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Release Date: October 23, 2006; Valid for credit through October 23,
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October 23, 2006 — Omega-3 fatty acid supplements may slow cognitive decline in patients with very mild Alzheimer's disease (AD), a study published in the October 2006 issue of the Archives of Neurology suggests.
The randomized, double-blind, placebo-controlled trial of 174 AD patients found overall administration of omega-3 fatty acids made no difference to the rate of cognitive decline compared with placebo at 6-months follow-up. However, a small subgroup of 32 patients with mild AD experienced a significant reduction in their rate of cognitive decline compared with the placebo group.
"Notwithstanding the negative results in the entire group of patients, our study indicated that the omega-3 fatty acid preparation conferred a slower decline of cognition in those with the mildest impairment compared with placebo-treated control subjects with a similar degree of cognitive dysfunction at the start of the study," the authors write.
Led by Yvonne Freund-Levi, MD, from the Karolinska Institute in Stockholm, Sweden, the study was conducted between December 31, 2000, and March 24, 2004.
Inclusion criteria consisted of a diagnosis of AD and a Mini-Mental State Examination (MMSE) score between 15 and 30 points. In addition, patients had to receive a stable dose of acetylcholine esterase inhibitors for at least 3 months prior to the start of the study. All subjects lived in their own home and planned to continue acetylcholine esterase inhibitors for the duration of the study.
Patients were excluded if they were treated with nonsteroidal anti-inflammatory agents, omega-3 preparations, or anticoagulants. In addition, subjects who abused alcohol, had a concomitant serious illness, or who did not have a caregiver were also excluded from the trial.
Routine blood and urine analyses, blood pressure assessment, global function using the Clinical Dementia Rating Scale, and cognitive function using the MMSE and the modified cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-COG) were evaluated at baseline and again at 6 and 12 months.
Subjects were randomized to receive a daily dose of four 1-g tablets, containing a combination of 430 mg of docosahexaenoic acid (DHA) and 150 mg of eicosapentaenoic acid (EPA) or placebo. However, after 6 months, subjects in the placebo group were also given supplements.
According to the current authors, in many previous trials of supplementation with omega-3 fatty acids, EPA has been the predominant acid over DHA. However, in the current study, there was 2.8 times more DHA than EPA. The rationale for this, the current authors explain, is based on previous research that has shown AD-affected brains are deficient in DHA. Furthermore, studies in transgenic mouse models of AD have shown that dietary DHA reduced total amyloid in the brain in a dose-dependent way, particularly in the hippocampi and parietal cortices.
"These areas are also the earliest to be affected by AD in human beings, disturbing for example, verbal episodic memory. The neuropathologic findings in this mouse model of AD may mimic a very early stage of AD," the authors write.
The study's primary outcomes included cognitive function testing assessed by MMSE and ADAS-COG. Secondary outcomes were safety, tolerability, blood pressure, and global function as assessed by the Clinical Dementia Rating Scale.
At 6 months, there was no difference in the rate of cognitive decline between the 2 groups. However, among a subgroup of 32 patients with very mild cognitive impairment at the beginning of the study, those who took omega-3 supplements experienced less decline at 6 months vs the placebo group.
In addition, the authors note that at 12-month follow-up of patients who were initially in the placebo group also demonstrated a slowed rate of cognitive decline once they began taking omega-3 supplements.
According to the investigators, the mechanisms by which omega-3 fatty acids interfere in AD pathology are not clear. However, they speculate that fish oil's anti-inflammatory effects may play a role in the early, but not later, stages of the disease.
"It is possible that when the disease is clinically apparent, the neuropathologic involvement is too advanced to be substantially attenuated by anti-inflammatory treatment," the researchers write.
The authors caution that the study's finding should not serve as a basis for general recommendations for the treatment of AD with fish oil preparations. However, they note, such supplements should be tested in larger cohorts with mild cognitive impairment to determine whether omega-3 fatty acids could potentially halt initial progression of AD.
Arch Neurol. 2006;63:1402-1408.