BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are the common causes of dementia. Mild cognitive impairment (MCI) refers to the clinical condition between normal aging and dementia. Recent studies have appraised the possibility that homocysteine might play a role in the pathogeneses not only of VaD but also of AD. The purpose of this study was to investigate the relations of AD, VaD and MCI with homocysteine. METHODS: The study population consisted of 712 consecutive subjects, 629 of whom were eligible for analyses. The plasma total homocysteine was measured in 409 non-demented elderly control subjects, 102 MCI, and 118 demented patients with a clin-ical diagnosis of AD (n=68) or VaD (n=50). RESULTS: Homocysteine was significantly increased in patients with AD (13.9+/-4.1 ?mol/L; p<0.001), VaD (13.6+/-5.8 ?mol/L; p<0.01), and MCI (13.3+/-5.6 ?mol/L; p<0.001) as compared to controls (11.3+/-4.6 ?mol/L). Subjects in the highest homocysteine tertile had significantly higher adjusted odds ratio (AORs) for AD (AOR, 7.42; 95%CI, 3.01-18.30), VaD (AOR, 3.50; 95%CI, 1.51-8.11), and MCI (AOR, 2.40; 95%CI, 1.24-4.63). Only in the subjects with AD, the AOR was significantly higher in the middle homocysteine tertile than in the lowest tertile (AOR, 2.60; 95%CI, 1.11-6.11). In addition, homocysteine was correlated with folate, vitamin B12, age, depression, and MMSE scores, but not with schooling years. CONCLUSIONS: In this study, significantly elevated homocysteine levels were found in patients with AD, VaD, and MCI. These findings suggest that hyperhomocysteinemia might be a risk factor for cognitive decline in the elderly.