title: Subcortical hyperintensity volumetrics in Alzheimer's disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory.
abstract: BACKGROUND
  Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature.
  
  
  METHODS
  Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study.
  
  
  RESULTS
  Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD.
  
  
  CONCLUSIONS
  These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer's dementia.
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, 2075 Bayview Avenue, Room A4 21, Toronto, ON M4N 3M5, Canada ; Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, ON, Canada ; Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, 2075 Bayview Avenue, Room A4 21, Toronto, ON M4N 3M5, Canada ; Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, ON, Canada ; Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McNeely
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, 2075 Bayview Avenue, Room A4 21, Toronto, ON M4N 3M5, Canada ; Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, ON, Canada ; Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Christopher Jm
authors.initials: CJ
authors.lastname: Scott
authors.affiliation: Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada ; Rotman Research Institute, Baycrest, Toronto, ON, Canada ; Ontario Brain Institute, Toronto, ON, Canada.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Stuss
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, 2075 Bayview Avenue, Room A4 21, Toronto, ON M4N 3M5, Canada ; Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Toronto, ON, Canada ; Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada ; Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada ; Rotman Research Institute, Baycrest, Toronto, ON, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black