Background: Chronic systemic inflammation has been positively associated with structural and functional brain changes representing early markers of Alzheimer's Disease (AD) and cognitive decline. The current study examined associations between systemic inflammation and cognitive performance among African-Americans and Whites urban adults.

Methods: Participants were selected from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (2004-2013, baseline age: 30-64 y, mean ± SD follow-up time of 4.64 ± 0.93 y, N = 189-222, k = 1.5-1.7 observations/participant). Cytokines known to be positively linked to AD incidence among others were tested against cross-sectional and longitudinal cognitive function, stratifying by age group (≤50 y vs. >50 y), sex and race. A series of mixed-effects regression models were conducted, adjusting for key confounders.

Results: Among key findings, IL1β was positively associated with a faster rate of decline on a test of executive functioning, among older adults (age >50 y, γ₁₁ = +2.49 ± 0.89, p = 0.005), while in the total population, IL-6 was linked to a faster decline on a test of verbal memory (γ₁₁ = -0.011 ± 0.004, p = 0.009). Among younger participants, IL-18 was linked to a poorer performance on a test of attention at baseline (age ≤50 y, γ₀₁ = -0.007 ± 0.0025, p = 0.004) though a slower rate of decline with higher IL-18 was detected for a test of psychomotor speed in older adults (age >50 y, γ₁₁ = +0.0010 ± 0.0004, p = 0.008). Finally, among Whites, unlike among African-Americans, IL-6 was associated with a better baseline performance on two tests of verbal and working memory.

Conclusions: Cytokines were shown to be associated with age-related cognitive decline among middle-aged and older urban adults in an age group and race-specific manner. Further longitudinal studies are needed to replicate our findings and mediation through relevant biological and psychosocial factors need to be studied as well.