BACKGROUND: Conflicting results have been reported on the association of plasma total homocysteine (tHcy) and cholesterol levels in Alzheimer disease (AD). The objective of this study was to determine the relationship between cognitive performance and plasma levels of tHcy and its biological determinants folate and vitamin B(12), and lipids in clinically diagnosed AD patients. METHODS: A cross-sectional database review was performed on two separate groups of patients (n = 191). Mini-Mental State Exam (MMSE) scores, plasma levels of tHcy, vitamin B(12), folate, cholesterol, and triglycerides were analyzed. RESULTS: The MMSE scores were inversely correlated with age, plasma levels of tHcy and LDL cholesterol. However, only the inverse relationship between MMSE scores and LDL cholesterol levels persisted after adjustment for age, sex, and status of statin treatment. Plasma tHcy levels increased significantly with age and were inversely related to vitamin B(12) and folate levels, which modified the relationship between MMSE scores and plasma tHcy levels. CONCLUSIONS: The plasma tHcy levels appeared to relate more to aging than to cognition. Cognitive performance was inversely associated with plasma LDL cholesterol levels in AD patients. Our findings provide further evidence that high LDL cholesterol levels may play a role in the pathogenesis of AD.