Abstract
The purpose of this study was to test the hypothesis that higher levels of systemic inflammation in a community sample of non-demented subjects older than seventy years of age are associated with reduced diffusion anisotropy in brain white matter and lower cognition. Ninety-five older persons without dementia underwent detailed clinical and cognitive evaluation and magnetic resonance imaging, including diffusion tensor imaging. Systemic inflammation was assessed with a composite measure of commonly used circulating inflammatory markers (C-reactive protein and tumor necrosis factor-alpha). Tract-based spatial statistics analyses demonstrated that diffusion anisotropy in the body and isthmus of the corpus callosum was negatively correlated with the composite measure of systemic inflammation, controlling for demographic, clinical and radiologic factors. Visuospatial ability was negatively correlated with systemic inflammation, and diffusion anisotropy in the body and isthmus of the corpus callosum was shown to mediate this association. The findings of the present study suggest that higher levels of systemic inflammation may be associated with lower microstructural integrity in the corpus callosum of non-demented elderly individuals, and this may partially explain the finding of reduced higher-order visual cognition in aging.
Highlights
Aging is linked to upregulation of inflammation-associated genes in the brain [1,2,3]
Tract-Based Spatial Statistics (TBSS) analysis demonstrated significant negative correlation between fractional anisotropy (FA) values in the body and isthmus of the corpus callosum and the composite measure of systemic inflammation, controlling for age, sex, level of education, and presence of white matter hyperintense (WMH) (p,0.05 corrected for multiple comparisons) (Fig. 1)
These analyses showed significant negative correlation between FA values in the body and isthmus of the corpus callosum and the composite measure of systemic inflammation (p,0.05 corrected for multiple comparisons), in a very similar spatial pattern as the first set of TBSS analyses (Fig. 1)
Summary
Aging is linked to upregulation of inflammation-associated genes in the brain [1,2,3]. Despite the important role of inflammation in aging, the relation between systemic inflammation and brain abnormalities in non-demented elderly human subjects has not been fully explored. MRI has demonstrated macro-structural brain abnormalities linked to inflammation, prior to the onset of neurocognitive deficits and dementia. Investigations of the microstructural integrity of brain tissue by means of diffusion tensor imaging (DTI) [24,25] have demonstrated an association between systemic inflammation and reduced microstructural integrity in white matter pathways of non-demented individuals [26,27]. Further investigation is necessary into the relation between systemic inflammation and microstructural brain abnormalities in non-demented elderly subjects
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