See corresponding editorial on page 329. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging1–3

Background: High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline. Objective: We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60–101 y. Design: Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical exami-nations and expert adjudication. We used proportional hazards mod-els to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association. Results: High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95 % CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P 0.04) and lower (HR: 0.94, P 0.015) than the risk for those in the middle tertile. Conclusions: Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND. Am J Cli