Alzheimer’s disease as a form of in situ diabetes: A systematic review and meta-analysis of therapeutic approaches using intranasal insulin treatment

Abstract

ABSTRACTIntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by the loss of memory, language, and other cognitive functions. Increasing evidence suggests that AD shares pathophysiological similarities with type 2 diabetes, leading to the concept of AD as “diabetes in situ” within the brain. Intranasal insulin (INI) for AD has emerged as a promising therapeutic approach due to its ability to directly target the brain and modulate insulin signaling pathways.ObjectiveTo evaluate the efficacy and safety of INI therapy for AD through a systematic review and meta-analysis of randomized clinical trials.MethodA comprehensive search across electronic databases, including PubMed, Web of Science, Scopus, and Embase, was conducted to identify relevant studies published up to June 2024. Studies were included if they met the following criteria: original research articles published in peer-reviewed journals; focused on humans; investigated the therapeutic effects of INI administration on cognitive impairment associated with AD or diabetes; reported quantitative data on cognitive outcomes, biomarkers, or pathological markers relevant to AD or diabetes. For studies with available data, a meta-analysis was conducted to quantitatively synthesize the effects of INI on cognitive outcomes. METAANALYSISONLINE (https://metaanalysisonline.com/), an online statistical tool, was employed to conduct the meta-analysis and generate forest plots and funnel plots.ResultsA total of 647 articles were identified through electronic database searches using predefined search terms, and eight studies met the inclusion criteria and were selected for data extraction and analysis. Based on the analysis performed using random effects model with Mantel-Haenszel method to compare the odds ratio, the overall odds ratio was 3.75 with a 95% confidence interval of 1.49 - 9.4. The test for overall effect shows a significance at p<0.05. The The I2value indicates that 85.5% of the variability among studies arises from heterogeneity rather than random chance.ConclusionWhile the data is not yet definitive enough to establish INI as a definitive treatment for AD, the accumulating evidence supporting its safety, efficacy, and reduced systemic side effects strongly suggests that INI is associated with an overall enhancement of global cognition.