Dementia, a major cause of disability and institutionalization in older people, poses a serious threat to public health and to the social and economic development of modern society. Alzheimer's disease (AD) and cerebrovascular diseases are the main causes of dementia; most dementia cases are attributable to both vascular and neurodegenerative brain damage. No curative treatment is available, but epidemiological research provides a substantial amount of evidence of modifiable risk and protective factors that can be addressed to prevent or delay onset of AD and dementia. Risk of late-life dementia is determined by exposures to multiple factors experienced over the life course, and the effect of specific risk/protective factors depends largely on age. Moreover, cumulative and combined exposure to different risk/protective factors can modify their effect on dementia/AD risk. Multidisciplinary research involving epidemiology, neuropathology, and neuroimaging has provided sufficient evidence that vascular risk factors significantly contribute to the expression and progression of cognitive decline (including dementia) but that active engagement in social, physical, and mentally stimulating activities may delay the onset of dementia. However, these findings need to be confirmed by randomized controlled trials (RCTs). A promising strategy for preventing dementia is to implement intervention programs that take into account both the life-course model and the multifactorial nature of this syndrome. In Europe, there are three ongoing multidomain interventional RCTs that focus on the optimal management of vascular risk factors and vascular diseases. The RCTs include medical and lifestyle interventions and promote social, mental, and physical activities aimed at increasing the cognitive reserve. These studies will provide new insights into prevention of cognitive impairment and dementia. Such knowledge can help researchers plan larger, international prevention trials that could provide robust evidence on dementia/AD prevention. Taking a step in this direction, researchers involved in these European RCTs recently started the European Dementia Prevention Initiative, an international collaboration aiming to improve strategies for preventing dementia.