Homocysteine level and cognitive function in patients with arterial disease: The second manifestations of ARTerial disease study

OBJECTIVES: To assess the relationship between total plasma homocysteine (tHcy) level and cognitive function in patients with manifest arterial disease. DESIGN: Cross-sectional. SETTING: Patients with symptomatic cerebrovascular disease, cardiovascular disease, peripheral arterial disease, or abdominal aortic aneurysm included in the Second Manifestations of ARTerial disease study, a single-center, longitudinal study with an extensive screening program at baseline. PARTICIPANTS: Three hundred forty-five consecutively included patients, mean age 59. MEASUREMENTS: The patients underwent an extensive neuropsychological test. The cognitive domains assessed were memory, executive function, attention, and visuoperception and construction. Each raw score was transformed into standardized z-scores, and a sum score for global cognitive function was determined. Risk factors and vascular damage were measured in detail. RESULTS: Linear regression showed that elevated levels of tHcy were related to lower global cognitive function (beta=-0.065, 95% confidence interval (CI)=-0.116 to -0.013) and, more specifically, lower performance on memory (beta=-0.078, 95% CI=-0.155 to -0.002), attention (beta=-0.079, 95% CI=-0.163 to -0.005), and visuoperception and construction (beta=-0.125, 95% CI=-0.236 to -0.014) per standard deviation increase in tHcy (SD=6.4 mol/L), after adjustment for age, sex, educational level, extent of atherosclerosis, and location of vascular disease. Silent cerebral infarcts did not influence this relationship. CONCLUSION: A relationship was found between tHcy levels and cognitive function that was independent of extent and location of arterial disease. The results suggest that vascular mechanisms are not responsible for the relationship between tHcy and cognitive function.