The results of an 18 month trial conducted by the Alzheimer's Disease Cooperative Study (ADCS) showed no evidence for benefit of DHA, an omega 3 fatty acid, in people with mild to moderate Alzheimer's.

Another trial showed DHA to be effective on one test of memory and learning, but that study was in healthy older adults, not people with Alzheimer's or another dementia. The results need confirmation, as is standard scientific practice.

"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, 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."

DHA (docosahexaenoic acid) is naturally found in the body in small amounts, and is the most abundant omega 3 fatty acid in the brain. DHA oil is abundant in some marine microalgae, which provide the DHA that makes fatty fish a good source of DHA. Dietary DHA is also available in foods enriched with algal DHA or fish oils, and dietary supplements. Previous animal studies and epidemiology in humans suggested that DHA may be beneficial in people with Alzheimer's.

In the first study researchers conducted a double blind, randomized, placebo-controlled clinical trial comparing DHA and placebo in 402 people (average age=76) diagnosed with mild to moderate Alzheimer's at 51 sites in the U.S.

At the beginning of the 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 the 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 (NPI) in the study population as a whole. There was no different treatment effect between the mild and moderate Alzheimer's patients.

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.

"One of the issues raised by this study, and other recent Alzheimer's and mild cognitive impairment therapy trials, concerns a possible interaction between certain therapies and genetic status. This issue needs to be explored more completely in future trials."

In the second study, scientists led by Karin Yurko-Mauro conducted a randomized, double-blind, placebo-controlled, multi-center, six 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.

The researchers observed no treatment-related serious adverse effects in the study, and the adverse effects profile for DHA was the same as for the placebo.

"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," Yurko-Mauro said. "The benefit is roughly equivalent to having the learning and memory skills of someone three years younger."
References:
1. Joseph Quinn, et al. A clinical trial of docosahexaenoic acid (DHA) for the treatment of Alzheimer's disease. Alzheimer's Association.
2. Karin Yurko-Mauro, et al. Results of the MIDAS Trial: Effects of Docosahexaenoic Acid on Physiological and Safety Parameters in Age-Related Cognitive Decline. Alzheimer's Association.