ω-3 Ethyl ester results in better cognitive function at 12 and 30 months than control in cognitively healthy subjects with coronary artery disease: a secondary analysis of a randomized clinical trial

Abstract

Background Omega-3 (n–3) fatty acids have shown benefit in cognitively impaired subjects, but the effect on cognitively healthy older subjects is unclear. Objectives Our aim was to determine if long-term, high-dose ω-3 ethyl esters, EPA (20:5n–3) and DHA (22:6n–3), prevent deterioration of cognitive function in cognitively healthy older adults. Methods A total of 285 subjects with stable coronary artery disease (CAD) on statin treatment were randomly assigned to 3.36 g EPA and DHA or none (control) for 30 mo. Cognitive function was assessed in all 285 subjects at baseline and in 268 and 250 subjects who returned at 12- and 30-mo follow-up, respectively, with neuropsychological testing as a prespecified secondary outcome. A completer's analysis, along with a sensitivity analysis carrying forward the last observation, was performed. Results Over the 30-mo period, subjects randomly assigned to EPA and DHA had significantly better scores than control for verbal fluency, language, and memory (mean: 1.08; 95% CI: 0.25, 1.91; P = 0.011) and 2 tests of visual-motor coordination (mean: −2.95; 95% CI: −5.33, −0.57; P = 0.015 and mean: −9.44; 95% CI: −18.60, −0.30; P = 0.043, respectively). The better scores for EPA and DHA were due to an improvement at 12 mo compared with baseline in verbal fluency, language, and memory (P = 0.047) and 2 tests of visual-motor coordination (P = 0.033 and P < 0.001, respectively), whereas control had no change. Post hoc analyses indicated no difference by age, sex, or diabetes status. Conclusions Cognitively healthy older adults with stable CAD randomly assigned to high-dose EPA and DHA had improved cognitive function over a 30-mo period compared with control. These findings may be especially important for CAD patients because CAD is a risk factor for cognitive decline. This trial was registered at clinicaltrials.gov as NCT01624727.

Docosahexaenoic Acid Levels and Omega-3 Index, but Not Eicosapentaenoic Acid Levels, Are Associated With Improved Cognition in Cognitively Healthy Subjects With Coronary Artery Disease

“…No significant differences were observed in baseline characteristics in the EPA+DHA and control groups. 1 After adjustment for age, sex, body mass index, diabetes, hypertension, and statin use, the Figure [A] reports that subjects with DHA levels above the median (85 µg/mL) were associated with improvement in two cognitive function tests: controlled oral word association test 1, a measure of verbal fluency, language and memory, and TMT A, a test of visual-motor coordination whereas EPA levels were not associated. An omega-3 fatty acid index ≥ 4% had the strongest association for controlled oral word association test 1 and was also associated with significant improvement in the digit symbol substitution test, which measures psychomotor speed, sustained attention, response speed and visual-motor coordination, at both 12 and 30 months compared to baseline.…”

“…No significant differences were observed in baseline characteristics in the EPA+DHA and control groups. 1…”

Nutrition, Physical Activity, and Other Lifestyle Factors in the Prevention of Cognitive Decline and Dementia

“…There are also some sporadic positive results. For example, among 285 participants with stable coronary artery disease on statin treatment randomized to 3.36 g/d EPA and DHA or none for 30 months assessing cognitive function at baseline and after 12 and 30 months with neuropsychological testing, participants on EPA/DHA treatment had significantly better scores vs. controls for verbal fluency, language, recall memory, and visual-motor coordination [249]. A post doc analysis of the placebo-controlled trial Folic Acid and Carotid Intima-media Thickness (FACIT) investigated the interaction between baseline omega-3 PUFA statuses and folic acid treatment on cognitive decline in 791 older adults aged 50-70 years.…”

Omega-3 fatty acids and cognitive function

“…Of note, in a RCT of 390 individuals (mean age 73) randomized to 1720 mg of DHA and 600 mg of EPA over 18 months, apoE4 carriers improved significantly on reasoning ( P = 0.02) compared with placebo of 990 mg oleic acid. [50] See Malik et al [36 ▪ ] for descriptions of the other trials. In summary, of the 15 RCTs in cognitively healthy older adults, seven reported benefit on cognitive function measured by neuropsychological testing, whereas eight reported no benefit.…”