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.
7 affiliations
- 1Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, United States.
- 2Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.
- 3Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
- 4Department of Psychology, Georgia State University, Atlanta, GA, United States.
- 5Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States.
- 6Department of Neurology, Harvard Medical School, Boston, MA, United States.
- 7Gerontology Institute, Georgia State University, Atlanta, GA, United States.
Abstract
Systemic 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. Participants 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. Higher 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. Plasma 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.
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BibTeX
@article{misiura2026plasma,
title = {{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.}},
author = {Maria B Misiura and Tammy O Joseph and Jessica A Cooper and Gabi Champion and Jennalyn Burnette and Alex Bartlett and Kyle Thatcher and Nadine Ciera Austin and Vonetta M Dotson},
journal = {Frontiers in dementia},
year = {2026},
month = oct,
doi = {10.3389/frdem.2026.1930196},
url = {https://europepmc.org/article/MED/42952734},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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.
AU - Maria B Misiura
AU - Tammy O Joseph
AU - Jessica A Cooper
AU - Gabi Champion
AU - Jennalyn Burnette
AU - Alex Bartlett
AU - Kyle Thatcher
AU - Nadine Ciera Austin
AU - Vonetta M Dotson
PY - 2026
DA - 2026/10/14
JO - Frontiers in dementia
DO - 10.3389/frdem.2026.1930196
UR - https://europepmc.org/article/MED/42952734
AB - Systemic 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. Participants 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. Higher 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. Plasma 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.
SN - 2813-3919
ER -