Abstract
Background
Systemic inflammation has been implicated in cognitive aging and neurodegeneration; however, inflammatory biomarkers are expressed in coordinated patterns rather than as isolated markers.
Objective
To identify latent inflammatory biomarker groupings and evaluate their associations with cognitive performance among midlife and older adults.
Methods
This cross-sectional study included 334 participants from the Aging Research Characterizing Health Exposome via Social Drivers (ARCHES) study. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma inflammatory biomarkers were quantified using the NuLISA™ multiplex immunoassay platform. Exploratory factor analysis (EFA) (minimum residual extraction, oblimin rotation) identified latent inflammatory factors, retaining biomarkers with loadings ≥0.40. Factor scores were evaluated in multivariable linear regression models adjusted for age, sex, education, and genotype status; sensitivity analyses adjusted for socioeconomic context, medication use, BMI, lifestyle factors, and clinical diagnoses. Age-stratified and nonlinear spline analyses were conducted.
Results
27 of 43 biomarkers formed an eight-factor structure explaining 43% of variance. Two factors were significantly associated with cognitive performance after FDR correction. Factor 4 (CCL4, CXCL1, S100A12) and Factor 5 (IL2, IL5, IL13, IL10, CSF2) were inversely associated with PACC scores. These associations remained consistent across sensitivity analyses. Age-stratified analyses showed that several inflammatory factors were associated with cognitive performance among participants aged 45–<65 years, whereas no factors remained significant among participants aged ≥65 years after FDR correction. Nonlinear modeling indicated a non-linear age-cognitive performance relationship.
Conclusions
EFA identified clusters of correlated inflammatory biomarkers associated with cognitive performance in this cohort of midlife and older adults.
Authors and Affiliations
Ramkrishna K. Singh¹, Semere Bekena¹, Alexis I.B. Walker¹, Kaylin Taylor¹, Yiqi Zhu¹, Subrata Pal¹, Essa A. Mohamed², Jean-Francois Trani³,⁴,⁵, Ian Kaplan⁶, and Ganesh M. Babulal¹,²,⁶
¹ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
² Departments of Neurology and Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
³ School of Public Health, Washington University in St. Louis, St. Louis, MO, USA
⁴ Interdisciplinary Laboratory of Economic Sociology, National Conservatory of Arts and Crafts, Paris, France
⁵ Department of Psychology, University of Johannesburg, Johannesburg, South Africa
⁶ Norwegian Afghanistan Committee, Kabul, Afghanistan