Circulating Inflammatory Markers Are Associated With Magnetic Resonance Imaging-Visible Perivascular Spaces But Not Directly With White Matter Hyperintensities

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Abstract
Background and Purpose—: White matter hyperintensities (WMH) and perivascular spaces (PVS) are features of small vessel disease, found jointly on MRI of older people. Inflammation is a prominent pathological feature of small vessel disease. We examined the association between inflammation, PVS, and WMH in the Lothian Birth Cohort 1936 (N=634). Methods—: We measured plasma fibrinogen, C-reactive protein, and interleukin-6 and rated PVS in 3 brain regions. We measured WMH volumetrically and visually using the Fazekas scale. We derived latent variables for PVS, WMH , and Inflammation from measured PVS, WMH, and inflammation markers and modelled associations using structural equation modelling. Results—: After accounting for age, sex, stroke, and vascular risk factors, PVS were significantly associated with WMH (β=0.47; P Inflammation was weakly but significantly associated with PVS (β=0.12; P =0.048), but not with WMH (β=0.02; P =NS). Conclusions—: Circulating inflammatory markers are weakly associated with MR-visible PVS, but not directly with WMH. Longitudinal studies should examine whether visible PVS predate WMH progression and whether inflammation modulators can prevent small vessel disease.

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