The purpose of this commentary is briefly to review the genetic, social, demographic, and environmental factors associated with Alzheimer disease with the specific purpose of planning an intervention to prevent or possibly delay the onset of disease. Complex disorders such as Alzheimer disease are the result of one or more genes and other contributing risk factors. For example, apolipoprotein E (APOE) genotypes can indicate a degree of susceptibility, but the gene is neither "necessary nor sufficient" to cause the disease. Thus, many potential risk factors remain to be identified. The association between Alzheimer disease and APOE also varies with age, genetic background, and ethnic group. While the use of APOE genotyping has provided a method to identify individuals at greatest risk of Alzheimer disease, how other factors modify the degrees of the APOE-related risk needs to be further investigated. Moreover, the effect of APOE on disease course and various noncognitive manifestations warrant scrutiny. Because risk prediction is not straightforward, practical issues related to developing a national strategy to prevent or delay the onset of Alzheimer disease require careful consideration, planning, and an organized interdisciplinary effort.