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<p>Intrinsic capacity (IC) reflects multidomain functional reserve and a measurable phenotype of healthy ageing, but its biological correlates remain incompletely understood. We examined associations of neurofilament light chain (NfL), CXCL9 and inflammatory biomarkers with IC in community-dwelling older adults. We conducted a cross-sectional analysis within the Screening and Prevention of Intrinsic Capacity Decline in Elders (SPICE) programme. IC was derived from locomotion (SPPB), cognition (MoCA), psychological health (PHQ-9), and vitality (MNA-SF), rescaled to a 0–100 composite and analysed as both z scores and tertiles. NfL, CXCL9, and TNFRSF11B were measured using Olink assays, and interleukin-6 (Il-6) by electrochemiluminescence. Multivariable linear and multinomial regression models assessed associations with IC. Mediation analyses evaluated indirect effects of inflammatory biomarkers via NfL. Among 199 participants (mean age 71.9 ± 5.2&#xa0;years), NfL, CXCL9, IL-6, and TNFRSF11B increased across decreasing IC tertiles. In multivariate models, only NfL remained independently associated with IC (β − 0.41, 95% CI − 0.72 to − 0.12), with attenuation of other biomarkers after NfL adjustment. Higher NfL was associated with increased likelihood of low versus high IC (RRR 6.62, 95% CI 1.84–23.76). Mediation analyses showed significant indirect effects via NfL for CXCL9 (27.6%) and TNFRSF11B (53.9%), but not IL-6. Domain-specific analyses indicated distinct biomarker associations: NfL with locomotion and psychological health, IL-6 with locomotion, CXCL9 with vitality and TNFRSF11B with cognition. NfL was significantly associated with IC and partially mediated inflammatory associations. Integrating blood-based biomarkers with IC assessment may enhance early detection of multidomain vulnerability in ageing.</p>

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Association of neurofilament light chain, CXCL9, IL-6, and TNFRSF11B with intrinsic capacity in community-dwelling older adults

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Reshma Aziz Merchant,
  • Yang Liu,
  • Benjamin Y. Q. Tan,
  • Ching-Hui Sia,
  • Andrea Wong,
  • Li Feng Tan,
  • Gustavo Duque,
  • Hidenori Arai,
  • Bruno Vellas,
  • Jean Woo

摘要

Intrinsic capacity (IC) reflects multidomain functional reserve and a measurable phenotype of healthy ageing, but its biological correlates remain incompletely understood. We examined associations of neurofilament light chain (NfL), CXCL9 and inflammatory biomarkers with IC in community-dwelling older adults. We conducted a cross-sectional analysis within the Screening and Prevention of Intrinsic Capacity Decline in Elders (SPICE) programme. IC was derived from locomotion (SPPB), cognition (MoCA), psychological health (PHQ-9), and vitality (MNA-SF), rescaled to a 0–100 composite and analysed as both z scores and tertiles. NfL, CXCL9, and TNFRSF11B were measured using Olink assays, and interleukin-6 (Il-6) by electrochemiluminescence. Multivariable linear and multinomial regression models assessed associations with IC. Mediation analyses evaluated indirect effects of inflammatory biomarkers via NfL. Among 199 participants (mean age 71.9 ± 5.2 years), NfL, CXCL9, IL-6, and TNFRSF11B increased across decreasing IC tertiles. In multivariate models, only NfL remained independently associated with IC (β − 0.41, 95% CI − 0.72 to − 0.12), with attenuation of other biomarkers after NfL adjustment. Higher NfL was associated with increased likelihood of low versus high IC (RRR 6.62, 95% CI 1.84–23.76). Mediation analyses showed significant indirect effects via NfL for CXCL9 (27.6%) and TNFRSF11B (53.9%), but not IL-6. Domain-specific analyses indicated distinct biomarker associations: NfL with locomotion and psychological health, IL-6 with locomotion, CXCL9 with vitality and TNFRSF11B with cognition. NfL was significantly associated with IC and partially mediated inflammatory associations. Integrating blood-based biomarkers with IC assessment may enhance early detection of multidomain vulnerability in ageing.