title: Tissue microstructural changes are independently associated with cognitive impairment in cerebral amyloid angiopathy.
abstract: OBJECTIVE
  Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment.
  
  
  METHODS
  Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0+/-22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding.
  
  
  RESULTS
  Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4x10(-4) versus 11.7x10(-4) mm(2)/s; P=0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1x10(-4) mm(2)/s increase=2.45, 95% CI 1.11 to 5.40, P=0.04).
  
  
  CONCLUSIONS
  Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage.
authors.affiliation: Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Stroke Research Center, 175 Cambridge Street, Suite 300, Boston, MA 02114, USA. aviswanathan1@partners.org
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Pratik
authors.initials: P
authors.lastname: Patel
authors.forename: Rosanna
authors.initials: R
authors.lastname: Rahman
authors.forename: R N Kaveer
authors.initials: RN
authors.lastname: Nandigam
authors.forename: Catherine
authors.initials: C
authors.lastname: Kinnecom
authors.forename: Luc
authors.initials: L
authors.lastname: Bracoud
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
mesh_terms: D000368:Aged; D001158:Arteries / Q000473:pathology; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000473:pathology; D003072:Cognition Disorders / Q000150:complications* / Q000175:diagnosis*; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011795:Surveys and Questionnaires