TNF and obesity due to melanocortin 4 receptor deficiency: High total cholesterol levels in midlife increase the risk of AD nearly threefold: the odds ratio (OR) is 2.8 (95% confidence interval, CI: 1.2–6.7).216 Midlife obesity is also a risk factor for AD,217 and midlife adiposity may predict an earlier onset of dementia and Aβ accumulation.218 Adipose tissue secretes some inflammation factors, such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and interleukin-6, in obesity,219 and these factors may induce insulin resistance, produce Aβ deposits, and stimulate excessive tau phosphorylation.220