Abstract

BackgroundSome studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein.MethodsThe study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437

Highlights

  • Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults

  • All loadings were of at least moderate magnitude, significant, and in the expected direction and the model fit the data well (c2 = 66.42, df = 42, p = .010; Root Mean Square Error of Approximation (RMSEA) = .039, 90%CI [.019, .056]; Comparative Fit Index (CFI) = .984; Akaike Information Criterion (AIC) = 162.4); the covariance matrix among the factors was not positive definite because the correlation between Long-term Memory and Short-term Memory was near unity (r = .975)

  • To examine whether both factors were necessary, a model was specified without Long-term Memory and with the delayed memory tasks loading on Short-term Memory (c2 = 71.5, df = 46, p = .009; RMSEA = .038, 90%CI [.019, .054]; CFI = .983; AIC = 159.5)

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Summary

Introduction

Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. Only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations still remain unclear. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are one diet-related factor suggested to influence cognitive decline during ageing. Evidence from animal studies supports this; animals fed a low n-3 PUFA diet show cognitive deficits [4,5] that are ameliorated by DHA supplementation [6,7] and DHA supplementation improves memory performance in aged mice [8]

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