Diet and lifestyle are of great importance in prevention of AD in APOE4 carriers. This is in contrast in non-E4 carriers in whom diet and life style appear to have minimal impact.
As shown in study presented in "Lifestyle and Risk", Kivipelto study, (28) which followed person in 50-70 age group for 20 years, risk factors had a composite effect. The result was an 11 fold difference from best quartile to worst quartile. In non-E4 there was no composite effect.
As regards specific diet from best to worst quartile:
Saturated fats: 11.3 fold increase in E4 group. In remarkable contrast, non-E4 group Odds ratio was 1.1, a very minimal effect.
Dietary intake polyunsaturated fatty acids 2 fold increase risk.
PUFA are found in plant-based oils such as safflower, corn, sunflower oils. PUFA include Omega-3 fatty acids; which include fatty fish like salmon, mackerel.
Saturated fats which had largest negative impact include meat, poultry, egg yolks, whole-fat dairy products including butter and cheese, baked goods processed foods, crackers, cakes, pies, candies, snack foods, french fries.
Trans fats, also called hydrogenated vegetable oils are very unhealthy.
TOTAL CALORIC INTAKE: High caloric intake very large risk factor for APOE4 carriers. Review Luchsinger paper above, "Caloric intake and risk AD".( 29)
In APOE4 carriers, those in highest third of caloric intake compared with lowest third had 5.2 fold increase of Amnestic MCI. This was a 3 fold greater increased risk compared with non-E4 who's risk increased only 1.7 fold. (30)
The two studies above (29), (30) refer to risk of high caloric intake in APOE4 carriers for AD and MCI, respectively.
Increased caloric intake also major risk factor for being overweight and obesity which are major risk factors for diabetes.
Alcohol intake: In the Kivipelto study, (28) frequent alcohol intake created increased risk 7 fold. This was also in sharp contrast to non-E4 in whom frequent alcohol intake decreased risk with risk factor 0.6. Many studies have shown that moderate wine intake lowered risk for AD; however this was only shown to be true in non-E4 carriers, when APOE status was determined.
Smoking increased risk 2 fold in Kivipelto study; but surprisingly did not increase risk in non-E4 person.(28)
These lifestyle factors, especially saturated fats, alcohol, smoking, high caloric intake show a very different risk for APOE4 carriers vs non-E4.
Coffee intake: "Caffeine as a protective factor in dementia and Alzheimer's disease", Eskelinen, 2010, (84) stated that their results from CAIDE study showed drinking 3-5 cups coffee per day at mid-life was associated with decreased risk of dementia/AD by about 65% in late-life. They also mention that most studies (3 out of 5) support coffee's favorable effects against cognitive decline, dementia and AD.
In regard to coffee, I found no studies about coffee and APOE status. However, the following study is rather convincing as regards coffee and risk of AD in APOE4 carriers.
"Coffee protects against disruption BBB in animal models of AD and Parkinson's disease, Chen, 2010 (85). In mice models equivalent of 3-5 cups coffee protected against of leakage of BBB.
Since a leaky BBB is the fundamental defect in APOE4 carriers; this study certainly suggests coffee may be protective against AD in APOE4 carriers.
There are very large number of papers about nutrition and risk of AD, unfortunately most do not include information about APOE4 status. Unless study has APOE4 status; it is of limited value to APOE4 carriers. The study may not show major risk factor as in case of saturated fats or show opposite effects as regards studies showing moderate wine intake protects against AD while only true for non-E4 persons and alcohol harmful for APOE4 carriers. Since APOE4 carriers only about 20% of population, the non-E4 effect can obscure the effect in APOE4 carriers.
Traumatic brain injury
Part of Lifestyle is engaging in behavior with high risk of traumatic brain injury. One should consider their APOE status before such behavior.
A meta-analysis of APOE4 and outcome after traumatic brain injury (86) stated, "the APOE4 allele was significantly associated with a poor outcome of TBI at 6 month after injury (RR = 1.36).
Activities such as High School and college football might present an acceptable risk to non-E4 carriers; but an unacceptable high risk in APOE4 carriers.