Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical trials regarding the potential role of diet in the prevention of cognitive decline and dementia. We further discuss possible methodological limitations that might have hindered the ability of previous diet intervention trials to capture potential neuroprotective effects. Considering the overwhelming and continuously expanding societal, economic and health-care burden of Alzheimer disease and other dementias, future nutritional research must address past methodological challenges to accurately and reliably inform clinical practice guidelines and public health policies. Within this scope, we provide a roadmap for future diet intervention trials for dementia prevention. We discuss study designs involving both intensive personalized interventions - to evaluate pharmacokinetic and pharmacodynamic properties, establish neuroprotective thresholds, and test hypothesized biological mechanisms and effects on brain health and cognition through sensitive and precise biomarker measures - and large-scale, pragmatic public health interventions to study population-level benefits.