The mean age of the 1238 participants was 76.2 years (SD = 4.3); 63.7% were female. Their initial four-domain IC scores averaged 78.9 points (SD = 9.3), with a yearly decline of 1.17 points (95% CI = À1.30 to À1.05; P < 0.001). We observed significant associations of lower baseline IC with higher CRP, IL-6, TNFR-1 and GDF-15, after controlling age, sex, MAPT group allocation and educational level [CRP: adjusted β (95% CI) = À1.56 (À2.64 to À0.48); P = 0.005; IL-6: adjusted β = À3.16 (À4.82 to À1.50); P < 0.001; TNFR-1: adjusted β = À6.86 (À10.25 to À3.47); P < 0.001; GDF-15: adjusted β = À7.07 (À10.02 to À4.12); P < 0.001]. Higher TNFR-1, MCP-1 and GDF-15 were associated with faster decline in four-domain IC over 4 years [TNFR-1: adjusted β (95% CI) = À1.28 (À2.29 to À0.27); P = 0.013; MCP-1: adjusted β = À1.33 (À2.24 to À0.42); P = 0.004; GDF-15: adjusted β = À1.42 (À2.26 to À0.58); P = 0.001]. None of the biomarkers was significantly associated with the five-domain IC decline. Conclusions Inflammation was associated with lower IC in older adults. Among all plasma biomarkers, TNFR-1 and GDF-15 were consistently associated with IC at the cross-sectional and longitudinal levels.