Brain insulin resistance as a mechanistic mediator links peripheral metabolic disorders with declining cognition

Background and aims: Studies continue to investigate the underlying mechanism of the association between the increased risk of different types of cognitive decline and metabolic dysregulation. Brain insulin resistance (BIR) has been suggested to explain this association. The vital role of insulin in the body has been examined intensively and extensively; however, its role in the brain requires further investigation. Herein, we confined our focus to summarize the role of brain insulin signaling and the negative effect of dysmetabolism on insulin functioning in the brain. Methods: Published scientific manuscripts between 1998 and 2020 that discussed the effect of selected metabolic disorder conditions such as obesity, type 2 diabetes mellitus (T2DM), and high-fat diet (HFD) on brain functions were reviewed. The main keywords used were insulin resistance, brain insulin resistance, obesity, T2DM, and cognition. Results: Various metabolic disorders were linked to the increased risk of BIR, and was suggested to increase the probability of cognition impairment occurrence. Several proposed mechanisms explain this association among which insulin resistance and hyperinsulinemia were primary factors attributed to an increased risk of BIR among various metabolic disorders. Conclusions: Understanding the trajectory of the association between metabolic disorders and alternation in cognition status could expand our vision of those overlapping conditions and pave the road to both treatment and preventative strategies for cognitive disorders.(c) 2022 Published by Elsevier Ltd on behalf of Diabetes India.