title: MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study.
abstract: BACKGROUND
  Cognitive decline is one of the clinical hallmarks of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebrovascular disease caused by NOTCH3 mutations. In this 7-year follow-up study, we aimed to determine whether there are associations between the different radiologic hallmarks in CADASIL and decline in specific cognitive domains.
  
  
  METHODS
  Twenty-five NOTCH3 mutation carriers and 13 controls had standardized neuropsychological testing and MRI examinations at baseline and after a follow-up of 7 years. To identify longitudinal associations between MRI abnormalities and cognitive decline, correlation analysis was used.
  
  
  RESULTS
  At follow-up, mutation carriers showed a decline in global cognitive function (CAMCOG, p < 0.01) and in the cognitive domains language, memory, and executive function, compared to controls. Cognitive decline, especially executive dysfunction, was associated with increase in lacunar infarcts, microbleeds, and ventricular volume. In contrast, WMHs and brain atrophy were not associated with cognitive decline.
  
  
  CONCLUSIONS
  Increase in lacunar infarcts, microbleeds, and ventricular volume, but not white matter lesions or atrophy, are associated with cognitive decline in the process of CADASIL in younger-aged, mildly affected patients with CADASIL.
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. m.k.liem@lumc.nl
authors.forename: M K
authors.initials: MK
authors.lastname: Liem
authors.forename: S A J
authors.initials: SA
authors.lastname: Lesnik Oberstein
authors.forename: J
authors.initials: J
authors.lastname: Haan
authors.forename: I L
authors.initials: IL
authors.lastname: van der Neut
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: M A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: H A M
authors.initials: HA
authors.lastname: Middelkoop
authors.forename: J
authors.initials: J
authors.lastname: van der Grond
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D020520:Brain Infarction / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D046589:CADASIL / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics
chemical_list: D005819:Genetic Markers; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch