Physicians' Academy for Cardiovascular Education

Midlife systemic inflammation may promote the development of white matter dysfunction

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study

Literature - Walker KA, Power MC, Hoogeveen RC, et al. - Stroke 2017;48: 3196-3202


Older adults often have cerebral small vessel disease (SVD) and white matter (WM) abnormalities, which are associated with cognitive decline and dementia [1,2]. It is not clear whether systemic inflammation contributes to the pathogenesis of these structural brain abnormalities.

In this sub-analysis of the Atherosclerosis Risk In Communities (ARIC) study, the relationships between midlife high-sensitivity (hs)CRP and late-life measures of WM hyperintensity (WMH) volume, deep and periventricular WM microstructure (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and cerebral microbleeds (CMBs) were examined in adults without dementia. Since race and APOE ε4 allele status may influence the effect of inflammatory stimuli on vascular function [3,4], the modifying effect of each of these factors was also examined.

ARIC is an ongoing community-based, prospective study, which initially enrolled 15792 adults aged 45 - 65 years, of whom 1978 participants underwent brain MRI. Subjects with poor or incomplete MRI data, or with missing hsCRP or other covariates data, as well as those with dementia, chronic inflammatory diseases, intracranial abnormalities, and race other than white or black, were excluded, leaving 1485 participants for the analysis.

Main results


In a sub-analysis of the ARIC study, midlife systemic inflammation was associated with the development of chronic microangiopathic structural WM abnormalities in the elderly. These results provide insight into the temporal relationship between systemic inflammation and brain health and support the hypothesis that systemic inflammation plays a role in the pathogenesis of late-life WM dysfunction.


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