Summary Interventions that have even quite modest effects at the individual level could drastically reduce the future burden of dementia associated with Alzheimer's disease at the population level. ...In the past three decades, both pharmacological and lifestyle interventions have been studied for the prevention of cognitive decline or dementia in randomised controlled trials of individuals mostly aged older than 50–55 years with or without risk factors for Alzheimer's disease. Several trials testing the effects of physical activity, cognitive training, or antihypertensive interventions showed some evidence of efficacy on a primary cognitive endpoint. However, most of these trials had short follow-up periods, and further evidence is needed to confirm effectiveness and establish the optimum design or dose of interventions and ideal target populations. Important innovations in ongoing trials include the development of multidomain interventions, and the use of biomarker or genetic inclusion criteria. Challenges include the use of adaptive trial designs, the development of standardised, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings.
Alzheimer's dementia affects more than 40 million people worldwide with substantial increases in prevalence anticipated. Interventions that either modify risk or reduce the development of early ...disease could delay the onset of dementia or reduce the rate of cognitive and functional decline. The European Prevention of Alzheimer's Dementia (EPAD) is a public-private consortium, funded by the Innovative Medicines Initiative, designed to increase the likelihood of successful development of new treatments for the secondary prevention of Alzheimer's dementia. EPAD will help with testing of different agents in this pre-dementia population through four components: improvement of access to existing cohorts and registries, development of the EPAD Registry of approximately 24,000 people who might be at increased risk of developing Alzheimer's dementia, establishment of the EPAD Longitudinal Cohort Study of 6000 people at any one time, and establishment of an adaptive, proof-of-concept trial including 1500 participants at any given time. The need for EPAD and its key design elements are described, and we discuss EPAD in relation to similar projects in progress. These parallel efforts reflect the need for a coordinated, worldwide battle against dementia, in which EPAD will play a crucial role.