0 5). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. Conclusions: These results confirm that elevated insulin without hyperglyce mia enhances memory in adults with AD, and indicate that insulin is essenti al for hyperglycemic memory facilitation. These results also suggest a pote ntial therapeutic role for somatostatin in AD.