To test whether elevated homocysteine levels are associated with an increased risk of decline in physical function in older persons.

We performed a prospective cohort study of 499 highly functioning men and women aged 70 to 79 years who were enrolled in the MacArthur Studies of Successful Aging. We measured total homocysteine levels and performance-based physical function at baseline; physical function measures were repeated an average of 28 months later. A summary measure of physical performance from tests of balance, gait, lower body strength and coordination, and manual dexterity was developed, and a change score was calculated as the difference in scores from 1988 to 1991.

The mean (±SD) homocysteine level was 11.6 ± 4.3 μmol/L. With each SD increase in homocysteine, there was an increased risk of being in the worst quartile of decline in physical function (odds ratio = 1.5; 95% confidence interval: 1.2 to 1.9) in analyses that adjusted for age, sex, baseline physical performance, smoking status, vitamin B₁₂ levels, and incident stroke. Similar results were seen when change in physical performance was treated as a continuous variable.

Older persons with elevated plasma homocysteine levels are at an increased risk of decline in physical function.