Obesity and Overweight increase risk of AD in APOE4 carriers BOTH directly and indirectly.

 Obesity and overweight increase risk for diabetes. Overweight increases risk of diabetes 3 fold. Obesity increases risk of diabetes 9 fold in study by Weinstein (Physical inactivity and body mass).(52)

In addition, obesity and overweight directly increase risk, by increase in insulin resistance. Insulin resistance causes increases in insulin levels which cause increase in mTOR.

A study in mice showed obesity increased risk of AD in transgenic APOE4 mice, but not in APOE3 mice.

In study quoted above (Lifestyle) high caloric intake increased incidence of MCI 5 fold in APOE4 carriers; but less than 2 fold in non-E4 carriers.(30)