title: Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose.
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 in AD.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Wash 98108, USA. scraft@u.washington.edu
authors.forename: S
authors.initials: S
authors.lastname: Craft
authors.forename: S
authors.initials: S
authors.lastname: Asthana
authors.forename: J W
authors.initials: JW
authors.lastname: Newcomer
authors.forename: C W
authors.initials: CW
authors.lastname: Wilkinson
authors.forename: I T
authors.initials: IT
authors.lastname: Matos
authors.forename: L D
authors.initials: LD
authors.lastname: Baker
authors.forename: M
authors.initials: M
authors.lastname: Cherrier
authors.forename: C
authors.initials: C
authors.lastname: Lofgreen
authors.forename: S
authors.initials: S
authors.lastname: Latendresse
authors.forename: A
authors.initials: A
authors.lastname: Petrova
authors.forename: S
authors.initials: S
authors.lastname: Plymate
authors.forename: M
authors.initials: M
authors.lastname: Raskind
authors.forename: K
authors.initials: K
authors.lastname: Grimwood
authors.forename: R C
authors.initials: RC
authors.lastname: Veith
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010919:Placebos; D012965:Sodium Chloride; D013004:Somatostatin; D005947:Glucose; D015282:Octreotide