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

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 (=0.47; P<0.0001); Inflammation was weakly but significantly associated with PVS (=0.12; P=0.048), but not with WMH (=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.