Although aging is clearly the dominant risk factor for AD, growing evidence suggests that peripheral insulin resistance with obesity, T2DM, metabolic syndrome (dyslipidemic states), and non-alcoholic steatohepatitis (NASH) mediate brain insulin/IGF resistance, and thereby contribute to the pathogenesis of mild cognitive impairment (MCI), dementia, and AD [5, 6, 25, 26, 50, 51, 84-87]. This evidence concerns the gene INS and Alzheimer disease.