Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose.
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 in AD.
Craft
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S
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Wash 98108, USA. scraft@u.washington.edu
Asthana
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Newcomer
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Wilkinson
C W
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Matos
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Baker
L D
LD
Cherrier
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M
Lofgreen
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C
Latendresse
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Petrova
A
A
Plymate
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Raskind
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Grimwood
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Veith
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D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000523:psychology*; D001288:Attention / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D006946:Hyperinsulinism / Q000139:chemically induced; D007328:Insulin / Q000097:blood* / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D015282:Octreotide / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D010919:Placebos; D012965:Sodium Chloride / Q000008:administration & dosage / Q000097:blood; D013004:Somatostatin / Q000097:blood* / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D010919:Placebos; D012965:Sodium Chloride; D013004:Somatostatin; D005947:Glucose; D015282:Octreotide