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The results of the study, published in 2017, failed to demonstrate a significant slowing of cognitive decline during the 3-year study period, although subgroup analyses suggested possible (and modest) benefits for individuals with elevated brain amyloid accumulation and those who were carriers of the APOE4 allele (Andrieu et al., Designing Future Interventions Given the complex interaction of APOE4 with several genetic and environmental factors that shape the response to diet, we propose considering novel designs for nutritional clinical trials aiming to improve cognitive outcomes in APOE4 carriers