1. ¹Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany
2. ²Obesity Centre, Spitalregion St Gallen-Rorschach, Switzerland
3. ³Novo Nordisk Germany, Mainz, Germany
4. ⁴Department of Internal Medicine 1, University of Lübeck, Lübeck, Germany

Correspondence: Dr C Benedict, Department of Neuroendocrinology, University Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, Haus 23a, Lübeck 23538, Germany. Tel: +49 451 500 4602; Fax: +49 451 500 3640; E-mail: benedict@kfg.uni-luebeck.de

Received 9 February 2006; Revised 13 July 2006; Accepted 17 July 2006; Published online 16 August 2006.

Abstract

There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and long-term (4 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (p<0.01) and the RH-I groups (p<0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (p<0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.