Associations among cognitive performance, VCAM-1, and GFAP in black adults: The ARCHES study

Astrocytic injury and endothelial activation are interconnected processes within the neurovascular system that may contribute to variability in cognitive performance among cognitively unimpaired adults. Glial fibrillary acidic protein (GFAP) reflects astrocytic injury, while vascular cell adhesion molecule-1 (VCAM-1) reflects systemic endothelial activation. We examined whether VCAM-1 modifies associations between GFAP and cognition in cognitively unimpaired Black adults. This cross-sectional analysis included 313 Black adults aged ≥ 45 years enrolled in the Aging Research Characterizing Health Exposome via Social Drivers (ARCHES) study. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC) as the primary outcome and the Montreal Cognitive Assessment (MoCA) as a secondary outcome. Plasma GFAP and VCAM-1 were quantified using ultrasensitive immunoassays (NULISA™; Alamar Biosciences). Gaussian generalized linear models tested main effects and a VCAM-1 × GFAP interaction, adjusting for age, sex, and years of education; sensitivity analyses additionally adjusted for the Area Deprivation Index (ADI), body mass index (BMI), and apolipoprotein E (APOE) ε4 genotype. VCAM-1 and GFAP did not show independent associations with PACC; however, the VCAM-1 × GFAP interaction was significant (β = -1.36 × 10⁻⁶, 95% CI: -2.43 × 10⁻⁶ to -2.94 × 10⁻⁷, p = 0.013; FDR p = 0.030; standardized β = -0.118) and remained significant after additional adjustment for ADI, BMI, and APOE ε4 status. Associations were not significant for MoCA. These findings suggest that VCAM-1 may modify the relationship between GFAP and cognitive performance in cognitively unimpaired Black adults.