This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer's disease (AD).A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain.An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the β-amyloid1-42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice.Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD.