Second, alterations in the pattern of regional brain activity due to IR and prolonged hyperglycemia can lead to neuronal damage and a subsequent decline in brain activity (Figure 2) (Heurling et al. 2020; Rebelos et al. 2021); one mechanism is that higher insulin levels can bind to insulin‐degrading enzyme, which also has an active site for Aβ peptides, thereby down‐regulating the breakdown of Aβ plaques by this enzyme (Tian et al. 2023). This evidence concerns the gene INS and Hyperglycemia.