The challenge of dementia prevention trials and the role of quasi-experimental studies.

Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. HIGHLIGHTS: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia.