Population aging is a global phenomenon and will have a major impact on Latin American and Caribbean countries in the coming decades. It is therefore necessary to develop preventive measures and to conduct scientific studies into treatments for diseases, particularly the neurodegenerative ones, which affect neuroplasticity. Serious games are video games that have educational purposes in addition to entertainment. These games seem to be associated with preventive activity against cognitive decline in the elderly, but there is still a lack of solid studies to prove their validity. The aim of this study was to evaluate brain changes in elderly people resulting from the use of serious games, in order to investigate possible alterations in the neuroplasticity of these participants, and compare these changes with cognitive and psychological changes associated with the use of the games. Seventeen participants played serious games for 3 to 5 months and were evaluated pre- and post-intervention using functional magnetic resonance imaging, to map functional connectivity, and with cognitive and psychological tests. We found a decrease in functional connectivity between the orbitofrontal cortex (OFC) and the supplementary motor region and also between the OFC and the motor cortex region of the left hand. We also found an increase in information retention (Rey Auditory-Verbal Learning Test) and in memory (animal fluency test). This indicates that participants improved their memory after the intervention, and also had significant alterations in neural networks related to motor control, sensory integration, emotional processing, and reward mechanisms. More studies with a larger sample are needed to refine these conclusions.