There is conflicting evidence that antioxidants contribute to maintaining cognitive function in elderly subjects. We investigated whether vitamin E plasma levels are related to the presence of dementia and cognitive impairment in a population-based cohort study conducted in Italy. A total of 1033 participants aged at least 65 years received clinical and neuropsychological examinations, donated blood for vitamin E analysis and had their diets assessed. Participants with plasma vitamin E levels in the bottom tertile had a significantly higher probability of being demented (OR 2.6, 95% CI 1.0–7.1) and also of suffering from cognitive impairment (OR 2.2, 95% CI 1.2–4.2) compared to those in the highest vitamin E tertile after adjustment for age, gender, education, lipid levels, energy intake, vitamin E intake, and smoking. This study supports the notion that higher vitamin E plasma levels might provide significant protection against cognitive impairment and dementia in elderly subjects.