Hidden multistate models to study multimorbidity trajectories

V Valentina Manzoni F Francesca Ieva A Amaia Calderón-Larrañaga D Davide Liborio Vetrano C Caterina Gregorio

Abstract

Abstract Multimorbidity in older adults is common, heterogeneous, and highly dynamic, and it is strongly associated with disability and increased healthcare utilization. However, existing approaches to studying multimorbidity trajectories are largely descriptive or rely on discrete-time models, which struggle to handle irregular observation intervals and right-censoring. We developed a continuous-time hidden multistate modeling framework to capture transitions among latent multimorbidity patterns while accounting for interval censoring and misclassification. A simulation study compared alternative model specifications under varying sample sizes and follow-up schemes, and the best-performing specification was applied to longitudinal data from the Swedish National study on Aging and Care–Kungsholmen (SNAC-K), including 2716 multimorbid participants followed for up to 18 years. Simulation results showed that hidden multistate models substantially reduced bias in transition hazard estimates compared to non-hidden models, with fully time-inhomogeneous models outperforming piecewise approximations. Application to SNAC-K confirmed the feasibility and practical utility of this framework, enabling identification of risk factors for accelerated progression toward complex multimorbidity and revealing a gradient of mortality risk across patterns. Continuous-time hidden multistate models provide a robust alternative to traditional approaches, supporting individualized predictions and informing targeted interventions and secondary prevention strategies for multimorbidity in aging populations.

Article Details

Volume / Issue Vol. 16, Issue 1
Published July 31, 2026
ISSN 2045-2322
Publisher Nature Portfolio

Journal Info

Scientific Reports

Nature Portfolio

ISSN: 2045-2322 Open Access Life Sciences

Authors (5)

V

Valentina Manzoni

F

Francesca Ieva

A

Amaia Calderón-Larrañaga

D

Davide Liborio Vetrano

C

Caterina Gregorio