1. Introduction
Dementia, memory complaints, cognitive decline
Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline.Dementia is a serious social problem globally, and thus, preventing cognitive decline is important. A well-balanced diet is crucial for maintaining cognitive function [ARA and DHA are abundant in the brain and are major components of phospholipids. The amount of these fatty acids in the brain decreases with aging [Among more than 1000 carotenoids found in nature [In addition, the effects of DHA and EPA supplementation on memory function have had no effect in previous studies on healthy older individuals without cognitive decline [Based on the facts that ARA, DHA, EPA, L, and Z (LCPUFAs + LZ) are present in the brain and several reports suggest memory function improvement with some components, a combination of these components may improve memory function in healthy older individuals. However, no previous studies have confirmed their effects. Therefore, in the present study, the following two hypotheses were formulated. Hypothesis 1: Food supplements containing LCPUFAs + LZ improve memory function in healthy older individuals with memory complaints. Hypothesis 2: Memory function is more likely to improve by LCPUFAs + LZ in participants with cognitive decline than in participants with normal cognitive function. For the exploratory examination of Hypothesis 1, an exploratory trial (Trial 1) was conducted in healthy older individuals with memory complaints. A confirmatory trial (Trial 2) was conducted after Trial 1 was deemed to be meaningful. To examine Hypothesis 2, a subgroup analysis of participants with cognitive decline in Trials 1 and 2 was performed. Combined analyses for subgroups of participants with cognitive decline in Trials 1 and 2 were also performed to comprehensively interpret the results of the two individual subgroup analyses with a larger sample size than that of the individual trials.