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Effects of insulin and octreotide on memory and growth hormone in Alzheimer’s disease

Authors

Watson, G. Stennis, Baker, Laura D., Cholerton, Brenna A., Rhoads, Kristoffer W., Merriam, George R., Schellenberg, Gerard D., Asthana, Sanjay, Cherrier, Monique, Craft, Suzanne

Journal

Journal Of Alzheimer's Disease: JAD, Volume: 18, No.: 3, Pages.: 595-602

Year of Publication

2009

Abstract

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.;

Keywords

acetylcholine, aged, alzheimer disease, apolipoproteins e, blood, body mass index, cognition disorders, diagnosis, drug effects, female, gastrointestinal agents, genetics, humans, hypoglycemic agents, insulin, male, memory, metabolism, neuropsychological tests, octreotide, pharmacology, somatostatin

Countries of Study

USA

Types of Dementia

Alzheimer’s Disease, Mild Cognitive Impairment (MCI)

Types of Study

Before and After Study

Type of Outcomes

Cognition

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Other