We did MEDLINE searches with the terms: “diet”, “antioxidants”, “vitamin E (tocopherol)”, “vitamin C (ascorbic acid)”, “carotenes”, “fats”, “fish”, “fatty acids”, “alcohol”, “homocysteine”, “vitamin B6”, “vitamin B12”, “folate and folic acid”, “cognitive function”, “dementia”, and “Alzheimer's disease” from 1990 to June 2004. We also included data from our own publications. We favoured results from prospective cohort studies and clinical trials when available. Evidence from experimental
ReviewDietary factors and Alzheimer's disease
Section snippets
Risk factors for AD
Mutations in the amyloid-precursor-protein gene (APP) on chromosome 21, the presenilin-1 gene (PS1) on chromosome 14, and the presenilin-2 gene (PS2) on chromosome 1, cause autosomal dominant AD with onset as early as the third decade of life.13 An allelic variant of apolipoprotein-E (APOE), ε4, has also been associated with sporadic and familial disease with onset usually after age 65 years.14
No specific environmental risk factor has been definitively identified as being associated with AD.
Diet and AD
Animal models have shown that dietary restriction extends the lifespan of rodents30 and increases the resistance of neurons to degeneration.30 Oxidative stress, which can be modified by diet, increases with ageing and may be related to AD.30 These observations imply a potentially important role for diet in the causation and prevention of AD that has been the subject of extensive study and several reviews.31, 32, 33, 34 Our objective is to comprehensively and practically review data relating
Antioxidants
Reactive oxygen species are associated with neuronal damage in AD.42 The increased production and deposition of Aβ are early events in the disease and increase oxidative stress.42, 43 The deposition of Aβ reduces iron and copper concentrations in brain tissue, leading to the formation of hydrogen peroxide, oxidative stress, and neuronal damage.44 Whether the presence of reactive oxygen species related to neuronal damage in AD is a primary or secondary event is unknown. The possibility that the
Dietary fats
Intake of non-hydrogenated unsaturated fats, low intake of hydrogenated and saturated fats, and high intake of n-3 polyunsaturated fatty acids (PUFA) from fish or vegetable sources can lower the risk of cardiovascular disease86 and potentially lower the risk of AD through vascular mechanisms. Dietary fats may also influence AD through other mechanisms. Higher intake of hydrogenated and saturated fats are related to insulin resistance,87 and high insulin concentrations may be related to a high
Alcohol
Alcohol is a neurotoxin, and rat models show that different exposures to alcohol can result in oxidative brain damage.101 Intermittent exposures to intoxicating doses of alcohol can result in neuronal mitochondrial dysfunction and degeneration in rats.102 Moderate alcohol consumption in human beings is related to greater brain atrophy, but is also related to fewer silent brain infarcts, less white-matter disease,103 and is related to a lower risk of clinical stroke.104 Thus, alcohol may have
Caveats of the evidence relating diet and AD
One of the main limitations of studies of diet and disease is error in the measurement of nutrients.118 If the measurement error is not related to the outcome, it will result in underestimation of true associations. If the measurement error is different according to the outcome status, it can lead to underestimation or overestimation of the associations. The development of AD may be the consequence of lifelong exposures, or at least of exposures that begin in middle age or late adult life. The
Summary of recommendations
Most of the data relating diet and AD are from observational studies and are inconsistent. Thus, recommendations of dietary interventions specifically for the prevention of AD cannot be made at this time. However, some of the diets that may be beneficial for AD are beneficial for other disorders, such as cardiovascular disease, or are unlikely to be harmful, and some recommendations can be made on the basis of these characteristics. In the absence of trial data specifically addressing nutrients
Search strategy and selection criteria
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