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Objectives To quantify associations between inflammatory biomarkers and hippocampal volume ( HV) and to examine effect modification according to sex, race, and age. Design Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized β-coefficients adjusted for age, sex, race, and education. Setting Community cohorts in Jackson, Mississippi and Rochester, Minnesota. Participants The Genetic Epidemiology Network of Arteriopathy study. Measurements C-reactive protein ( CRP), interleukin-6 ( IL-6), and soluble tumor necrosis factor receptors 1 ( sTNFR-1) and 2 ( sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. Results In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation ( SD) increase in sTNFR-1 was associated with 59.1 mm3 (95% confidence interval ( CI) = −101.4 to −16.7 mm3) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm3 (95% CI = −92.2 to −5.3 mm3) smaller HV. Relationships were stronger for sTNFR-2 in men ( HV = −116.6 mm3 for each SD increase, 95% CI = −201.0 to −32.1) than women ( HV = −26.0 per SD increase, 95% CI = −72.4-20.5) and sTNFR-1 in non-Hispanic whites ( HV = −84.7 mm3 per SD increase, 95% CI = −142.2 to −27.1) than African Americans ( HV = −14.1 mm3 per SD increase, 95% CI = −78.3-50.1). Associations between IL-6 or CRP and HV were not supported. Conclusion Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities ( WMHs) in African Americans ( AAs) and European Americans ( EAs). Design Cross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios ( ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle-brachial index, race (site), and supported interactions. Setting Genetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort. Participants AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26-91, 50% obese, 72% hypertensive). Measurements Inflammation (C-reactive protein ( CRP), interleukin-6 ( IL6), soluble tumor necrosis factor receptors ( sTNFRs) 1 and 2, WMH volume (cm3) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile). Results In separate models, inflammatory markers were associated with walking speed ( sTNFR1: β = −2.74, P < .001; sTNFR2: β = −1.23, P = .03; CRP: β = −1.95, P = .001; IL6: β = −1.24, P = .03) and mobility difficulty ( sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = −3.17, P = .02) but not with mobility difficulty ( OR = 1.10, P = .54). Adjusting for WMH did not change associations. Conclusion In young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs. [ABSTRACT FROM AUTHOR]