title: Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report.
abstract: BACKGROUND
  White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear.
  
  
  METHODS
  Inflammatory markers were assayed in 54 elderly participants (n= 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging.
  
  
  RESULTS
  Mean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)-1β, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = -0.703,P= .002) but not in healthy elderly (ρ = 0.217,P= .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425,P= .008) but not in patients with AD (ρ = 0.174,P= .520).
  
  
  CONCLUSIONS
  Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada; University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: Departamento Psiquiatria, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cogo-Moreira
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: Szilagyi
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Holmes
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Christopher J M
authors.initials: CJ
authors.lastname: Scott
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Anxiety and Mood Disorders Department, Centre for Addictions and Mental Health, Toronto, Ontario, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Chan
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Jialun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Parco
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Medicine (Neurology Division), McMaster University, Hamilton, Ontario, Canada.
authors.forename: Demetrios J
authors.initials: DJ
authors.lastname: Sahlas
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Anxiety and Mood Disorders Department, Centre for Addictions and Mental Health, Toronto, Ontario, Canada.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Department of Medicine (Neurology Division), University of Northern British Columbia, British Columbia, Canada.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pettersen
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine (Neurology Division), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
keywords: Alzheimer's disease; Cerebrovascular disease; Confirmatory factor analysis; Cytokine; Diffusion tensor imaging; Inflammation; Microstructure; Small vessel disease; White matter disease