Homocysteine has been associated with an increased risk of cardiovascular disease. Cardiovascular diseases have been related to cognitive decline. The authors investigated the association of homocysteine with concurrent cognitive impairment and subsequent cognitive decline in a random sample of 702 community-dwelling respondents aged 55 years or over to the prospective Rotterdam Study in 1990-1994. Multiple logistic regression was used to calculate odds ratios and 95 percent confidence intervals for the association between total homocysteine levels and cognitive impairment (Mini-Mental State Examination (MMSE) score <26) and cognitive decline (drop in MMSE score of >1 point/year). Mean duration of follow-up was 2.7 years. After adjustment for age, sex, and education, there was no relation between total homocysteine and cognitive impairment (highest vs. lowest tertile: odds ratio (OR) = 1.30, 95% confidence interval (CI): 0.50, 3.38) or cognitive decline (middle vs. lowest tertile: OR = 1.14, 95% CI: 0.67, 1.93; highest vs. lowest tertile: OR = 0.91, 95% CI: 0.52, 1.58). Subjects who were lost to follow-up due to death or nonresponse had slightly higher age-adjusted homocysteine levels and lower MMSE scores at baseline. Sensitivity analyses showed that selective loss to follow-up was not a likely explanation for the absence of an association in the participants. Although a relation between homocysteine and reduced cognitive function is biologically plausible, this study suggests no such association in a community-based sample of the elderly.