Identifying Risk Factors for All-Cause Mortality in Older Adults: Rest-Activity Rhythm, Frailty, and Metabolic Syndrome

<b>Objective:</b> This retospective cohort study examined the associations of frailty, metabolic syndrome (MetS), and circadian rest-activity rhythms (RAR) with all-cause mortality among U.S. older adults. <b>Methods:</b> NHANES 2011-2014 dataset was linked to the National Death Index through 2019. 1010 adults aged ≥ 60 years (females: 55.9%), were included. Frailty status and MetS were defined using a frailty phenotype and NCEP ATP III-2005 criteria, respectively. RAR profiles, including rhythmic strength (RA), were assessed using wrist-worn actigraphy (mean valid days: 6.7; mean recording time: 22.83 h/day) and categorized into tertile groups (low/medium/high). Cox proportional-hazards models were conducted to predict all-cause mortality risk, and presented in hazard ratio (HR) with 95% confidence intervals (CI). <b>Results:</b> Frailty and low RA significantly predicted mortality risk [HR (95% CI); <i>Frailty</i>: 1.71 (1.11-2.62); <i>Low RA</i>: 1.46 (1.14-1.87)]. Upon stratified analyses, significant associations of frailty and low RA with mortality were observed exclusively among individuals with MetS [HR (95% CI); <i>Frailty</i>: 1.89 (1.17-3.03); <i>Low RA</i>: 1.49 (1.14-1.61)]. <b>Conclusion:</b> Frailty and disrupted RAR are independent short-term predictors of mortality, particularly in individuals with MetS. The coexistence of MetS, frailty, and low RA amplifies mortality risk, highlighting their importance as critical markers of vulerability in older adults.