Longitudinal associations between multimodal symptom clusters and functional disability in older adults: a...

Functional disability is a rising global concern in aging societies, yet little is known about how co-occurring symptoms such as pain, sleep disturbances, and depressive mood jointly contribute to its development across diverse populations. This study aimed to examine the longitudinal associations between multimodal symptom clusters and incident functional disability using harmonized data from three culturally distinct cohorts in Europe (SHARE, ELSA) and East Asia (KLoSA). We analyzed harmonized data from 33,766 functionally independent adults aged ≥50 years from the SHARE, ELSA, and KLoSA. Symptom clusters were defined as baseline pain, sleep disturbance, and depressive moods. Cox models estimated disability risk, Sankey plots visualized symptom-function transitions, and mediation analyses explored indirect pathways. Multi-symptom clusters showed a graded dose-response association with functional decline, with triple-symptom groups conferring the highest risk (HR=2.36). Pain and sleep disturbance were the strongest predictors. Longitudinally, symptom clusters exhibited dynamic yet patterned trajectories-including persistence, progression, and partial reversal-highlighting early windows for intervention. Mediation analyses revealed reciprocal indirect effects between pain and sleep, whereas joint exposure resulted in pathway suppression. This is the first multinational study to systematically examine symptom cluster-disability pathways across culturally distinct cohorts. These findings underscore the predictive value and temporal dynamics of symptom combinations and support their use in global aging surveillance and targeted geriatric prevention strategies.