Intranasal insulin improves memory in humans: Superiority of insulin aspart

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-1) is more rapidly absorbed than RH-1 after subcutaneous administration. Since after intranasal insulin administration, ASP-1 may also be expected to access the brain, we examined whether intranasal ASP-1 has stronger beneficial effects on declarative memory than RH-1 in humans. Acute (401U) and long-term (4 x 401U/day over 8 weeks) effects of intranasally administered ASP-1, RH-1, 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-1 (p < 0.01) and the RH-1 groups (p < 0.05). ASP-1-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-1. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.