Analysis of Link between Brain Insulin Resistance and Alzheimer's Disease: A Systematic Review

Abstract

Abstract Introduction Insulin resistance (IR) is a condition characterized by the inability of cells to respond to insulin, leading to glucose intolerance and hyperglycemia. This condition has been well-documented in peripheral tissues such as liver, muscle, and adipose tissue. However, recent studies suggest that the IR in the brain, also known as brain IR, may play a role in the development of neurodegenerative diseases such as Alzheimer's disease (AD). Objective In this systematic review, we aim to summarize the current knowledge about brain insulin resistance (BIR) and its potential implications in neurodegenerative diseases. Methods A systematic search of PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted using the keywords "insulin resistance", “brain insulin resistance”, "Alzheimer's disease", "neurodegeneration", and "cognition". The search was limited to articles published in English from 2000 to 2023. Studies were included if they investigated the role of BIR in neurodegenerative diseases or if they provided insights into the mechanisms involved in BIR. A total of 17 articles were included in this review. Results BIR has been observed in various neurodegenerative diseases such as AD. Studies suggest that BIR may contribute to the cognitive impairment seen in these diseases. Insulin plays an important role in regulating glucose metabolism, neuronal energy production, and synaptic plasticity in the brain. BIR leads to impaired glucose uptake and utilization, decreased ATP production, and alterations in synaptic plasticity, which ultimately affect cognitive function. Conclusion BIR is emerging as an important factor in the pathogenesis of neurodegenerative diseases, particularly AD. By targeting BIR, novel therapeutic strategies may be developed for the treatment and prevention of these devastating diseases.