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

Abstract

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.

Figures

Figure 1

Higher levels of plasma interleukin-6 (IL-6) among 76 adults were associated with decreased grey matter volume in the left, but not right, hippocampus at a family-wise error rate (FWE) corrected level of statistical significance. For the left hippocampus, the x, y, & z MNI coordinates for the peak association between IL-6 and grey matter volume were -21, -42, -2; t(1, 71) = 3.82, pFWE = 0.045, k = 35. Left panel: Statistical parametric maps profiling clusters of the left and right hippocampus where higher IL-6 was associated decreased grey matter volume after controlling for age, sex, race, and total grey matter volume in a region-of-interest analysis. For display, maps are thresholded at puncorrected < 0.05. Right panel: Plotted along the y-axis are extracted left hippocampal grey matter volume values in standardized (z score) units adjusted for age, sex, race, and total grey matter volume. Plotted along the x-axis are transformed plasma IL-6 values (less negative values indicate higher IL-6 levels). *p < 0.01.