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Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial


Quinn, Joseph F., Raman, Rema, Thomas, Ronald G., Yurko-Mauro, Karin, Nelson, Edward B., van Dyck, Christopher, Galvin, James E., Emond, Jennifer, Jack, Clifford R., Jr., Weiner, Michael, Shinto, Lynne, Aisen, Paul S


JAMA, Volume: 304, No.: 17, Pages.: 1903-1911

Year of Publication



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.; 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 cm(3) (95% CI, 21.4-28.0 cm(3)) during 18 months and a 1.32% (95% CI, 1.14%-1.50%) volume decline per year compared with 24.0 cm(3) (95% CI, 20-28 cm(3)) 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: Identifier: NCT00440050.;

Bibtex Citation

@article{Quinn_2010, doi = {10.1001/jama.2010.1510}, url = {}, year = 2010, month = {nov}, publisher = {American Medical Association ({AMA})}, volume = {304}, number = {17}, pages = {1903}, author = {Joseph F. Quinn and Rema Raman and Ronald G. Thomas and Karin Yurko-Mauro and Edward B. Nelson and Christopher Van Dyck and James E. Galvin and Jennifer Emond and Clifford R. Jack and Michael Weiner and Lynne Shinto and Paul S. Aisen}, title = {Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease}, journal = {{JAMA}} }


acid, aged, aged, 80 and over, alzheimer disease, apolipoprotein e4, atrophy, brain, cognition disorders, complications, dietary supplements, disease progression, docosahexaenoic, docosahexaenoic acids, double-blind method, drug therapy, etiology, female, genetics, humans, magnetic resonance imaging, male, pathology, therapeutic use, treatment outcome

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions