Intranasal Insulin for Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Systematic Review and Meta-analysis

ABSTRACT

OBJECTIVE: There is recent evidence that insulin resistance is responsible for increasing the risk of developing cognitive dysfunction. To systematically review the influence of intranasal insulin treatment on the cognitive function in Alzheimer's disease patients. METHODS: Randomized controlled trials comparing the cognitive effects of intranasal insulin therapy in Alzheimer's disease patients with controlled interventions were retrieved from Pubmed, Medline, Embase and Cochrane library. Meta-analysis was conducted on the cognitive measurements with a subgroup analysis by dose, gender and apolipoprotein E allele 4 (ApoE ε4) status. RESULTS: Seven randomized controlled trials were eligible for inclusion. Intranasal insulin had a positive influence on the cognitive function as compared to placebo without a statistical significance (standardized mean difference; SMD = 0.109; 95% confidence interval; CI −0.04 to 0.26; P=0.14). In subgroup analysis, a 20 IU dose of intranasal insulin induced a significant improvement in cognitive function (SMD = 0.14; 95% CI 0.05 to 0.24; P=0.004), but 40 IU did not show this effect (SMD = −0.01; 95% CI −0.11 to 0.09; P=0.82). ApoE ε4 positive patients showed a significant decline in cognitive function as compared to ApoE ε4 positive patients in the control group (SMD = −0.213; 95% CI −0.38 to −0.04; P=0.015). Such an effect was not apparent in ApoE ε4 negative patients. Gender had no influence on the cognitive outcomes. CONCLUSION: The results indicate that intranasal insulin may have beneficial effect in improving the cognitive function in Alzheimer's disease patients.