Produced in the pancreatic β cells, insulin enters the brain by a receptor-mediated, saturable transport mechanism, and brain insulin levels are proportional to peripheral levels under physiologic conditions.6, –, 9 A U-shaped association between serum insulin and dementia is therefore plausible on the basis of clinical evidence regarding hyperinsulinemia10 and insulin deficiency in the brain.7,11,12 It has been pointed out that the latter could also be a consequence of previous peripheral hyperinsulinemia and T2DM.7,8,13. This evidence concerns the gene INS and Hyperinsulinemia.