Intrinsic capacity as a predictor of depression onset in middle-aged and older adults: Insights from the UK Biobank

BACKGROUND: Intrinsic capacity (IC), defined as an individual's overall physical and mental capabilities, is central to healthy aging. It is, however, less clear to what degree there is an association between IC and the onset of depressive symptoms. METHODS: We analyzed the data of 426,714 participants enrolled in the UK Biobank. The variation in sample size (range: 398,775-414,232) reflects differences across specific domain-level data completeness. Seven biomarkers reflecting functional ability across the five IC domains were used to compute a composite IC score ranging from 0 (optimal IC) to +4 (most impaired IC). The associations between IC scores and incident depressive disorders were also assessed. RESULTS: After a median follow-up of 10.6 years (cutoff date: December 31, 2022), 42,537 new cases of psychiatric disorders were recorded, of which 13,464 (31 %) were attributed primarily to depression. A progressive increase in the prevalence of individual IC impairments was observed along with the rising incidence of depression. In multivariable models, higher IC scores were significantly associated with an increased risk of depression: hazard ratio (HR) [95 % confidence interval (CI)] of 3.91 (3.44-4.45) in men (C-index = 0.66) and 3.94 (3.57-4.35) in women (C-index = 0.66). These associations were confirmed using sensitivity analysis. As this was an observational study, reverse causality cannot be ruled out. CONCLUSIONS: Higher IC impairment scores are associated with an elevated risk of developing depressive disorders. While causality cannot be inferred, the measure of IC may be used to identify individuals who are at higher risk, and to guide early, targeted preventive strategies.