Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease

Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease
A Randomized Trial
Joseph F. Quinn, MD; Rema Raman, PhD; Ronald G. Thomas, PhD; Karin Yurko-Mauro, PhD; Edward B. Nelson, MD; Christopher Van Dyck, MD; James E. Galvin, MD; Jennifer Emond, MS; Clifford R. Jack Jr, MD; Michael Weiner, MD; Lynne Shinto, ND; Paul S. Aisen, MD
JAMA. 2010;304(17):1903-1911. doi:10.1001/jama.2010.1510
Context  Docosahexaenoic acid (DHA) is the most abundant long-chain polyunsaturated fatty acid in the brain. Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease. Animal studies demonstrate that oral intake of DHA reduces Alzheimer-like brain pathology.
Author Affiliations: Department of Neurology, Oregon Health and Science University, Portland (Drs Quinn and Shinto); Department of Neurosciences, University of California, San Diego (Drs Raman, Thomas, and Aisen, and Ms Emond); Martek Biosciences, Columbia, Maryland (Drs Yurko-Mauro and Nelson); Department of Psychiatry, Yale University, New Haven, Connecticut (Dr Van Dyck); Department of Neurology, School of Medicine, New York University, New York (Dr Galvin); Mayo Clinic, Rochester, Minnesota (Dr Jack); and Department of Radiology, University of California, San Francisco (Dr Weiner).
Objective  To determine if supplementation with DHA slows cognitive and functional decline in individuals with Alzheimer disease.
Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial of DHA supplementation in individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination scores, 14-26) was conducted between November 2007 and May 2009 at 51 US clinical research sites of the Alzheimer’s Disease Cooperative Study.
Intervention  Participants were randomly assigned to algal DHA at a dose of 2 g/d or to identical placebo (60% were assigned to DHA and 40% were assigned to placebo). Duration of treatment was 18 months.
Main Outcome Measures  Change in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and change in the Clinical Dementia Rating (CDR) sum of boxes. Rate of brain atrophy was also determined by volumetric magnetic resonance imaging in a subsample of participants (n = 102).
Results  A total of 402 individuals were randomized and a total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). Supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, which increased by a mean of 7.98 points (95% confidence interval [CI], 6.51-9.45 points) for the DHA group during 18 months vs 8.27 points (95% CI, 6.72-9.82 points) for the placebo group (linear mixed-effects model: P = .41). The CDR sum of boxes score increased by 2.87 points (95% CI, 2.44-3.30 points) for the DHA group during 18 months compared with 2.93 points (95% CI, 2.44-3.42 points) for the placebo group (linear mixed-effects model: P = .68). In the subpopulation of participants (DHA: 53; placebo: 49), the rate of brain atrophy was not affected by treatment with DHA. Individuals in the DHA group had a mean decline in total brain volume of 24.7 cm³ (95% CI, 21.4-28.0 cm³) during 18 months and a 1.32% (95% CI, 1.14%-1.50%) volume decline per year compared with 24.0 cm³ (95% CI, 20-28 cm³) for the placebo group during 18 months and a 1.29% (95% CI, 1.07%-1.51%) volume decline per year (P = .79).
Conclusion  Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease.
Trial Registration  clinicaltrials.gov Identifier: NCT00440050