Effects of Insulin and Octreotide on Memory and Growth Hormone in Alzheimer's Disease

Article type: Research Article

Authors: Watson, G. Stennis^{a; b} | Baker, Laura D.^{a; b} | Cholerton, Brenna A.^{a; b} | Rhoads, Kristoffer W.^{a; b; c} | Merriam, George R.^{d; e} | Schellenberg, Gerard D.^{a; e; f; g; h} | Asthana, Sanjayⁱ | Cherrier, Monique^{b; j} | Craft, Suzanne^{a; b; *}

Affiliations: [a] Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, WA, USA | [b] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA | [c] Physical Medicine and Rehabilitation (G2-PMR), Virginia Mason Medical Center, Seattle, WA, USA | [d] Medicine Service, VA Puget Sound Healthcare System, Seattle, WA, USA | [e] Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA | [f] Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA | [g] Department of Pharmacology, University of Washington School of Medicine, Seattle, WA, USA | [h] Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA | [i] GRECC, William S. Middleton Memorial Veterans Hospital and Department of Medicine, University of Wisconsin Medical School, Madison, WI, USA | [j] Mental Illness Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, WA, USA

Correspondence: [*] Corresponding author: Dr. Suzanne Craft, VAPSHCS, S-182-GRECC, 1660 South Columbian Way, Seattle, WA 98108, USA. Tel.: +1 206 277 1156; Fax: +1 206 764 2569; E-mail: [email protected].

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] ε4- [no ε4 alleles] = 9, ε4+ [1–2 ε4 alleles] = 7), and 19 cognitively-intact older adults (APOE ε4- = 17, ε4+ = 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 μg/h); 3) insulin, dextrose, and octreotide; or 4) saline. Story recall was the principal endpoint. Insulin alone facilitated delayed recall for ε4- patients, relative to ε4+ patients (P = 0.0012). Furthermore, ε4- 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 ε4 genotype modulates responses to insulin and octreotide. Finally, insulin may regulate GH levels during euglycemia.

Keywords: Acetylcholine, Alzheimer's disease (AD), apolipoprotein E (APOE), growth hormone (GH), insulin, memory, mild cognitive impairment (MCI), octreotide, somatostatin

DOI: 10.3233/JAD-2009-1165

Journal: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 595-602, 2009