An increasing body of epidemiological evidence suggested that elevated saturated fatty acids could have negative effects on age-related cognitive decline (ARCD) and mild cognitive impairment (MCI). Furthermore, a clear reduction of risk for cognitive decline has been found in population samples with elevated fish consumption, high intake of monounsaturated fatty acids, and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. In the present article, on the basis of increasing body of evidence from cross-sectional and longitudinal population-based studies, we discussed the issue of the possible impact of dietary PUFA (both n-6 and n-3) on ARCD, MCI, and Alzheimer's disease.