Diet and Alzheimer's Disease: What the Evidence Shows

Martha Clare Morris, ScD

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Fish and n-3 Fatty Acids

Long-chain n-3 fatty acids, a type of polyunsaturated fat consumed almost exclusively from fish, may also hold promise for the prevention of Alzheimer's disease. One of the n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), is the primary component of membrane phospholipids in the brain and is particularly abundant in the more metabolically active areas. DHA is directly available in fish, but smaller amounts can be synthesized endogenously from its precursor n-3 fatty acids, alpha-linolenic acid (18:3n-3) and eicosapentaenoic acid (EPA, 20:5n-3). EPA is also consumed directly from fish, but alpha-linolenic acid is obtained from vegetable oils and nuts.

The n-3 polyunsaturated fatty acids have antiaggregatory, antithrombotic, and anti-inflammatory properties. Much of the evidence of the neuroprotective effects of the n-3 fatty acids stems from investigations of their importance as essential dietary components in early brain development. In animal models, rodents fed diets enriched with n-3 fatty acids performed better in learning and memory tasks compared with rodents fed control diets.[24,25,26] A number of studies have found that the n-3 fatty acid diet resulted in better regulation of neuronal membrane excitability,[27] improved capacity for neuronal transmission,[28] and reduced oxidative damage.[29]

Several case-control studies reported lower biochemical levels of n-3 fatty acids in the plasma[30] and brain tissue[31] of patients with Alzheimer's disease compared with controls. One fish meal a week was associated with a 60% reduction in the risk of developing Alzheimer's disease in both the Rotterdam and Chicago studies.[9,32] The Chicago study also examined risk of disease according to intake of the n-3 fatty acids. Higher total intake of the n-3 fatty acids was significantly associated with a lower risk for Alzheimer's disease. DHA provided the strongest association, EPA was not associated, and alpha-linolenic acid was associated with lower risk only among persons with the APOE-ε4 allele. The Rotterdam study did not find an association between total intake of n-3 fatty acids and risk of Alzheimer's disease.[10]

Although these studies show promise that dietary intake of fish and n-3 fatty acids may protect against Alzheimer's disease, more research needs to be done before we can attribute the findings of these few studies to a causal association.

Thus far, no human study has indicated that taking a fish oil capsule is associated with less risk of developing the disease, although several clinical trials are currently in progress to examine the therapeutic effect in patients with Alzheimer's disease.

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