Nonlinear Associations Between Frailty and Medication Burden in Hospitalized Older Adults

To examine how medication burden varies across frailty stages in hospitalized older adults, with a focus on potential nonlinear associations: METHODS: We analyzed a multicenter cohort of hospitalized adults aged ≥ 65 years. Frailty was assessed using the preadmission Clinical Frailty Scale (CFS). Associations between CFS and total medication count, potentially inappropriate medication (PIM) count, and anticholinergic burden (Japanese Anticholinergic Risk Scale) were evaluated using restricted cubic spline models adjusted for age, sex, and Charlson Comorbidity Index. Primary analyses were conducted in participants with complete data (n = 1075).

CFS showed significant associations with all medication-related indicators (all overall p < 0.05), with evidence of nonlinearity for medication count (p < 0.0001) and PIM count (p = 0.024). Medication burden increased with worsening frailty, with the steepest rise observed in moderate frailty, followed by attenuation in more severe frailty. Across all indicators, adjusted curves suggested a consistent transition around CFS 5-6. These patterns were independent of age, sex, and comorbidity burden.

Medication burden is strongly and nonlinearly associated with frailty in hospitalized older adults. These stage-dependent patterns suggest that moderate frailty may represent a window for targeted medication review and deprescribing, supporting frailty-stratified approaches to medication management in acute care.