Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults

OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone. DESIGN: Observational cohort study. SETTING: Community. PARTICIPANTS: Three thousand one hundred fifty-six (43% men, 29% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher. MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years. RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively). CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.