Higher baseline levels of CSF inflammation increase risk of incident mild cognitive impairment and Alzheimer’s disease dementia

Background Few studies have investigated how inflammation early in the disease course may affect AD progression over time despite converging evidence that elevated levels of inflammation are associated with AD in cross-sectional studies. Methods Two-hundred ninety-two research participants with CSF biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included in this study. Cox proportional hazards models were used to investigate whether baseline levels of inflammatory CSF markers were associated with incident mild cognitive impairment or AD and time to conversion. Potential moderating effects of sex and APOE4 were also examined. Results Elevated levels of pro-inflammatory markers TNF-α, IL-9, and IL-12p40 at baseline were associated with higher rates of conversion to MCI/AD. Interactions with sex and APOE4 were observed, such that women with elevated TNF- α and all APOE4 carriers with elevated IL-9 levels had shorter times to conversion. Additionally, TNF-α mediated the relationship between elevated IL-12p40 and IL-9. Conclusion Elevated inflammation markers are associated with incident MCI or AD, and the factors of sex and APOE4 status modify the time to conversion.