Objectives: Mentally stimulating leisure activities and cognitive interventions are associated with delayed cognitive decline, although evidence has not been unequivocal, possibly due to differential contribution of the two types of activities. This study aimed to examine the respective contributions of mentally active lifestyle and structured cognitive programs on cognitive changes in older adults. Methods: This was a 2-year prospective cohort study of 1,793 healthy older adults. We recorded mentally active lifestyle and participation in cognitive program. Cognitive function was assessed using the Montreal Cognitive Assessment. Physical frailty was also screened for the potential effect on cognition. Results: Compared to the mentally inactive group, the mentally active group had better baseline cognitive functioning (standardized mean difference of 0.08, t = −3.8; p < 0.001), but both groups showed a mild cognitive decline over time (both p < 0.05). The mentally active group were less physical frail, more physical independent, and less depressed. Participation in structured cognitive programs was associated with cognition improvement, in older persons who had a mentally active or inactive lifestyle (standardized mean differences of 0.22 and 0.27, respectively; both p < 0.01), but these gains significantly diminished at year 2 in the latter group. Lower baseline cognitive function and higher level of physical frailty predicted greater cognitive gains from structured cognitive programs. Conclusion: Both a mentally active lifestyle and structured cognitive programs contributed to better cognition. Structured cognitive programs appeared to add on to the benefits of a mentally active lifestyle, and predicted cognitive changes regardless of lifestyle.