Abstract TMP27: Association Of The Serum Inflammatory Markers With The Periventricular And Deep White Matter Hyperintensity

Abstract

Introduction: Markers of systemic and vascular inflammation have been associated with cerebral small vessel disease (cSVD). However, their association with cSVD lesions within individual white matter regions remains unclear. We hypothesized that there are different associations of serum cytokines with the periventricular white matter hyperintensity (PVWMH) and deep WMH (DWMH). Methods: Apparently healthy participants aged ≥50 years with brain MRI in the Genetic Study of Atherosclerosis Risk were studied. Circulating inflammatory markers measured included: hs-CRP, IL-6, MCP1, ICAM, TNF-α, VCAM and IL-4. The relative association of these markers with PVWMH and DWMH within individuals were determined using multilevel linear models adjusted for age and cardiovascular risk factors. Results: A total of 435 subjects (age 58.9±6.1 years, 58.4% female, 39.5% black) with moderate WMH burden were studied (Total WMH: 1703[607-4626] mm 3 , PVWMH :871[152-2593] mm 3 , DWMH: 388[157-1023] mm 3 ). Significant negative associations of total WMH volumes and hs-CRP (β=-0.2, P=0.04) as well as IL-6 (β=-0.15, p=0.04) were observed. The associations of total WMH with MCP-1, ICAM, VCAM, IL-4 and TNF-α were not significant. In the multilevel models, designed to compare difference between DWMH and PVWMH within individuals, there were significant differences in the relative association of PVWMH vs DWMH with hs-CRP and IL-6 (p=0.001 & p=0.04, respectively). DWMH was more strongly associated with hs-CRP and IL-6 (β=0.08, β=0.14, respectively) than PVWMH, which had negative association with these markers (β=-0.35, β=-0.05, respectively). There were no differences in the association of PVWMH vs DWMH and the other markers. Conclusions: DWMH is positively associated with increasing IL-6 and CRP when compared to PVWMH which is negatively associated with them. This suggests that systemic inflammation is more preferentially associated with DWMH lesions.