Nutrition affects the brain throughout life, with profound implications for cognitive decline and dementia. These effects are mediated by changes in expression of multiple genes, and responses to nutrition are in turn affected by individual genetic variability. An important layer of regulation is provided by the epigenome: nutrition is one of the many epigenetic regulators that modify gene expression without changes in DNA sequence. Epigenetic mechanisms are central to brain development, structure and function, and include DNA methylation, histone modifications and non-protein-coding RNAs. They enable cell-specific and age-related gene expression. Although epigenetic events can be highly stable, they can also be reversible, highlighting a critical role for nutrition in prevention and treatment of disease. Moreover, they suggest key mechanisms by which nutrition is involved in the pathogenesis of age-related cognitive decline: many nutrients, foods and diets have both immediate and long-term effects on the epigenome, including energy status, that is, energy intake, physical activity, energy metabolism and related changes in body composition, and micronutrients involved in DNA methylation, for example, folate, vitamins B6 and B12, choline, methionine. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Future studies linking nutrition with advances in neuroscience, genomics and epigenomics should provide novel approaches to the prevention of cognitive decline, and treatment of dementia and Alzheimer's disease.