The objective was to study the associations between participation in different types of mentally stimulating leisure activities and status as Alzheimer's disease (AD) case or normal control. Research suggests that participation in leisure activities, especially mentally stimulating activities, is associated with a lower risk for AD. However, no study has yet evaluated associations between AD and different types of mental leisure activities, especially those involving "novelty seeking." The authors used a case-control design to compare participation in activities across the life span in persons with AD and normal controls. Cases (n = 264) were recruited from clinical settings and from the community. Controls were drawn from 2 populations. Control group A members (n = 364) were the friends or neighbors of the cases or members of the same organizations to which the cases belonged. Control group B members (n = 181) were randomly drawn from the community. The 2 control groups did not differ in their responses to most activity questions, so they were combined. Factor analysis of activity questions identified 3 activity factors: (1) novelty seeking; (2) exchange of ideas; and (3) social. Logistic regression analysis indicated that, adjusting for control variables, greater participation in novelty-seeking and exchange-of-ideas activities was significantly associated with decreased odds of AD. The odds of AD were lower among those who more often participated in activities involving exchange of ideas and were lower yet for those who more frequently participated in novelty-seeking activities. We conclude that participation in a variety of mental activities across the life span may lower one's chances of developing AD.