4. Discussion
age-related cognitive decline, memory complaints, dementia, cognitive decline
ADVERSE EVENTS
In the present study, we conducted a combined analysis of two trials to evaluate the effects of LCPUFAs + LZ supplementation on memory function in healthy older Japanese individuals with memory complaints without dementia. There were no significant differences between groups in the combined PPS analysis. However, significant improvements were observed in the combined analysis of the subgroup with cognitive decline. This study suggests for the first time that the combined intake of LCPUFAs and LZ could potentially improve memory function in healthy older Japanese individuals with cognitive decline without dementia.In both trials, the cognitive function of the participants was considered to be at the same level as that of the general older population, as the average MoCA-J scores obtained at baseline (In the PPS analysis in Trial 2 of our study, which was a confirmatory study, no significant changes were noted in episodic memory scores. In Trial 2, in which the number of cases was designed based on the positive changes observed in Trial 1, no significant efficacy of LCPUFAs + LZ was detected. One factor for which no significant difference was detected was the difference between the two trials in the distribution of the baseline cognitive function scores. In Trial 1, the median MoCA-J score was 23, and the percentage of those with a score below 23 was 44%. In contrast, the median score in Trial 2 was 24, and the percentage of participants with a score below 23 was 33%, indicating that the participants in Trial 2 had higher cognitive function. In previous reports, food components were found to have a greater impact on the memory function of participants with lower cognitive function [In the present study, the combined analysis of the subgroup with cognitive decline, LCPUFAs + LZ supplementation resulted in a significant improvement of composite memory. For the composite memory scores in Cognitrax, the average score for subjects 60–69 years old was 94.6, and 90.7 for those 70–79 years old, reflecting a decrease of 3.9 points over the decade [The improvement in visual memory was less than verbal memory for both trials. In addition, several other intervention studies using Cognitrax [Furthermore, when setting the threshold for MoCA-J scores in the subgroup analysis at 22 and 21 points (rather than 23), significant improvements were consistently observed in the combined analysis. Additionally, no significant differences were detected for composite memory in the combined PPS analysis or subgroups with MoCA-J scores ≥23. These results suggest that LCPUFAs + LZ intake helps improve memory function in healthy older individuals with cognitive decline, thereby supporting Hypothesis 2: Memory function is more likely to improve by LCPUFAs + LZ in participants with cognitive decline than in participants with normal cognitive function. These subgroup analyses based on baseline cognitive status are important for clarifying who may benefit from the intervention, which can pave the way for more efficient treatment strategies.In this study, the PPS analysis found that there was no efficacy on memory function, which is consistent with previous studies. For example, Dangour et al. found that DHA (500 mg/day) and EPA (200 mg/day) for 24 months had no effect on memory function in cognitively normal older people [Improvements in some memory function test items were seen in a study in which DHA 800 mg/day and L 12 mg/day were consumed for four months [The present study found efficacy on memory function in healthy older Japanese individuals with cognitive decline without dementia, which is consistent with previous research. For example, Yurko-Mauro et al. reported that 24 weeks of DHA (900 mg/day) improved memory function in healthy subjects with age-related cognitive decline [According to previous reports, LCPUFA [Synaptic plasticity, which is necessary for memory function and declines with age, can be improved by the intake of ARA, DHA, or EPA [This study has several strengths. No adverse events associated with the supplementation of LCPUFAs + LZ were observed, indicating that LCPUFAs + LZ supplementation in both Trials 1 and 2 can be considered safe. In addition, the average intake rates of the capsules in both trials used for the combined analysis were high, at more than 99% each. In Trial 1, significant increases in ARA (+ 0.7% at week 12 and +0.7% at week 24), DHA (+ 1.0% at week 12 and +0.8% at week 24), and EPA (+ 0.4% at week 12 and +0.3% at week 24) compositions in plasma PL, and L (+ 0.20 μg/mL at week 12 and +0.19 μg/mL at week 24), and Z (+ 0.06 μg/mL at week 12 and +0.05 μg/mL at week 24) concentrations in serum were observed in the LCPUFAs + LZ group in Trial 1 (This study also has three major limitations. First, the data from the combined analysis in which the effect of LCPUFAs + LZ was detected were based on data from a subgroup analysis. Second, the scoring test used in this study, Cognitrax, provides a relatively easy task, and the results may change if the difficulty of the test changes. It is necessary to examine how the use of a relatively difficult test, for example, the Wechsler memory scale of logical memory, would affect the results for subjects other than those with cognitive decline. Third, this study was conducted on Japanese participants, and it is unknown whether similar results would have been obtained if the study had been conducted on people in low-income countries with different educational environment and nutritional status than Japan. However, ARA, DHA, and EPA which are essential fatty acids, and LZ which exist in the human brain, have antioxidant and anti-inflammatory effects, are considered necessary for the human body and brain, regardless of the environment. In order to clarify the efficacy of these components in non-Japanese individuals, it is necessary to conduct studies in other countries.