64. Systemic inflammation and the integrity of brain white matter tracts

Abstract

Normal aging is associated with changes in brain structure and function that result in declines in cognitive performance and culminate in debilitating functional impairment for many. Converging evidence suggests that systemic inflammation plays a role in age-related changes in cognitive function, being associated with activation of central inflammatory mechanisms that result in neurodegeneration and associated cognitive declines. We have shown an inverse association of plasma interleukin (IL)-6, a relatively stable marker of systemic inflammation, with working memory and executive function, and with grey matter volume in the hippocampus and medial prefrontal cortex among cognitively-normal middle-aged adults. In the current study, we extend this work to an examination of the association of plasma IL-6 and C-reactive protein (CRP) with microstructural white matter tissue integrity, as assessed by diffusion tensor imaging among a sample of 155 cognitively normal mid-life adults (aged 30–50 years, 78 men). Results show significant inverse associations of white matter tract integrity, as assessed by whole-brain average of fractional anisotropy, with IL-6 ( r = −.22, p = .01) and CRP ( r = −.25, p = .003). These associations were largely independent of age, sex, years of education, smoking, and body mass index. Taken together, our findings provide human support for a neurobiological pathway by which inflammation could impact the brain systems implicated in memory and executive function.