Objectives.We aimed to examine associations between each of three leisure activities (Cognitive, Physical, and Social) and performance in selected cognitive domains (Speed, Memory, Verbal ability, and Executive functions) and global cognition. We also aimed to explore associations between medical and health factors and late-life cognition.Method.Our sample comprised 119 pairs of monozygotic twins from the Older Australian Twins Study. Their mean age was 71 years and 66% were women. We used a discordant co-twin design, with cognitive performance measures as dependent variables and leisure activities as independent variables. Multiple regression analyses were performed, adjusting for potentially relevant medical and health factors. RESULTS: Discordance in Cognitive Activity and Social Activity participation was positively associated with discordance in performance on some cognitive domains. There were no associations between Physical Activity participation and cognition. Discordance in several cardiovascular, frailty, and sensory variables was associated with discordance in cognitive performance measures.Discussion.This study identified lifestyle and health-related influences on late-life cognition. Our findings not only help in understanding the neurobiological mechanisms, they also have practical implications for interventions to prevent or slow age-related cognitive decline.