Improving effect of intranasal administration of insulin on memory in man

Insulin has been shown to cross the blood/brain barrier via an active, receptor mediated transport. Its receptors are widely distributed in the brain. Previous studies in different species including man have shown that insulin improves simple memory abilities like the recall of words. The relevance of insulin in memory functions is accented in Alzheimer’s disease, the severity of which correlates inversely to insulin concentrations in the cerebrospinal fluid. However, the therapeutic use of the beneficial effects of insulin on cognitive functions has been hampered by the fact that simultaneous infusion of insulin and glucose is not practicable for a longer time. Recently, we have demonstrated that insulin without absorption enhancers directly enters the cerebrospinal fluid compartment after intranasal administration without measurable changes in blood glucose and plasma insulin levels.

Here we investigated the effect of intranasal administration of insulin (human regular insulin 4×40 IU/d for 8 weeks) or placebo on declarative memory (recall of word lists containing 10 neutral, 10 emotional and 10 food-related words) in 38 healthy subjects (24 males) in a double blind, between subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and the insulin condition. Baseline adjusted recall of words significantly improved after 8 weeks of intranasal insulin administration compared to intranasal placebo treatment (words recalled, placebo 2,92±1.00, insulin 6,20±1,03, p ≤0.038). Moreover, subjects reported a significant increase in the feelings of self-confidence (p ≤0.029) and extroversion (p ≤0.009) and a decrease in the feelings of anger (p ≤0.008) and depression (p ≤0.02) compared to placebo administration. These results indicate that intranasal administration of insulin without absorption into the blood stream improves memory capabilities in healthy subjects. This could be of clinical relevance for the treatment of patients with memory disorders like Alzheimer’s disease.