Subjective well-being and allostatic load in multimorbidity transitions: A multi-state survival analysis of three international longitudinal cohorts.

BACKGROUND: Physical-psychological-cognitive multimorbidity (PPC-MM) is a critical challenge in aging. The distinct and combined roles of physiological dysregulation (allostatic load, AL) and psychological state (subjective well-being, SWB) in driving PPC-MM transitions remain unclear. This study investigates how AL and SWB independently and jointly influence multimorbidity progression across three national cohorts.

METHODS: We harmonized data from the Health and Retirement Study (US), English Longitudinal Study of Aging (UK), and China Health and Retirement Longitudinal Study (CHARLS), comprising 5629 adults aged ≥45 free of baseline PPC-MM. AL was derived from cumulative biomarkers; SWB was standardized across cohorts. Multi-state survival models estimated hazard ratios (HRs) for transitions to physical-psychological (P1P2), physical-cognitive (P1C), psychological-cognitive (P2C), and triple (P1P2C) multimorbidity.

RESULTS: High AL increased overall PPC-MM risk (HR = 1.66, 95% CI: 1.16-2.38), specifically driving transitions involving cognitive decline (None→P1C: HR = 1.48). Conversely, low SWB acted as a broad risk factor, strongly predicting physical-psychological onset (None→P1P2: HR = 2.14). Notably, the combination of high AL and low SWB tripled the risk of developing complex multimorbidity (None→P1P2C: HR = 3.23). Meta-analysis confirmed high consistency across cohorts.

CONCLUSIONS: Low SWB functions as a generalized driver of multimorbidity, whereas high AL specifically accelerates cognitive pathways. Their combined presence creates a high-risk profile for complex multimorbidity. Effective prevention requires integrating physiological management with psychological support to mitigate these distinct but compounding pathways.