No Benefit for DHA in Alzheimer's Disease

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Dietary supplementation with the omega-3 fatty acid "docosahexaenoic acid" (DHA) had no apparent benefit in slowing cognitive decline among patients with mild-to-moderate Alzheimer's disease, according to a large randomized trial.

The 18-month trial among more than 400 patients found that the rate of change -- measured on the cognitive subscale of the Alzheimer's Disease Assessment Scale -- actually increased 7.98 points among those given DHA, compared with 8.27 points among the placebo group, reported Dr. Joseph F. Quinn of Oregon Health and Science University in Portland and colleagues.

Moreover, there was no difference in the rate of change on the Clinical Dementia Rating -- which was an increase of 2.87 points for the DHA supplement group and 2.93 for those on placebo, Quinn and co-authors reported in the Nov. 3 issue of the Journal of the American Medical Association.

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Epidemiologic studies have found that consumption of fish rich in omega-3s and fish oil may help lower the risk of Alzheimer's disease, and animal studies have suggested that the DHA component of omega-3 fatty acids reduced some of the pathologic brain changes.

To assess the potential effects on dementia, Quinn's group enrolled 402 patients with mild-to-moderate disease and low DHA levels from 51 participating centers around the U.S., randomizing them to 2 g/day of DHA or to placebo.

A subset of patients underwent MRI at baseline and again at 18 months, and there was no difference between the groups on decline in total brain volume.

There also was no difference in percentage of brain volume decline, or in volume declines seen in the left or right regions of the hippocampus.

The investigators also considered whether there would be differences according to baseline dementia severity, and again found that the rate of change was similar.

There was, however, a difference in patients according to APOE e4 status, with those being negative for this allele having a smaller change in cognitive scores.

Some epidemiologic studies also suggested benefits of omega-3 fatty acids among APOE e4-negative patients, "so an APOE genotype-specific effect is plausible," Quinn and co-authors wrote.

Adverse events were similar in the two groups, with almost 90 percent of the DHA and placebo patients experiencing at least one adverse event.

Three patients on warfarin in the DHA group had decreases in the international normalized (INR) ratio for blood coagulation, while one placebo patient had an increase.

The investigators acknowledged a large number of study dropouts -- including 28 percent of the DHA group and 24 percent of the placebo group -- which they ascribed to a perceived lack of efficacy by the participants.

Despite the finding that even patients who were less impaired at baseline failed to benefit from DHA, the authors didn't rule out the possibility that DHA supplementation early in the course of decline might be protective.

"Individuals intermediate between healthy aging and dementia, such as those with mild cognitive impairment, might derive benefit from DHA supplementation, although further study will be necessary to test this hypothesis," Quinn and co-authors wrote.

In an accompanying JAMA editorial, Dr. Kristine Yaffe of the University of California San Francisco asked why -- despite all the recent advances in the scientific understanding of dementia -- there still are so few treatments.

"Because [Alzheimer's disease] is such a devastating illness and current therapeutic choices are limited and only moderately effective, new treatment options are urgently needed," Yaffe wrote.

New approaches that could be tried include combined regimens, as are often used in other chronic diseases, or combining medical with behavioral therapies, she suggested.