Patients with mild-to-moderate forms of Alzheimer disease did not experience improvements in cognitive and functional decline after receiving omega-3 fatty docosahexaenoic acid supplements, according to findings published today in the Journal of the American Medical Association.

The research, part of a special JAMA issue on aging, disproves earlier circumstantial evidence from observational studies suggesting that fish oil might be able to reverse the effects of Alzheimer disease.

“DHA supplementation did not slow the rate of progression to Alzheimer disease,” Joseph F. Quinn, MD, study researcher and associate professor of Neurology at Oregon Health and Science University, in Portland, said during a press conference in Washington, D.C., this morning.

Quinn and colleagues from the Alzheimer Disease Cooperative Study, a consortium of investigators funded by the National Institute of Aging, enrolled 405 patients with mild-to-moderate Alzheimer disease at 51 U.S. research sites, between November 2007 and May 2009.

The researchers randomly assigned participants to a daily 2g dose of docosahexaenoic acid (DHA) or placebo for 18 months, and assessed changes in cognitive and functional abilities using the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Clinical Dementia Rating (CDR) sum of boxes.

Among the 295 patients who completed the trial, they found that scores on both tests were similar in both the DHA and placebo groups (ADAS-cog: 7.98 DHA vs. 8.27 placebo; CDR: 2.87 DHA vs. 2.93 placebo).

Similarly, DHA seemed to have no effect on brain tissue loss in a subset of patients who underwent magnetic resonance imaging to measure total brain volume at baseline and follow-up (DHA group: 53; placebo group: 49) – a very concrete measure of disease progression, according to Quinn.

“Unfortunately on all the clinical outcome measures, we failed to see evidence of clinical benefit of DHA supplementation,” Quinn said.

Despite these findings, Quinn suggested that the protective effects of fish oil cannot yet be ruled out.

He explained that previous animal studies have shown that amyloid plaque loss – a pathologic change that occurs in the brain of patients with Alzheimer disease – may take place long before neurodegenerative symptoms are detected.

The patients in the study – those who have already received diagnoses of mild-to-moderate disease progression – may have already experienced this irreversible change, rendering the DHA supplements ineffective. “If amyloid plaque is the target, the intervention really needs to start very early,” he said.

Furthermore, a subanalysis of patients who participated in the current study revealed that a genetic component – the presence of apiloprotein genotype e4 – may make certain patients less susceptible to the benefits of omega-3 fatty acids.

Quinn emphasized that no data from the current trial offer adequate support of either hypothesis, but that both theories are plausible and require follow up.

“Alzheimer disease is the sixth largest cause of death in the United States. For every dollar spent in care, less than a penny is spent in research,” said Margaret Winker, MD, co-editor of the JAMA Aging issue, emphasizing the study’s importance.