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

Authors

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

Published in

GeroScience. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

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.

PMID:
42550369
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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