The role of ROS and obesity contributing to the cognitive decline was studied by Toyama et al., 2015, showing that ASK1 is involved in cognitive decline due to long-term high-fat diets through hypoperfusion caused by hypoxia-induced injury and tumor necrosis factor alpha (TNF-α) induction [114]. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.