Plasma IL-6 as a shared inflammatory marker of cognitive impairment across racially and ethnically diverse older adults: matched analyses from the HABS-HD study

BackgroundSystemic inflammation is implicated in cognitive aging, yet whether interleukin-6 (IL-6) represents a shared versus group-specific marker of cognitive impairment across racially and ethnically diverse older adults remains unclear. This study examined associations among depressive symptoms, plasma IL-6, and cognitive impairment while testing mediation and ethnoracial moderation.MethodsParticipants were drawn from the Health and Aging Brain Study–Health Disparities (HABS-HD). In the full multi-ethnic complete-case sample (N = 2,187; 963 non-Hispanic White, 277 Black, and 947 Hispanic participants), logistic regression models tested the association of log₁₀-transformed plasma IL-6 with binary cognitive impairment (mild cognitive impairment or dementia versus cognitively unimpaired status), adjusting for age, education, sex, Geriatric Depression Scale (GDS) total score, ethnoracial group, and APOE ε4 carrier status. Parallel models examined GDS–cognitive impairment associations. Mediation models tested whether IL-6 statistically mediated the association between GDS scores and cognitive impairment. Moderation analyses tested IL-6 × ethnoracial group interactions. Sensitivity analyses repeated the main-effect, interaction, and mediation models in 1:1 matched Black/White (N = 554) and Hispanic/White (N = 794) subsamples that were matched exactly on sex and cognitive status and balanced on age and education.ResultsHigher plasma IL-6 was associated with greater odds of cognitive impairment in the full sample (OR = 1.87, 95% CI [1.31, 2.68], p < 0.001), and this association did not significantly differ by ethnoracial group (χ2 = 3.52, df = 2, p = 0.172). Higher GDS scores were also independently associated with cognitive impairment (OR = 1.06 per point, 95% CI [1.04, 1.08], p < 0.001). IL-6 statistically mediated a small proportion of the GDS–cognitive impairment association (indirect effect = 0.0025, Sobel p = 0.014). The IL-6 association remained significant in the Black/White (OR = 2.62, 95% CI [1.27, 5.46], p = 0.009) and Hispanic/White (OR = 2.24, 95% CI [1.27, 3.97], p = 0.005) matched samples, with no significant matched-sample IL-6 × ethnoracial group interactions.ConclusionPlasma IL-6 emerged as a consistent inflammatory correlate of cognitive impairment across Black, Hispanic, and non-Hispanic White older adults. The findings support IL-6 as a potentially generalizable biomarker while highlighting the need for longitudinal studies to clarify its role in depression-related cognitive decline in diverse populations.