DHA Levels in the Brain Tied to Cognitive Function in APOE4 Carriers

High-dose supplements of docosahexaenoic acid (DHA), an omega-3 fatty acid, showed no effect on hippocampal volume or cognition, according to findings from the placebo-controlled PreventE4 trial presented at the Clinical Trials on Alzheimer’s Disease conference in Madrid. However, increases in brain DHA in both the treatment and placebo arms were associated with better cognitive measures.

In this exclusive MedPage Today video, researcher Hussein Yassine, MD, of the Keck School of Medicine at the University of Southern California in Los Angeles, discusses the study results.

Following is a transcript of his remarks:

Basically we conducted a trial, we called it PreventE4. The trial took about 8 years to finish. The question that we were asking is whether higher doses of omega-3s, specifically DHA [docosahexaenoic acid], can have a role in the prevention of or slowing down the process of dementia.

The primary outcome of the trial is how much of this omega-3 is getting into the brain. The secondary outcome included the volume of the hippocampus, which is the memory area of the brain, and the exploratory outcome included cognition.

So basically, the background is that we have done studies indicating that E4 [APOE4] carriers — and E4 is a strong genetic risk factor for dementia — might need more omega-3s based on some elegant imaging studies and basic science studies we have done. And there’s also epidemiology studies and some other trials that suggested a signal. We found that omega-3s when given to E4 carriers before the onset of dementia can get into the brain adequately, similar to people who don’t carry the APOE4 allele.

However, we found no statistical effect of these omega-3 treatments on either the hippocampal volume or cognition, meaning that whether you are taking the supplement or on placebo over the course of 2 years, there was no difference on your hippocampal volume or cognition.

However, the study had an interesting finding that I think is worth discussing. In the brain or cerebrospinal fluid, the greater the amount of omega-3s, the better the cognitive function. And that did not differ between those on placebo or those on supplements, which means that omega-3s are important. But taking it from a supplement or from a different source doesn’t really make a difference. Getting more omega-3s into your brain, whether it’s a diet or a lifestyle change or exercise, might be as good as taking it in a supplement. And the more of it in the brain, the better people perform on cognition.

And interestingly, this relationship was only seen in those who have E4, not on those who don’t have this genetic risk factor.

So basically, in summary, supplementation did not really work in this trial, but it seems like omega-3s are good for the brain and getting them into the brain is going to be the next step. Figuring out how to get them in the brain is going to be our next frontier.

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