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

INTRODUCTION: Few studies have investigated how neuroinflammation early in the disease course may affect Alzheimer's disease (AD) progression over time despite evidence that neuroinflammation is associated with AD. METHODS: Research participants with cerebrospinal fluid (CSF) biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in this study. Cox models were used to investigate whether baseline CSF neuroinflammation was associated with incident mild cognitive impairment (MCI) or AD. Moderating effects of sex and apolipoprotein E (APOE) ε4 were also examined. RESULTS: Elevated levels of tumor necrosis factor α (TNF‐α), interleukin (IL)‐9, and IL‐12p40 at baseline were associated with higher rates of conversion to MCI/AD. Interactions with sex and APOE ε4 were observed, such that women with elevated TNF‐α and all APOE ε4 carriers with elevated IL‐9 levels had shorter times to conversion. In addition, TNF‐α mediated the relationship between elevated IL‐12p40 and IL‐9. DISCUSSION: Elevated neuroinflammation markers are associated with incident MCI/AD, and the factors of sex and APOE ε4 status modify the time to conversion.