Association of intrinsic capacity with functional decline and mortality in older adults: a systematic review and meta-analysis of longitudinal studies

Background: Together with environmental factors, intrinsic capacity (the composite of all the physical and mental capacities of an individual) has been proposed as a marker of healthy ageing. However, whether intrinsic capacity predicts major clinical outcomes is unclear. We aimed to explore the association of intrinsic capacity with functional decline and mortality in older adults. Methods: In this systematic review and meta-analysis, we conducted a systematic search in MEDLINE (via PubMed), Scopus, and Web of Science from database inception to Feb 14, 2024, of observational longitudinal studies conducted in older adults (age ≥60 years) assessing the association of intrinsic capacity with impairment in basic activities of daily living (BADL) or instrumental activities of daily living (IADL) or risk of mortality. Estimates were extracted by two reviewers (JLS-S and W-HL) and were pooled using three-level meta-analytic models. The quality of each study was independently assessed by two authors (JLS-S and PLV) using the Newcastle–Ottawa Scale for longitudinal studies. Heterogeneity was evaluated using the I² indicator at two levels: within-study (level 2) and between-study (level 3) variation. For associations between intrinsic capacity and IADL and BADL, we transformed data (standardised β coefficients and odds ratios [ORs]) into Pearson product moment correlation coefficients (r) using Pearson and Digby formulas to allow comparability across studies. For associations between intrinsic capacity and risk of mortality, hazard ratios (HRs) with 95% CIs were extracted from survival analyses. This study is registered with PROSPERO, CRD42023460482. Findings: We included 37 studies (206 693 participants; average age range 65·3–85·9 years) in the systematic review, of which 31 were included in the meta-analysis on the association between intrinsic capacity and outcomes; three studies (2935 participants) were included in the meta-analysis on the association between intrinsic capacity trajectories and longitudinal changes in BADL or IADL. Intrinsic capacity was inversely associated with longitudinal impairments in BADL (Pearson's r –0·12 [95% CI –0·19 to –0·04]) and IADL (–0·24 [–0·35 to –0·13]), as well as with mortality risk (hazard ratio 0·57 [95% CI 0·51 to 0·63]). An association was also found between intrinsic capacity trajectories and impairment in IADL (but not in BADL), with maintained or improved intrinsic capacity over time associated with a lower impairment in IADL (odds ratio 0·37 [95% CI 0·19 to 0·71]). There was no evidence of publication bias (Egger's test p>0·05) and there was low between-study heterogeneity (I²=18·4%), though within-study (I²=63·2%) heterogeneity was substantial. Interpretation: Intrinsic capacity is inversely associated with functional decline and mortality risk in older adults. These findings could support the use of intrinsic capacity as a marker of healthy ageing, although further research is needed to refine the structure and operationalisation of this construct across settings and populations. Funding: None. Translations: For the Spanish and French translations of the abstract see Supplementary Materials section.