Abstract

Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction. The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults. In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA+400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined. Compared with placebo, fish oil improved CVR to a processing speed test (4.4%±1.9% vs. -2.2%±2.1%; P=0.023) and processing speed in males only (Z-score: 0.6±0.2 vs. 0.1±0.2; P=0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P=0.006) and C-reactive protein (R = -0.183, P=0.046). Curcumin improved CVR in a working memory test (3.6%±1.2% vs. -0.2%±0.2%, P=0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2±0.1 vs. -0.5±0.2, P=0.039). Combining fish oil with curcumin did not produce additional benefits. Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p.

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