Designing future nutrition clinical trials for dementia prevention

Abstract Background Past clinical trials for dementia prevention through nutrition enhancement have been wanting; and taken together have been uninformative, and generally yielded uncertain outcomes. Method A study group of researchers reviewed past experiences and examples of prevention trials involving nutritional interventions, including design, execution, specific treatments, practical problems in execution, and suggested improvements. Result Past trials show substantial variations in design, types of interventions, timing of treatments, outcomes, duration, and differing views of life course or at‐risk models. We identified, first, an overall lack of effectiveness demonstrated in these prevention trials; and, second, numerous methodologic limitations, including high risks for bias, limited external validity or generalizability that considerably limit the inferences that can be made about outcomes. Further, we identified considerable practical challenges in designing and successfully implementing these long‐term trials. Specific issues involve identifying, defining, and recruiting appropriate research subjects, the nature and conceptualization of the interventions, e.g., single molecule or multidomain, compliance and length of these long‐term trials, and appropriate intermediate and final outcomes that track efficacy. The effectiveness of a given nutritional intervention may depend as well on when in the life course it is implemented. Conclusion Informed by previous trials, we conclude with recommendations for a range of approaches to designing nutritional trials for the prevention of dementia that address nutritional interventions, minimize risk of bias, and that are more likely to be seen as ecologically valid.