Effects of insulin and octreotide on memory and growth hormone in Alzheimer's disease.
Both insulin alone and the somatostatin analogue octreotide alone facilitate memory in patients with Alzheimer's disease (AD). Since octreotide inhibits endogenous insulin secretion, the cognitive effects of insulin and octreotide may not be independent. This study tested the individual and interactive effects of insulin and octreotide on memory and plasma growth hormone (GH) levels in older adults. Participants were 16 memory-impaired (AD = 7, amnestic mild cognitive impairment = 9; apolipoprotein E [APOE] epsilon4- [no epsilon4 alleles] = 9, epsilon4+ [1-2 epsilon4 alleles] = 7), and 19 cognitively-intact older adults (APOE epsilon4- = 17, epsilon4+ = 1). On separate days, fasting participants received counterbalanced infusions of: 1) insulin (1 mU.kg(-1).min(-1)) and dextrose to maintain euglycemia; 2) octreotide (150 microg/h); 3) insulin, dextrose, and octreotide; or 4) saline. Story recall was the principal endpoint. Insulin alone facilitated delayed recall for epsilon4- patients, relative to epsilon4+ patients (P = 0.0012). Furthermore, epsilon4- patients with higher Mattis Dementia Rating Scale (DRS) scores had greater octreotide-induced memory facilitation (P = 0.0298). For healthy adults, octreotide facilitated memory (P = 0.0122). Unexpectedly, hyperinsulinemia with euglycemia increased GH levels in healthy controls (P = 0.0299). Thus, insulin and octreotide appear to regulate memory in older adults. APOE epsilon4 genotype modulates responses to insulin and octreotide. Finally, insulin may regulate GH levels during euglycemia.
Watson
G Stennis
GS
Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, WA, USA.
Baker
Laura D
LD
Cholerton
Brenna A
BA
Rhoads
Kristoffer W
KW
Merriam
George R
GR
Schellenberg
Gerard D
GD
Asthana
Sanjay
S
Cherrier
Monique
M
Craft
Suzanne
S
D000109:Acetylcholine / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015992:Body Mass Index; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D015282:Octreotide / Q000494:pharmacology*; D013004:Somatostatin / Q000097:blood* / Q000187:drug effects*
D001057:Apolipoproteins E; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D013004:Somatostatin; D000109:Acetylcholine; D015282:Octreotide