title: Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities.
abstract: OBJECTIVE
  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<0.0001); 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.
authors.affiliation: From Brain Research Imaging Centre (B.S.A., S.W., Z.M., M.C.V.-H., N.A.R., S.M.M., M.E.B., J.M.W.), Centre for Cognitive Ageing and Cognitive Epidemiology (B.S.A., M.C.V.-H., N.A.R., S.M.M., A.J.G., M.E.B., J.S., I.J.D., J.M.W.), Department of Psychology (J.C., I.J.D.), and Geriatric Medicine Unit (J.S.), University of Edinburgh, Edinburgh, United Kingdom; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE), Edinburgh, United Kingdom (B.S.A., M.C.V.-H., N.A.R., S.M.M., M.E.B., J.M.W.); Department of Computer Science, Lagos State University, Nigeria (B.S.A.); and Department of Psychology, Heriot-Watt University, United Kingdom (A.J.G.).
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Aribisala
authors.forename: Stewart
authors.initials: S
authors.lastname: Wiseman
authors.forename: Zoe
authors.initials: Z
authors.lastname: Morris
authors.forename: Maria C
authors.initials: MC
authors.lastname: Valdés-Hernández
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Royle
authors.forename: Susana M
authors.initials: SM
authors.lastname: Maniega
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Janie
authors.initials: J
authors.lastname: Corley
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.forename: John
authors.initials: J
authors.lastname: Starr
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
mesh_terms: D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000473:pathology*; D002097:C-Reactive Protein / Q000032:analysis; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein
keywords: aging; inflammation; leukoaraiosis; leukoencephalopathies; magnetic resonance imaging