title: Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease.
abstract: OBJECTIVE
  The blood-brain barrier (BBB) is disrupted in small vessel disease patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger disease.
  
  
  METHODS
  We selected a subset of 22 Binswanger disease subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice for several years using dynamic contrast-enhanced magnetic resonance imaging. WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were coregistered. WM was divided into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined as 2 mm on each side of the WMH border. WMP was calculated in each of the 3 specific regions. We used paired t test, ANOVA, and Fisher exact test to compare individual changes.
  
  
  RESULTS
  WMP was significantly higher in subjects than in controls (P<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52% within the WMH ring (P<0.001; ANOVA).
  
  
  CONCLUSIONS
  Increased BBB permeability in normal appearing WM and close to the WMH borders supports a relationship between BBB disruption and the development of WMHs.
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.).
authors.forename: Branko N
authors.initials: BN
authors.lastname: Huisa
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.).
authors.forename: Arvind
authors.initials: A
authors.lastname: Caprihan
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.).
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thompson
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.).
authors.forename: Jillian
authors.initials: J
authors.lastname: Prestopnik
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.).
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Qualls
authors.affiliation: From the Departments of Neurology (B.N.H., J.T., J.P., G.A.R.), Neurosciences (G.A.R.), Cell Biology and Physiology (G.A.R.), Mathematics and Statistics (G.A.R.), and Clincal Translational Science Center (C.R.Q.), University of New Mexico Health Sciences Center, Albuquerque; and MIND Research Network, Albuquerque, NM (A.C.). grosenberg@salud.unm.edu.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rosenberg
mesh_terms: D000368:Aged; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D059345:Cerebral Small Vessel Diseases / Q000473:pathology / Q000503:physiopathology; D015140:Dementia, Vascular / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010539:Permeability; D066127:White Matter / Q000473:pathology*
keywords: blood–brain barrier; leukoaraiosis; magnetic resonance imaging; permeability; white matter