Abstract

Studies examining the relationships between chronic inflammation, cognitive function and cognitive decline in older adults have yielded conflicting results. In a large cohort of older adults free from established dementia (n = 3270; 73.1 ± 7.9 years; 68.4% female), we evaluated the cross-sectional and longitudinal relationships between serum cytokines (IL-6, IL-10, TNF-α) and both global and domain-specific cognitive performance (Repeatable Battery for Assessment of Neuropsychological Status [RBANS]). Higher IL-6 (OR: 1.33; 1.06, 1.66, p = 0.01), TNF-α (OR: 1.35; 1.09, 1.67, p = 0.01) and IL-6:IL-10 Ratio (OR: 1.43; 1.17, 1.74, p = 0.001) were cross-sectionally associated with impaired global RBANS performance. For specific cognitive domains, greatest effect sizes were observed between higher TNF-α levels and poorer visual-spatial and attention performance. In a subset of participants (n = 725; 69.8 ± 5.5 years; 67.0% female) with repeat assessment performed at a median of 5.4 years, only higher baseline IL-6:IL-10 ratio was associated with impaired incident overall, immediate memory and visual-spatial performance. Associations were stronger in females, but not modified by age or APOE genotype.

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