Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults

Background: Converging animal findings suggest that higher peripheral levels of inflammation are associated with activation of central inflammatory mechanisms that result in hippocampal neurodegeneration and related impairment of memory function. We have recently shown, consistent with animal findings, an inverse association between peripheral levels of interleukin-6 (IL-6), a relatively stable marker of systemic inflammation, and memory function in mid-life adults. In the current study, we extend this work to test whether systemic inflammation is associated with reduced grey matter volume of the hippocampus. Methods: For this purpose, we used a computational structural neuroimaging method (optimized voxel-based morphometry) to evaluate the relationship between plasma IL-6 levels and hippocampal grey matter volume in a sample of 76 relatively healthy community volunteers ages 30-54. Results: Peripheral levels of IL-6 covaried inversely with hippocampal grey matter volume, and this relationship persisted after accounting for several possible confounders, including age, gender, race, years of education, percent body fat, blood pressure, smoking, physical activity, hours of sleep, alcohol use, and total grey matter volume. Conclusions: To our knowledge, this is the first report of a relationship between a peripheral marker of IL-6 and hippocampal grey matter volume, raising the possibility that low-grade systemic inflammation could plausibly presage subclinical cognitive decline in part via structural neural pathways.