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. 2014 Sep 4;9(9):e106521.
doi: 10.1371/journal.pone.0106521. eCollection 2014.

Interleukin-6, age, and corpus callosum integrity

Brianne M Bettcher  1 , Christa L Watson  1 , Christine M Walsh  1 , Iryna V Lobach  1 , John Neuhaus  1 , Joshua W Miller  2 , Ralph Green  3 , Nihar Patel  1 , Shubir Dutt  1 , Edgar Busovaca  1 , Howard J Rosen  1 , Kristine Yaffe  4 , Bruce L Miller  1 , Joel H Kramer  1
Affiliations

Interleukin-6, age, and corpus callosum integrity

Brianne M Bettcher et al. PLoS One. .

Abstract

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Whole brain analysis of IL-6 levels and white matter integrity.
Whole brain TBSS analysis displayed at p≤01, using TFCE and corrected for multiple comparisons. The figure shows white matter regions inversely associated with IL-6 levels, thereby displaying areas in which higher IL-6 levels were associated with lower fractional anisotropy. Significant results were primarily restricted to the body and splenium, and extend into the genu of the corpus callosum.
Figure 2
Figure 2. Displays slopes for the association between IL-6 and white matter integrity in the genu, body, and splenium of the corpus callosum across age (solid line) accompanied by 95% confidence intervals (dashed lines).
IL-6 marginal effects are adjusted for demographic variables and vascular factors/blood markers.
Figure 3
Figure 3. Scatterplots display the association between IL-6 levels and white matter integrity, as a function of age tertiles (for descriptive purposes).
White matter fractional anisotropy variables (i.e. genu, body, splenium of the corpus callosum) were regressed over covariates to create a residualized variable. Age was divided into tertiles; ‘0’ reflects the lowest ages in our sample (<67 years), ‘1’ reflects the middle third of ages (67–71.9 years), and ‘2’ indicates the highest ages (≥72 years).
See this image and copyright information in PMC

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