TY - JOUR
T1 - Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease
T2 - A randomized trial
AU - Quinn, Joseph F.
AU - Raman, Rema
AU - Thomas, Ronald G.
AU - Yurko-Mauro, Karin
AU - Nelson, Edward B.
AU - Van Dyck, Christopher
AU - Galvin, James E.
AU - Emond, Jennifer
AU - Jack, Clifford R.
AU - Weiner, Michael
AU - Shinto, Lynne
AU - Aisen, Paul S.
PY - 2010/11/3
Y1 - 2010/11/3
N2 - 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 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 cm 3 (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.
AB - 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 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 cm 3 (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.
UR - http://www.scopus.com/inward/record.url?scp=78049407029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78049407029&partnerID=8YFLogxK
U2 - 10.1001/jama.2010.1510
DO - 10.1001/jama.2010.1510
M3 - Article
C2 - 21045096
AN - SCOPUS:78049407029
SN - 0098-7484
VL - 304
SP - 1903
EP - 1911
JO - JAMA
JF - JAMA
IS - 17
ER -