Paraoxonase 1 (PON1), an A-esterase with peroxidase-like activity present on the surface of HDL, decreases the peroxidation of LDL. Serum PON1 activity (PON1a) decreases with aging and in disorders associated with a high risk of adverse cardiovascular events (acute myocardial infarction, diabetes mellitus, and chronic renal failure). The implication of vascular factors in Alzheimer-type dementia (ATD) is strongly suspected. We measured PON1a by spectrophotometry using the paraoxon substrate in 180 healthy subjects (controls; mean age: 75.3 +/- 8.9 years; 98 women) and 154 patients admitted for cognitive testing. According to criteria, 45 patients had mild cognitive impairments (MCI; mean age: 75.6 +/- 9.3 years; 28 women), 60 had ATD (mean age: 75.6 +/- 8.3 years; 47 women), and 49 had vascular dementia (VaD; mean age: 77.5 +/- 7.2 years; 33 women). Mean PON1a was lower in VaD (0.25 +/- 0.1 U/mL) than in controls or ATD (both 0.41 +/- 0.2 U/mL, p < 0.01). Mean PON1a values in MCI (0.34 +/- 0.2 U/mL) and ATD (0.41 +/- 0.2 U/mL) were not significantly different. In multiple linear regression, PON1a was negatively correlated with male sex, age, and VaD, and positively correlated with ATD (each correlation p < 0.001). As shown in other high-risk cardiovascular disorders, PON1a seems to be a reliable marker of VaD. Its modification in Alzheimer's disease supports the implication of vascular risk factors in this type of dementia.