Intranasal Insulin Boosts Cognitive Function

Dr. Assaf Rudich of Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues note that accumulating mechanistic evidence suggests that the brain is a previously unrecognized target of insulin and that the effects "may range widely, from regulation of eating and appetite to affecting cognitive functions."

Dr. Rudich added that, "Although the current clinical evidence is limited, there are initial indications that high doses administered to healthy persons can result in mild improvements in scores of various tests assessing cognitive function." Lower doses may be effective in the cognitively impaired.

In a systematic review the researchers examined data from eight trials of intranasal insulin involving 328 subjects. The intranasal route, they note, "can assist in minimizing the systemic effects of the drug, which in the case of insulin are obviously very significant."

Six of the trials enrolled only people with normal cognition, one trial enrolled normal subjects and people with mild cognitive impairment (MCI) or Alzheimer's disease (AD), and one enrolled only patients with MCI or AD. Insulin doses ranged from 20 to 160 IU per day.

One study compared men to women head-to-head and suggested that women gained more benefit. The other studies did not support this trend.

Four of the seven studies with cognitively normal subjects showed a benefit for 160 IU but not with doses of 60 IU or less. In the cognitively impaired, one study showed a benefit with 20 IU, another showed a trend, and the third study showed no benefit.

There seemed to be a benefit in patients who were Apo e4 negative, but not in those who were Apo e4 positive.

The investigators also saw data to suggest that intranasal insulin improves verbal working memory in humans. In rodents, they note, the frontal cortex is characterized by a relative high density of insulin receptors.

The authors say their findings indicate directions for further research. For instance, "the insulin concentrations achieved by intranasal administration and insulin's dispersion in the various brain regions involved in memory functions are unclear."

"Dementia is a growing problem with the aging population," added Dr. Rudich, "and we hope our summary will inspire further advancements in this important area."

J Clin Endocrinol Metab Dec. 2011.