This review summarizes empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD), drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors, and nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention. First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces risk of AD. Second, the absence of vascular risk factors such as diabetes mellitus, hypertension, hypercholesterol, and obesity reduces risk of AD. More prevention trials are warranted to investigate the preventive effects of an active and stimulating lifestyle on the one hand, and vascular health, on the other, in delaying the onset of AD or slowing its progression.