title: Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.
abstract: OBJECTIVE
  Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.
  
  
  OBJECTIVE
  To test the effects of oral supplementation with nutrients on cognitive function.
  
  
  METHODS
  In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.
  
  
  METHODS
  Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.
  
  
  METHODS
  The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function.
  
  
  RESULTS
  A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant.
  
  
  CONCLUSIONS
  Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00345176.
authors: Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland.
authors: Emily Y
authors: EY
authors: Chew
authors: The EMMES Corporation, Rockville, Maryland.
authors: Traci E
authors: TE
authors: Clemons
authors: Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland.
authors: Elvira
authors: E
authors: Agrón
authors: Neuroepidemiology Section, National Institute on Aging/National Institutes of Health, Bethesda, Maryland.
authors: Lenore J
authors: LJ
authors: Launer
authors: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts5Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors: Francine
authors: F
authors: Grodstein
authors: Moran Eye Center, University of Utah, Salt Lake City.
authors: Paul S
authors: PS
authors: Bernstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001205:Ascorbic Acid / Q000008:administration & dosage; D003071:Cognition; D003300:Copper / Q000008:administration & dosage; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D059012:Lost to Follow-Up; D014975:Lutein / Q000008:administration & dosage*; D008268:Macular Degeneration / Q000208:ethnology / Q000628:therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D044469:Racial Groups; D013997:Time Factors; D014815:Vitamins / Q000008:administration & dosage*; D065146:Zeaxanthins / Q000008:administration & dosage*; D015034:Zinc Oxide / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: D015525:Fatty Acids, Omega-3; D014815:Vitamins; D065146:Zeaxanthins; D019207:beta Carotene; D004281:Docosahexaenoic Acids; D003300:Copper; D015118:Eicosapentaenoic Acid; D001205:Ascorbic Acid; D015034:Zinc Oxide; C030973:cupric oxide; D014975:Lutein