Relationship of homocysteine levels to quadriceps strength, gait speed, and late-life disability in older adults

Background. Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with multiple age-related problems including cardiovascular diseases, dementia, and osteoporotic fracture. Disability is one of the most common features in older adults. However, little is known about the role of homocysteine in physical disability among older adults. Methods. Participants (>60 years, N = 1677) were from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Nineteen questionnaires in five major domains were administered to assess the level of difficulty in performing various tasks: activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA). Peak quadriceps strength was obtained by using an isokinetic dynamometer. Habitual gait speed was obtained from a 20-foot timed walk. Homocysteine levels were measured by the Abbott homocysteine assay, an automated fluorescence polarization immunoassay (FPIA). Results. Elevated homocysteine was associated with disability in ADL, IADL, LSA, and GPA after multivariate adjustment. The odds ratios (ORs) for disability in these domains comparing participants in the highest quartile of homocysteine to those in the lowest were 2.18 (95% confidence interval [CI], 1.32-3.59) for ADL; 1.62 (95% CI, 1.02-2.57) for IADL; 2.00 (95% CI, 1.14-3.51) for LSA; and 1.52 (95% CI, 1.05-2.21) for GPA. The strength of associations weakened somewhat after additional adjustment of quadriceps strength and/or gait speed, suggesting a mediating role of quadriceps strength and gait speed in the association between homocysteine and disability. Homocysteine had an inverse relationship to quadriceps strength and gait speed. Likewise, quadriceps strength seemed to mediate the inverse association between homocysteine and gait speed. Conclusions. Elevated homocysteine is associated with multiple domains of disability mediated in part by muscle strength and gait speed. The results suggest that homocysteine levels may be important indicators of performance status in older adults.