Lowering risk of Alzheimer’s disease
Medical, dietary, and lifestyle choices may promote healthy brain aging
The apolipoprotein E epsilon 4 (APOE e4) gene may explain, at least in part, the conflicting results of these studies. In 2 population-based cohorts,12,13 smoking was associated with memory decline in patients without, but not with, the APOE e4 genotype.
Dietary factors
Antioxidants. The brains of patients with AD contain elevated levels of endogenous antioxidants. In vitro studies show exogenous antioxidants can reduce the toxicity of beta-amyloid in brain tissue of persons with AD. These findings have led to interest in assessing the role of dietary antioxidants such as vitamins E and C for AD prevention.
High-dose alpha-tocopherol (vitamin E, 2,000 IU/d) may slow disease progression in patients with AD, but this association is not consistently found. Furthermore, a meta-analysis of 19 randomized controlled trials (RCTs) totaling >135,000 patients found an association between vitamin E doses >400 IU/d and increased all-cause mortality.14 High-dose vitamin E supplementation for primary or secondary prevention of AD may be dangerous and is not recommended.
The lack of consistent efficacy data for vitamin C in preventing or treating AD may discourage its routine use for this purpose.15
Homocysteine is a risk factor for stroke and heart disease. It also could play a role in vascular dementia through its association with large- and small-vessel disease.
Low folate and hyperhomocysteinemia have been associated with dementia or cognitive impairment, although a cause-effect relationship is not clear. In non-demented elderly populations, plasma homocysteine is inversely associated with poor performance in tests of global cognitive function, particularly in measures of psychomotor speed.
In a recent double-blind RCT, folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age, especially information processing and sensorimotor speed.16 No other good evidence, however, has shown that homocysteine-lowering therapy using folic acid or other vitamin B supplements improves cognitive function or prevents cognitive decline.
Fish and omega-3 fatty acids. High total fat, saturated fat, and total cholesterol intake increases the risk for incident dementia. In epidemiologic studies, low omega-3 fatty acid serum levels have been linked to increased dementia risk.
Fish consumption may be beneficial in reducing the risk of dementia or cognitive decline. A prospective study of 815 elderly persons found 60% less risk of developing AD in those who ate ≥1 fish meal per week, compared with those who rarely or never ate fish.17 In the Framingham study, individuals who at baseline were in the top quartile of docosahexaenoic acid consumption had lower dementia rates over 9 years of follow-up.18 Results from cross-sectional and longitudinal studies have been inconsistent; some have shown that high intake of n-3 polyunsaturated fatty acids is associated with less cognitive decline,19 whereas others have not.20
Although we cannot offer unequivocal advice regarding seafood or omega-3 fatty acid intake for primary prevention of dementia without evidence from RCTs, these uncontrolled studies show promise.
Mediterranean diet (MeDi) components include abundant fruits and vegetables, fish or shellfish at least twice weekly, very limited red meat, olive oil or canola oil instead of butter or margarine, tree nuts such as walnuts or pecans, red wine in moderation, and using herbs and spices instead of salt to season food. High adherence to the MeDi has been associated with a significantly lower risk for incident AD. The MeDi may affect the risk of developing AD21 as well as subsequent disease course, with a possible dose-response relationship in lower mortality.22
Eating fruits and vegetables has been associated with improved cognitive performance22 and decreased incident dementia in elderly subjects.18
Alcohol. A U-shaped relationship exists between alcohol consumption and dementia risk. High alcohol intake is associated with clinical problem drinking and alcoholism and can lead to cognitive decline. Conversely, moderate wine consumption (250 to 500 mL/d) may be protective—compared with more or less than this amount—and is associated with approximately 50% less risk of dementia.
Alcohol use may increase the risk of dementia in persons carrying the APOE e4 allele, according to the population-based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study from Sweden.23 After an average 21 years of follow-up of 1,449 individuals, researchers found that environmental factors—such as physical inactivity, dietary fat intake, alcohol consumption, and smoking at midlife—were associated with an increased risk of dementia at age 65 to 79 in APOE e4 carriers compared with noncarriers. The study also found that physical inactivity, dietary fat intake, and smoking at midlife increase AD risk, especially among APOE e4 carriers.
