Peripheral inflammation and cognition in older adults with and without cognitive impairment

Background Understanding how different inflammatory markers relate to cognition is important for the development of therapeutic targets in Alzheimer’s disease (AD). However, many studies have relied on a single, broad measure of inflammation or a select handful of markers that have been identified in the AD literature. We examined a large set of plasma inflammatory markers that were statistically grouped via principal component analysis (PCA). Associations between inflammation component scores and cognition were examined. Method Participants included 41 cognitively normal (CN) and 64 cognitively impaired (CI; 47 mild cognitive impairment and 17 AD) older adults from the Center for Neurodegeneration and Translational Neuroscience. Composite scores for memory, executive functioning, processing speed, and language were created by averaging age‐adjusted z scores for two tests per domain. Plasma levels of inflammatory cytokines were measured using the Luminex platform and Biorad 48‐plex cytokine assay. Five markers with null values were excluded, and the remaining markers were included in a PCA. Relationships between the inflammation component scores and cognition were examined using linear regression models with inflammatory marker as the predictor and each cognitive composite separately as the dependent variable, with adjustment for education, sex, and clinical diagnosis (CN vs CI). Result The PCA produced a 7‐component solution that accounted for 75% of the variance. In the final models, Components 2 (β = 0.260, p = 0.020) and 4 (β = 0.235, p = 0.036) were positively associated with memory, Components 2 (β = 0.231, p = 0.052), 4 (β = 0.260, p = 0.031), and 6 (β = 0.280, p = 0.016) were positively associated with executive functioning, and Components 2 (β = 0.221, p = 0.032) and 4 (β = 0.283, p = 0.007) were positively associated with processing speed. Inflammatory components were not significantly related to language. Conclusion Higher levels of peripheral inflammatory cytokines were associated with better memory, executive functioning, and processing speed in older adults, even when accounting for clinical diagnosis. Acute elevations of certain inflammatory markers may be associated with a protective role in cognitive aging. Longitudinal research examining stability of cytokine levels and association with cognition in AD trajectories is needed.