Frailty Modifies the Association Between Multimorbidity and Hospital-Associated Disability in Hospitalized Older Adults

Objectives To examine whether the prognostic relevance of multimorbidity burden for hospital-associated disability (HAD) varies with baseline frailty in hospitalized older adults. Design Retrospective multicenter cohort study. Setting and Participants We analyzed data from 1599 older adults aged ≥65 years admitted to acute care hospitals in Japan between October 2019 and March 2025. After exclusions, 1299 individuals formed the final analytic cohort. Methods Comorbidity burden was assessed using the Charlson Comorbidity Index (CCI). Frailty was categorized using the Clinical Frailty Scale into nonfrail (≤3), mildly frail (4), and frail (≥5). HAD was defined as a decline of at least 5 points in the Barthel Index during hospitalization. Multivariable logistic regression models, including an interaction term between CCI and frailty, were used, adjusted for age, sex, and cognitive function. Results Higher CCI was associated with higher odds of HAD in the nonfrail group [odds ratio (OR), 1.44; 95% CI, 1.20-1.73], but this association was attenuated in the mildly frail group (OR, 1.11; 95% CI, 0.91-1.35) and was not observed in the frail group (OR, 0.98; 95% CI, 0.90-1.06). The interaction between CCI and frailty was statistically significant ( P for interaction <.001). Conclusions and Implications The prognostic relevance of multimorbidity diminishes with increasing frailty, suggesting a loss of risk discrimination at higher levels of physiological vulnerability. These findings highlight the importance of integrating frailty into risk stratification frameworks and support a shift toward resilience-based approaches in the management of hospitalized older adults.