The possible impact of diet, particularly the intake of fatty acids, on cognitive decline and dementia was addressed recently by several studies. We investigated the role of dietary fatty acids on the rate of mild cognitive impairment (MCI) in a population-based, prospective study carried out on 278 and 186 nondemented elderly subjects (65-84 years) at the 1st (1992-1993) and 2nd (1995-1996) survey from the cohort of Casamassima, Bari, Italy (n=704), one of the eight centers of the Italian Longitudinal Study on Aging. During the median follow-up of 2.6 years, 18 new events of MCI were diagnosed, and high polyunsaturated fatty acids (PUFA) intake appeared to be a protective factor against the development of MCI [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.43-0.98, trend-test, df=1, p<0.04]. However, when we controlled for the possible confounders (age, sex, education, Charlson comorbidity index, and total energy intake), the HR slightly changed, and the highly skewed 95% CI, while not statistically significant, may be important (HR: 0.62, 95% CI: 0.34-1.13, p=0.12). In our population, dietary fatty acids intakes were not associated with incident MCI in older age, only high PUFA intake evidenced a borderline nonsignificant trend for a protective effect against the development of MCI.