Results of the MIDAS trial: Effects of docosahexaenoic acid on physiological and safety parameters in age-related cognitive decline

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Background: Docosahexaenoic acid, (DHA), the principle omega-3 fatty acid in brain, plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Alzheimer's patients. Higher DHA intake and plasma levels are inversely correlated with relative risk of Alzheimer's disease (AD). Diet supplementation with Martek algal DHA oil reduces Aβ and tau levels in transgenic AD mouse models. Based on this collective data, we examined the effects of DHA clinically as a nutritional neuroprotective supplement for age-related cognitive decline (ARCD). Objectives: Memory Improvement with DHA Study (MIDAS) was a randomized, double-blind, placebo-controlled, multi-center, six month study to determine the effects of 900 mg/d DHA on improving cognitive functions (assessed by CANTAB^® cognitive battery) in healthy elderly with ARCD. Safety and tolerability were also assessed. Methods: Four hundred eighty-five subjects with a Logical Memory (WMS III) baseline score ≥1 SD below the younger adult mean were enrolled across 19 US sites. Additional study details were presented at ICAD'07. Primary outcome was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial episodic memory test. Results: Demographics: 59% female, mean age 70 ± 9, mean education 14.6 ± 2.6 years. Primary efficacy showed significantly fewer errors made on the PAL with DHA versus placebo at six months compared to baseline (diff. score -1.63 ± 0.76, p < 0.03). A significant decrease in heart rate (DHA change from baseline of -3.2 vs. -1BPM, p < 0.03) occurred and highly correlated with week 24 plasma levels (p < 0.01). Blood pressure and body weight remained unchanged between groups. Abeta_1-40,1-42 and hs-CRP plasma levels were not significantly different. Plasma phospholipid DHA levels doubled (3.2 to 6.4 weight%, p < 0.001) and correlated with the PAL response (p < 0.04). Compliance was >82%, no treatment-related SAEs were reported and the number of subjects with SAEs were equivalent across the 2 arms. Conclusions: Six month supplementation with DHA (900 mg/d) improves memory function and decreases heart rate in healthy older adults with ARCD. This improvement on the PAL is associated with a shift in the normative distribution to a younger age. DHA exhibits an excellent safety profile in this older population.