Omega-3 fatty acids

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Introduction

Several lines of reasoning have led to the hypothesis that consumption of some, or any omega-3 fatty acids (DHA and EPA, found primarily in fish, and ALA, found in plants) will reduce the risk of dementia and can even improve cognition in youth and in those with cognitive decline when combined with other strategies. The evidence, however, has been mixed. Until recently, the effects on ApoE-ε4 carriers has appeared to be weak to non-existent.

Effectiveness

Supplemental DHA is probably somewhat helpful as a preventive measure for ε4(-). Until recently, the effect was thought not to apply to ε4+. Once Alzheimer's has been diagnosed, fish oil alone seems likely ineffective regardless of ε4 status. Other omega-3 fatty acids are not as well researched.

A recent paper, however, concluded the following:

Conclusions and Relevance. In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology. [1]

Note, a few researchers suspect that the reason DHA has not been effective in providing cognitive benefit to ε4 carriers is that the negative consequences of DHA consumption (DHA oxidation) overwhelm potential benefits, and that consumption of sufficient antioxidants along with the DHA, or, alternatively, consuming it in a natural form, where it would be less subject to oxidation, would permit it to be beneficial for ε4 carriers. For a summary, see "Omega-3s, ApoE Genotype and Cognitive Decline". This theory has not been tested however, and the epidemiological evidence offered in support of the theory is mostly from societies that consume the omega-3 fatty acid found in plant-based diets, ALA (which, itself, may help ε4 carriers, but more research is needed). Indeed, recent evidence has demonstrated an alternative explanation for the differential effects of Omega-3s in ε4+ individuals via disrupted fatty acid metabolism. This paper, "Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Is It Contributing to Higher Risk of Cognitive Decline and Coronary Heart Disease?" demonstrates that ε4 carriers preferentially metabolize Omega-3s suggesting this population may actually need higher levels. (As you read, bear in mind that β-oxidation is NOT the same as lipid peroxidation. β-oxidation (beta-oxidation) is the catabolic process in which fatty acids are used by the body as a source of energy. Lipid peroxidation refers to the oxidative degradation of lipids.)

This study Anterior cingulate cortex mediates the relationship between O3PUFAs and executive functions in APOE e4 carriers is groundbreaking in that it examined Omega-3 levels in an exclusively ε4+ data set. Rather than comparing theε4+ population to the general population (which typically results in ε4 carriers demonstrating no benefit) researchers compared HIGH Omega-3 levels (mean: 216.00 nmol/mL) vs. LOW Omega-3 levels (mean: 102.30 nmol/mL) among ε4 carriers using both cognitive testing and brain imaging. These older adults at risk of late-onset Alzheimer's disease, who consumed more Omega-3 fatty acids did better than their peers on tests of cognitive flexibility, the ability to efficiently switch between tasks, and had a bigger anterior cingulate cortex, a brain region known to contribute to cognitive flexibility.

Other researchers, concerned that the levels of mercury in fish could negate any potential neuroprotective benefits, tested that theory in their paper Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults. Tthey did find that eating a moderate amount of seafood was tied to higher levels of mercury in the brain, but these higher levels weren't associated with more Alzheimer's neurology. Interestingly, the cognitive benefits of having one seafood meal per week was ONLY found in ε4+ individuals on multiple measures of Alzheimer's disease.

• Lower density of neuritic plaques (β= -0.69 score units)
• Less severe and widespread neurofibrillary tangles (β= -0.77 score units)
• Lower neuropathologically defined Alzheimer's disease (β= -0.53 score units)