title: Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities.
abstract: OBJECTIVE
  To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts.
  
  
  METHODS
  We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH.
  
  
  RESULTS
  In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used.
  
  
  CONCLUSIONS
  The small effect of VRFs and LAD on WMH suggests that WMH have a large "nonvascular," nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.
authors.affiliation: From the Centre for Clinical Brain Sciences (J.M.W., F.N.D., M.V.H., Z.M., M.B., M.S.D.) and Centre for Cognitive Ageing and Cognitive Epidemiology (M.A., M.V.H., A.J.G., M.B., J.M.S., I.J.D.), University of Edinburgh, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: Michael
authors.initials: M
authors.lastname: Allerhand
authors.forename: Fergus N
authors.initials: FN
authors.lastname: Doubal
authors.forename: Maria
authors.initials: M
authors.lastname: Valdes Hernandez
authors.forename: Zoe
authors.initials: Z
authors.lastname: Morris
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Mark
authors.initials: M
authors.lastname: Bastin
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Martin S
authors.initials: MS
authors.lastname: Dennis
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D012307:Risk Factors; D014652:Vascular Diseases / Q000473:pathology