668 Am J Clin Nutr 2003;77:668–73. Printed in USA. © 2003 American Society for Clinical Nutrition Homocysteine and cognitive function in healthy elderly community dwellers in Italy1–3

Background: Elevated plasma total homocysteine (tHcy) con-centrations are common in the elderly and have been suggested to be a risk factor for dementia. Objective: In an elderly population, we examined the relation between plasma tHcy and scores on the Mini-Mental State Exam-ination (MMSE), a commonly used screening measure of cogni-tive impairment in general practice. Design: Fasting plasma tHcy concentrations were measured in 650 healthy, cognitively normal Italian community dwellers aged ≥ 65 y (x – ± SD: 72.8 ± 6.0 y). Socioeconomic status; serum folate, vitamin B-12, and creatinine; other potential dietary and lifestyle determinants of tHcy; and conventional vascular disease risk factors were also assessed. Results: Subjects with MMSE scores of 26–28 had higher plasma tHcy concentrations (12.7 mol/L; range: 12.2–13.2 mol/L) than did those with scores> 28 (11.9 mol/L; 11.4–12.3 mol/L; P < 0.01). Subjects with scores of 24–25 had higher plasma tHcy concentrations (14.5 mol/L; 13.5–15.6 mol/L) than did sub-jects with scores of 26–28 (P < 0.01) or> 28 (P < 0.001). The risk of hyperhomocysteinemia (plasma tHcy> 15 mol/L) was higher in subjects with scores of 24–25 (odds ratio: 3.81; 95 % CI: 1.9, 7.5) or 26–28 (odds ratio: 1.96; 95 % CI: 1.3, 3.0) than in those with scores> 28. The results did not change after adjustment for conventional vascular risk factors and for age, medical, dietary, and lifestyle determinants of plasma tHcy. Conclusion: Elevated plasma tHcy has an independent, graded association with concurrent cognitive impairment as measured with the MMSE in healthy elderly community dwellers. Am