van de Rest O et al. (2008) Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 71: 430–438

Virtanen JK et al. (2008) Fish consumption and risk of subclinical brain abnormalities on MRI in older adults. Neurology 71: 439–446

The ω-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to influence features of neural function, including neurotransmission, membrane fluidity, and regulation of enzymes and ion channels. In theory, increased intake of EPA and DHA, through dietary supplementation or consumption of fatty fish, could alleviate cognitive decline in older adults, but results from previous studies have been inconsistent. Two new studies published in Neurology demonstrate that increased levels of these fatty acids do not necessarily affect cognitive performance, but that they might prevent subclinical brain abnormalities.

In van de Rest et al.'s double-blind, controlled trial, 302 cognitively intact, older individuals (age >65 years, Mini Mental State Examination score >23) in The Netherlands were randomly allocated to receive a daily dose of 1,800 mg combined EPA and DHA, 400 mg EPA and DHA, or placebo. The recommended daily intake of these fatty acids in The Netherlands is 450 mg. Participants were assessed by a battery of cognitive tests at baseline and at 13 and 26 weeks after treatment allocation. In general, cognitive test scores improved in all groups at both follow-up assessments—all three groups improved to the same extent. However, in the subset of individuals who were carrying the APOE ε4 allele—which has been linked to age-related memory disorders—supplementation with fish oil was associated with significantly improved scores in the attention domain (P = 0.04 and P = 0.03, respectively, for comparisons of high-dose and low-dose groups with the placebo group).

Virtanen and colleagues assessed whether the frequency of fish consumption affects the development of subclinical brain abnormalities in individuals aged ≥65 years. Those who ate tuna or other baked or broiled fish (which contain high amounts of EPA and DHA) at least three times per week had a decreased risk of prevalent subclinical infarct compared with those who ate such fish less than one time per month (relative risk 0.74; Ptrend = 0.03). Each additional serving of fish consumed per week was associated with a 7% decrease in the relative risk of prevalent subclinical infarct (P = 0.03). Increased consumption of baked or broiled fish was also associated with improved white matter grade (P = 0.003), but not with sulcal and ventricular grades, which are indicators of brain atrophy. A high intake of dietary EPA and DHA was similarly associated with a decreased risk of subclinical infarct and improved white matter grade.

The causal mechanisms that underlie the effects of polyunsaturated fatty acids on the brain are not yet understood. Virtanen et al. suggest that EPA and DHA might influence mechanisms related to small-vessel disease and thereby decrease subclinical brain abnormalities. In this regard, van de Rest et al. note that both short-term and long-term mechanisms might mediate this association and that further studies should be conducted to investigate the long-term effects of high EPA and DHA intake.