title: Carotid atherosclerotic markers in CADASIL.
abstract: OBJECTIVE
  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL.
  
  
  METHODS
  Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded.
  
  
  RESULTS
  Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01).
  
  
  CONCLUSIONS
  The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results.
authors.affiliation: Department of Neurology, Centre de Référence pour les maladies rares des Vaisseaux du Cerveau et de l'Oeil, Groupe Hospitalier Lariboisière-Fernand Widal, APHP, Université Paris 7-Denis Diderot, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mawet
authors.forename: Katayoun
authors.initials: K
authors.lastname: Vahedi
authors.forename: Mounir
authors.initials: M
authors.lastname: Aout
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.forename: Pierre Jean
authors.initials: PJ
authors.lastname: Touboul
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D046589:CADASIL / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000523:psychology; D002340:Carotid Artery Diseases / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000523:psychology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D010297:Paris; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D018616:Ultrasonography, Doppler, Duplex; D055815:Young Adult
chemical_list: D015415:Biomarkers