Nitric oxide is involved in normal physiological functions and also in pathological processes leading to tissue damage due, in part, to its free radical nature (oxidative stress). Oxidative stress and vascular dysfunction have been recognized as contributing factors in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VD). In order to study the possible links between these processes and dementia, we have analysed plasma amyloid-beta(1-42) levels (Abeta) and total nitric oxide (NOx), apolipoprotein E (ApoE), lipids, vitamin B12, and folate concentrations in the serum of 99 patients with dementia and 55 age-matched non-demented controls. Both nitrate and nitrite levels were measured by a colorimetric method using Griess Reagent and plasma Abeta levels were analysed by a hypersensitive ELISA method. Our data showed a significant decrease of serum NOx levels in dementia, especially in probable AD and VD patients, as compared with controls. We observed a weak correlation between serum NOx levels and cognitive deterioration in dementia; however, NOx levels were not associated with ApoE and Abeta levels. In dementia and controls, a similar correlation pattern between HDL-cholesterol versus NOx was found. No apparent association between NOx, Abeta and AD-related genes [APOE (apolipoprotein E), PSEN1 (Presenilin 1)] was observed. Our data suggest that NOx may contribute to the pathogenesis of dementia through a process mediated by HDL-cholesterol.