The Cross-sectional and longitudinal associations between il-6, il-10, and TNFα and cognitive outcomes in the mayo clinic study of aging

Background: Chronic inflammation has been linked with geriatric-related conditions, including dementia. Inflammatory cytokine levels, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) α, in the blood have been associated with cognitive impairment and decline. However, evidence has been mixed. Methods: We examined the cross-sectional and longitudinal associations between baseline-measured IL-6, IL-10, and TNFα levels and the ratio of IL-6/IL-10 with cognitive test performance and mild cognitive impairment (MCI) among 1,602 community-dwelling older adults (median age = 72.8) enrolled in the Mayo Clinic Study of Aging. Approximately half (46.5%) of participants were female and 98.6% were white. At baseline and follow-up visits (occurring at 15-month intervals), participants completed neuropsychological testing, blood draws, and had a clinical consensus diagnosis. Results: In multivariable cross-sectional analyses, we did not observe an association between inflammatory cytokine levels and global or domain-specific cognitive z scores; however, higher IL-6 and IL-10 levels were associated with greater odds of a MCI diagnosis. Longitudinally, we did not observe any association between inflammatory cytokine levels and cognitive test performance or risk of MCI. Sex, age, cognitive status, APOE ϵ4 genotype, diabetes, depression, and cerebral amyloid-beta deposition were not effect modifiers. Conclusions: These results suggest that plasma inflammatory markers may not be useful to ascertain risk for cognitive decline and MCI in the general population.