AD Patients Not Helped By Fish Oil Ingredient, Study Reports

Neurology Today
18 November 2010; Volume 10(22); p 9, 12, 13

Fitzgerald, Susan

Investigators reported that patients who were given the omega-3 fatty acid docosahexaenoic acid fared no better cognitively or functionally than those who took a placebo over 18 months.

THE QUESTION of whether DHA or fish oil in general could be a preventive agent for those at risk for developing Alzheimer disease remains on the table.

[ Click here to enlarge ]

A key ingredient found in fish oil did nothing to slow the decline of patients with mild to moderate Alzheimer disease (AD), according to a Nov. 3 study in the Journal of the American Medical Association (JAMA). Patients who were given the omega-3 fatty acid docosahexaenoic acid (DHA) fared no better cognitively or functionally than those who took a placebo over 18 months.

Previous studies have suggested that DHA might prove to be a useful tool in slowing the advance of Alzheimer disease (AD), but this study seems to put that idea to rest, at least for now. Researchers said the question of whether DHA or fish oil in general could be a preventive agent for those at risk for developing AD remains on the table.

“These results indicate that DHA supplementation is not useful for the population of individuals with mild to moderate Alzheimer disease,” the researchers concluded.

The study's lead author, Joseph F. Quinn, MD, associate professor of neurology at Oregon Health and Science University and a physician at the Portland VA Medical Center, told Neurology Today that while he could understand why patients might think it's harmless to add supplements to their regimen, “we can't get in the position of recommending them in the absence of evidence.”

Dr. Quinn and other researchers said they'd like to see an equally rigorous study conducted to examine the use of DHA for the prevention of AD, but conceded that such a study would be difficult to carry out because it would have to involve a large number of carefully selected people over a longer period of time.

This latest study, funded by the National Institute on Aging, was carried out at 51 sites around the US from November 2007 to May 2009. The 402 participants were randomly assigned to receive either DHA at a dose of 2 grams a day or an identical placebo.

“Several studies have found that consumption of fish, the primary dietary source of omega-3 fatty acids, is associated with a reduced risk of cognitive decline or dementia,” the researchers wrote in the JAMA report. “Some studies have found that consumption of DHA, but not other omega-3 fatty acids, is associated with a reduced risk of Alzheimer disease.”

Patients qualified for the study if their Mini-Mental State Examination (MMSE) score was between 14 and 26; were medically stable; did not already consume a diet high in DHA; and were not taking DHA or omega-3 fatty acid supplements. People were excluded from the study if they took drugs with central anticholinergic effects or sedatives, or were receiving an investigational treatment for AD. Patients taking cholinesterase inhibitors or memantine were allowed to participate. Participants were on average 76 years old, and 52 percent of them were female.

DR. DAVID S. KNOPMAN said conducting a prevention study would be conceptually, financially and ethically difficult because “it would require identifying asymptomatic people at risk, which is challenging to do.”

[ Click here to enlarge ]

The study had two primary outcome measures: The rate of change over 18 months on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), as well as change on the Clinical Dementia Rating (CDR) sum of boxes. The ADAS-cog is a 70-point scale used to assess memory, attention, language, orientation and praxis, with higher scores indicating more impairment. The CDR sum of boxes is used to measure memory, orientation, judgment, and problem solving, community affairs, home and hobbies and personal care, according to the study report.

Assessments were done at baseline, 6 months, 12 months and 18 months. Of the 402 original participants, 295 finished the study. Dr. Quinn said the drop-out rate did not affect the validity of the findings, and noted that it is not uncommon for people to drop out of studies when they don't see the benefit they were hoping for.

DR. JOSEPH F. QUINN said that while he could understand why patients might think it's harmless to add supplements to their regimen, “we can't get in the position of recommending them in the absence of evidence.”

[ Click here to enlarge ]

The researchers found no difference in the rate of change on the two assessment scales for those taking DHA compared to the placebo. The DHA group's score on the ADAS-cog increased on average 7.98 points over 18 months, compared to an average increase of 8.27 points for the placebo group. The CDR sum of boxes score increased by 2.87 points for the DHA group over the length of the study, compared to 2.93 points for those taking the placebo.

The researchers also looked at brain atrophy in 102 study participants by conducting MRIs at baseline and 18 months.

“In the subgroup of participants with paired MRI scans, DHA had no effect on change in volume of hippocampus, whole brain, or ventricles,” the researchers reported.

The researchers did find some indication of a benefit of DHA, by measure of ADAS-cog and MMSE scores, in patients who tested negative for the apolipoprotein E4 (APOE4) gene. Dr. Quinn said that finding warranted a closer look.

Nikolaos Scarmeas, MD, associate professor of neurology at Columbia University Medical Center, told Neurology Today that the study results seem to settle the question of whether DHA could play a role in treating patients who already have a diagnosis of AD.

“I think the size and quality of this study, along with the previous ones in the literature, are more than enough to conclude that there is no place for fish oil/DHA in the treatment of Alzheimer disease,” Dr. Scarmeas noted. “Regarding Alzheimer disease prevention, the landscape is not as clear. There is potential room for further research.”

The research team noted in its JAMA report that because “part of the rationale for the trial was epidemiological evidence that DHA use before disease onset modifies the risk of Alzheimer disease, it remains possible that an intervention with DHA might be more effective if initiated earlier in the course of the disease in patients who do not have overt dementia”

David S. Knopman, MD, professor of neurology at the Mayo Clinic who was part of the research group that conducted the DHA study, likewise told Neurology Today that while the study found no payoff for using DHA in treating patients who already have cognitive impairment, “it does not mean it might not have a protective effect” for those who don't yet show symptoms. “That said, there is no evidence that DHA has benefits in asymptomatic people at risk for Alzheimer disease, Dr. Knopman said. He said conducting a prevention study would be conceptually, financially, and ethically difficult because “it would require identifying asymptomatic people at risk, which is challenging to do.”

DR. NIKOLAOS SCARMEAS: “I think the size and quality of this study, along with the previous ones in the literature, are more than enough to conclude that there is no place for fish oil/DHA in the treatment of Alzheimer disease.”

[ Click here to enlarge ]

Dr. Scarmeas said that while these latest study results are disappointing, they are useful. “DHA/fish oil is very commonly taken by Alzheimer patients. This is based on very thin evidence of its efficacy and is also a significant source of an additional financial burden for patients and families, and at the same time a source of income for companies producing these product and corresponding stores marketing them,” he noted. “The solid knowledge of lack of efficacy of DHA that is provided by the study in discussion is very important.”

Much of the excitement over the potential of fish oil/DHA stems from the observation that people who follow a Mediterranean-style diet appear to be at lower risk for Alzheimer disease. But the potential payoff of the Mediterranean diet has not been tested in a randomized clinical trial, Dr. Scarmeas said.

“An essential component of a Mediterranean-like diet is fish but it is not the only one,” he said. “In other words, it is not clear whether the potentially protective effects of the Mediterranean-like diet come from fish or fruits or vegetables or wine or olive oil or the low consumption of meats, etc. Interactions are also possible. Omega-3 fatty acids contained in fish could be biologically important only in the setting of consumption of other beneficial foods or avoidance of detrimental ones.”