The incidence of aging-related cognitive decline is increasing with population aging. It is urgent to explore ways to ameliorate aging-related cognitive decline. Cognitive-exercise dual-task intervention has shown beneficial effects on improving cognition in aging cohorts, but the mechanisms of the effects remain unclear. In this study, 18-month-old Sprague Dawley rats served as a model of natural aging. First, the performance in the Morris water maze test and the change in synaptophysin content in the hippocampus were used to investigate the cognitive decline of 18-month-old rats. Then, a batch of 18-month-old rats was treated with cognitive, exercise, or cognitive-exercise dual-task intervention for 12 weeks. The novel object recognition test was used to assess cognitive ability. Enzyme-linked immunosorbent assay and Western blotting were used to detect the levels of oxidative stress molecules and synaptic plasticity-related proteins. We found that cognitive-exercise dual-task intervention improved the discrimination index of natural aging rats. After dual-task intervention, the expression levels of synaptophysin, brain-derived neurotrophic factor, superoxide dismutase, and glutathione peroxidase were increased, and the expression level of lipid peroxide malondialdehyde was decreased. Furthermore, the effect of dual-task intervention on synaptic plasticity-related proteins and oxidative stress indicators was greater than that of single cognitive or exercise intervention. In conclusion, cognitive-exercise dual-task intervention can significantly ameliorate aging-related cognitive decline, and the improvement might be related to the reduction of oxidative stress and the enhancement of synaptic plasticity. The effect of cognitive-exercise dual-task intervention may be better than that of single cognitive or exercise intervention.
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