There is a recent increase in the level of interest in the possible role of dietary fatty acids in age-related cognitive decline, and cognitive impairment of both degenerative (Alzheimer's disease, AD) or vascular origin. At present, several studies suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions. Furthermore, a clear reduction of risk of cognitive decline has been found in a population sample with a high intake of polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). These findings were confirmed by studies in which high intakes of n-6 PUFA, n-3 PUFA, MUFA, and weekly fish consumption, providing large amount of n-3 PUFA, appear to be protective against the risk of AD. In our elderly population from Southern Italy, elevated unsaturated fatty acids intake (MUFA and PUFA), high levels of antioxidant compounds, and very low SFA intake could act synergistically in improving cognitive performance. Epidemiological studies on the association between diet and cognitive decline suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia, both of degenerative or vascular origin. Appropriate dietary measures or supplementation with specific micro- and macronutrients might open new ways for the prevention and management of cognitive decline and dementia.