In the most recent round of science to evaluate DHA and cognitive function, the omega 3 fatty acid failed to benefit those with mild to moderate Alzheimer’s disease, but another trial showed some benefit to healthy subjects.

Results from these two large studies, which both used algal DHA from Martek Biosciences, Columbia, MD, were reported at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna.

The Alzheimer’s Disease Cooperative Study (ADCS)—funded by the National Institute on Aging (NIA)—was a double blind, randomized, placebo-controlled clinical trial that compared DHA and placebo in 402 people (average age=76) diagnosed with mild to moderate Alzheimer’s at 51 sites in the U.S. over an 18-month period.

The other study, conducted by Martek, lasted 6 months, and tested DHA in healthy people to evaluate its effect on “age related cognitive decline.”

The results of the ADCS trial show no evidence for benefit in the studied population, according to researchers. The Martek trial showed a positive result on one test of memory and learning in healthy older adults, not people with Alzheimer’s or another dementia.

“These two studies—and other recent Alzheimer’s therapy trials—raise the possibility that treatments for Alzheimer’s must be given very early in the disease for them to be truly effective,” said William Thies, PhD, chief medical & scientific officer at the Alzheimer’s Association. “For that to happen, we need to get much better at early detection and diagnosis of Alzheimer’s, in order to test therapies at earlier stages of the disease and enable earlier intervention.”

At the beginning of the ADCS trial, all participants had a dietary DHA intake of less than 200 mg per day. Subjects were treated with DHA or placebo at a dose of two grams per day for 18 months. Those participants already taking approved Alzheimer’s drugs could continue taking them during the trial. Co-primary outcomes were rate of change on the Alzheimer’s disease assessment scale-cognitive (ADAS-cog) and rate of change on Clinical Dementia Scale-sum of the boxes (CDR-SOB). These two measures are the current standard tests used by FDA when assessing new Alzheimer’s drugs.

According to researchers, treatment with DHA clearly increased blood levels of DHA, and also appeared to increase brain DHA levels, based on a measured increase of DHA in study participants’ cerebrospinal fluid (CSF). However, DHA treatment did not slow the rate of change on tests of mental function (ADAS-cog), global dementia severity status (CDR-SOB), activities of daily living (ADL) or behavioral symptoms in the study population as a whole. There was no different treatment effect between the mild and moderate Alzheimer’s patients.

“These trial results do not support the routine use of DHA for patients with Alzheimer’s,” said Joseph Quinn, MD, Associate Professor of Neurology at Oregon Health and Sciences University and a lead study author.

In a pre-planned exploratory data analysis, study participants were divided according to whether or not they carried the “e4” version of the “ApoE” gene. ApoE-e4 increases the risk of developing Alzheimer’s but does not appear to modify the rate of disease progression. In the people who had an ApoE-e4 gene, the researchers found no benefits of DHA treatment. In contrast, those without the ApoE-e4 gene who received DHA had a slower rate of decline on the primary test of mental function (the ADAS-cog). A trend in the same direction was seen on the Mini-mental state examination, another test of mental function.

“This is an intriguing exploratory result,” said Dr. Quinn. “However it must be treated with appropriate caution. The finding requires further study for confirmation.”

Researchers at Martek examined the effects of algal DHA as a possible neuroprotective nutritional supplement for age-related cognitive decline in their Memory Improvement with DHA Study (MIDAS).

Scientists led by Karin Yurko-Mauro, PhD, Associate Director of Clinical Research at Martek, conducted a randomized, double-blind, placebo-controlled, multi-center, 6-month study to determine the effects of 900 mg per day of algal DHA on improving cognitive functions in 485 healthy older people (average age=70) with mild memory complaint. The primary outcome measure was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial episodic memory test.

After six months, the researchers found that the study participants taking DHA supplements made significantly fewer errors on the PAL compared to when they started the study (-1.63 ± 0.76, p<0.03). Plasma phospholipid DHA levels doubled over the course of the study in those people taking the supplements, and correlated with the PAL response (p<0.04).

They also observed a significant decrease in heart rate in those taking DHA (change from baseline of -3.2 vs. -1 BPM, p<0.03) that was highly correlated with week 24 plasma levels (p<0.01). Blood pressure and body weight remained unchanged between groups. Plasma levels of Alzheimer's related proteins Abeta 1-40, 1-42 and hs-CRP were not significantly different.

“In our study, healthy people with memory complaints who took algal DHA capsules for six months had almost double the reduction in errors on a test that measures learning and memory performance versus those who took a placebo,” Dr. Yurko-Mauro said. “The benefit is roughly equivalent to having the learning and memory skills of someone three years younger.”