Aging metrics incorporating cognitive and physical function capture mortality risk: results from three prospective cohort studies

Abstract Background: The aims of this study were to: 1) describe the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function; 2) examine the associations of the three metrics with mortality; and 3) develop and validate a new simple functional score for mortality prediction. Methods: The three aging metrics were the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them with data from two large cohort studies: the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazard regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. A new functional score was developed and validated in the Rugao Ageing Study (RAS), an independent dataset. Results: In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2%, 16.6%, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR)=2.87, 95% confidence interval (CI)=1.74, 4.74; FI, OR=1.94, 95% CI=1.50, 2.50; MCR, OR=1.27, 95% CI=1.00, 1.62). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement, and continuous net reclassification improvement (all P <0.001). These results were replicated in NHANES. Furthermore, we developed a new functional score by selecting six self-reported items from CI-PF and FI in CHARLS, and demonstrated that it predicted mortality risk. This functional score was further validated in RAS. To facilitate the quick screening of persons with deteriorations in cognitive and physical function, we introduced a publicly available online tool designed for this new functional score. Conclusions: Despite the inherent differences in the aging metrics incorporating cognitive and physical function, they consistently capture mortality risk. The findings support the incorporation of cognitive and physical function for risk stratification in both Chinese and US persons, but call for caution when applying them in specific study settings.