APOE and obesity due to melanocortin 4 receptor deficiency: In contrast, carrying the APOE4 allele may be associated with a decreased risk for type 2 diabetes and obesity.7,8 Potentially modifiable metabolic risk factors measured in midlife such as hypertension,9 hypercholesterolemia,10 obesity,11 type 2 diabetes,12,13 and insulin resistance14 increase the risk for late-life dementia.3 However, the interplay between these risk factors, APOE genotype and cerebral changes related to AD is still unclear.