Background: Both cognitive function and gait speed are important correlates of disability. However, little is known about the combined effect of cognitive function and gait speed on multiple domains of disability as well as about the role of gait speed in the association between cognitive function and late-life disability. Objective: To investigate (1) how cognition and habitual gait speed are related to late-life disability; (2) the role of habitual gait speed in the cognitiondisability association; and (3) the combined effect of cognitive function and habitual gait speed on late-life disability. Method: Participants (>60 years, n = 2,481) were from the National Health and Nutrition Examination Survey 1999–2002. Disability in activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), and lower extremity mobility (LEM) was obtained by self-report. Cognitive function was measured by a 2-min timed Digit Symbol Substitution Test (DSST), an executive function measure from the Wechsler Adult Intelligence Test. Habitual gait speed was obtained from a 20-foot timed walk. Multiple logistic regression was used to assess the association between cognitive function and disability. Results: Cognitive function was associated with decreased likelihood for disability in each domain. The odds ratios (ORs) for disability in ADL, IADL, LSA, and LEM for each standard deviation (SD) increase in the DSST score were 0.47 (95% confidence interval [CI] = 0.34–0.64), 0.53 (95% CI = 0.42–0.67), 0.61 (95% CI = 0.47–0.79), and 0.73 (95% CI = 0.61–0.86), respectively, in the multi-variable models. After additional adjustment for habitual gait speed in the cognition-disability relationship, DSST score was no longer a significant correlate for LSA and LEM disability. The strength of the association between DSST score and disability in ADL/IADL was also diminished. The attenuated association between cognition and disability implies that limitation in gait speed likely mediates the association between cognitive function and disability. We found additive effects of cognition and habitual gait speed on late-life disability. The OR of disability in respective domains were lowest among participants with high-DSST score (high executive function) and with high gait speed. In contrast, the OR tended to be highest among participants with low-DSST score (low executive function) and low gait speed. Conclusion: Cognitive function was associated with multiple domains of disability. There was a joint effect of cognitive function and gait speed on late-life disability. This study also suggested that habitual gait speed partially mediated the inverse association between cognitive function and late-life disability, providing a mechanistic explanation in the context of disablement process.

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