Prevention of sporadic Alzheimer's disease: lessons learned from clinical trials and future directions

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.