|dc.description.abstract||Background: Increasing plasma glucose levels improves
memory in patients with Alzheimer disease (AD).
Increasing plasma glucose levels also increases endogenous
insulin levels, raising the question of whether
memory improvement is due to changes in insulin, independent
of hyperglycemia. We address this question
by examining memory and counterregulatory hormone
response during hyperglycemia when endogenous insulin
was suppressed by concomitant infusion 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) hyperinsulinemia (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 [225 mg/dL]) with fasting
insulin (57 pmol/L), achieved by dextrose and somatostatin
(octreotide) infusion (150 mg/h); (3) placebo with
isotonic sodium chloride solution (saline) infusion (fasting
insulin and glucose); and (4) an active control condition
in which somatostatin alone was infused
(150 mg/h). Declarative memory (story recall) and selective
attention (Stroop interference test) were measured
during steady metabolic states.
Results: Patients with AD showed improved memory
during hyperinsulinemia relative to placebo (P = .05) and
relative to hyperglycemia (P,.005). Memory did not improve
during hyperglycemia when insulin was suppressed.
Somatostatin analogue infusion alone also
improved memory for patients with AD (P,.05). Hyperinsulinemia
increased cortisol levels in subjects with
AD, whereas somatostatin alone lowered cortisol concentrations.
Conclusions: These results confirm that elevated
insulin without hyperglycemia enhances memory in
adults with AD, and indicate that insulin is essential
for hyperglycemic memory facilitation. These results
also suggest a potential therapeutic role for somatostatin