Frailty progression: The role of multimorbidity configurations in frailty transitions and predicting mortality risk among older adults

BACKGROUND: Different patterns of non-communicable diseases (NCDs) in older adults may lead to distinct transitions of frailty progression and mortality risk. This study aimed to determine whether specific multimorbidity patterns of configurations (MCs) are associated with differences in frailty transitions and mortality risk. METHODS: Longitudinal data from 14,511 adults aged ≥ 60 years in the Lifelines cohort were analyzed, with median follow-up of 3.8 years for frailty and 5.6 years for mortality. Multimorbidity was assessed both by accumulation (≥ 2 NCDs) and by MCs previously identified through latent class analysis. Frailty was measured using a 32-item index and categorized as robust, pre-frail, or frail. Multistate Markov models estimated transitions between frailty states and to death; mixed-effects models assessed frailty average-changes over time. RESULTS: The prevalence of multimorbidity by NCD accumulation increased monotonically with frailty, whereas the distribution of MCs varied across frailty categories. The type of multimorbidity influenced the risk of transitioning between frailty states and to death. The 'Complex Treatment' group had the highest baseline frailty. The 'Major CVD & Vascular' and 'Heart & Vascular' configurations showed the steepest increases in frailty, while the 'Vascular' and 'Metabolic' groups presented lower frailty levels and a higher likelihood of recovery. Participants in the 'CVD & Vascular' group were more likely to transition from pre-frailty or frailty to death compared to other configurations. CONCLUSIONS: Frailty transitions and mortality risk varied across MCs, identifying moderate- and high-risk profiles. MCs provide a more detailed interpretation of into how multimorbidity shapes frailty and mortality than simple disease accumulation.