Recent epidemiological evidence showed that dietary fatty acids, antioxidants, and micronutrients appear to have a role in cognitive decline, and may permit a beneficial effect on the risk of dementia and predementia syndromes. We discussed in the present paper the issue of the suggested protective role of polyunsaturated fatty acids (PUFA) on Alzheimer's disease, mild cognitive impairment, and other predementia syndromes, supported by the findings of the Italian Longitudinal Study on Aging (ILSA) and other population-based studies. In particular, we discussed the possible metabolic link of plasma S-adenosylhomocysteine concentrations with PUFA erythrocyte composition in explaining this suggested protective role of fatty acids against dementia and predementia syndromes.