Results:
Eight studies (328 participants) were analyzed. No significant side effects of intranasal insulin administration were reported. Seven studies included healthy subjects' response to intranasal insulin, and three evaluated the cognitive effect among patients with minimal cognitive impairment or overt Alzheimer's disease. In healthy people, Cohen's effect size calculations suggest that only 160 IU/d intranasal insulin induced potential beneficial effects. Although females, when compared head-to-head, exhibited greater improvements in cognitive tests than men, the composite analysis of all included studies did not support this trend. Among cognitively impaired patients, only lower doses of insulin were assessed, and 20 IU revealed potential beneficial effects on cognitive functions. This was significant in a single study assessing long-term intranasal insulin administration, whereas acute administration of 20 IU intranasal insulin tended to show a beneficial effect on immediate recall in Apo ε4(−), but not Apo ε4(+), patients.