title: Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL.
abstract: OBJECTIVE
  Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL.
  
  
  METHODS
  Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested.
  
  
  RESULTS
  BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (P<0.0001), Mini-Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (P<0.0001), volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages.
  
  
  CONCLUSIONS
  In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.
authors: Department of Neurology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, and Université Paris VII, Paris, France.
authors: Eric
authors: E
authors: Jouvent
authors: Anand
authors: A
authors: Viswanathan
authors: Jean-François
authors: JF
authors: Mangin
authors: Mike
authors: M
authors: O'Sullivan
authors: Jean-Pierre
authors: JP
authors: Guichard
authors: Andreas
authors: A
authors: Gschwendtner
authors: Rodica
authors: R
authors: Cumurciuc
authors: Frédérique
authors: F
authors: Buffon
authors: Nils
authors: N
authors: Peters
authors: Chahin
authors: C
authors: Pachaï
authors: Marie-Germaine
authors: MG
authors: Bousser
authors: Martin
authors: M
authors: Dichgans
authors: Hugues
authors: H
authors: Chabriat
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D020520:Brain Infarction / Q000150:complications / Q000473:pathology*; D046589:CADASIL / Q000150:complications / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies