Abstract
Alzheimer disease (AD) poses a major threat to medicine and society, but recent epidemiologic data indicate declining incidence of the disease. This development may be due to prevention of many cases by attention to modifiable risk factors. Meanwhile, all treatment efforts using drugs targeting amyloid have failed. In contrast to the assumption of recent decades that sporadic AD is primarily a genetic disease in which neuritic plaques and neurofibrillary tangles are mainly responsible for clinical features, it is now time for a more nuanced approach that considers the role of environmental factors preceding dementia onset and the appearance of aggregated proteins. This view of AD has important implications for medical care and health policy, and for counseling individuals to adopt lifestyle strategies that can be effective for prevention.