Inflammatory Cytokines and Cognition in Alzheimer's Disease and Its Prodrome

Objective The aim of this study was to investigate the association between blood levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Methods Peripheral concentration of TNF-alpha and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. Results The 37 participants included 8 patients with Alzheimer's disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-alpha and IL-6 levels were higher in patients with AD than in healthy controls. TNF-alpha levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-alpha and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-alpha level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-alpha level and the z-score on Word List Learning remained significant when age was adjusted. Conclusion The difference in the blood levels of TNF-alpha and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-alpha levels were associated with worse immediate memory performance, even after adjusting for age.