title: Diffusion tensor imaging and cognition in cerebral small vessel disease: the RUN DMC study.
abstract: BACKGROUND
  Cerebral small vessel disease (SVD) is very common in elderly and related to cognition, although this relation is weak. This might be because the underlying pathology of white matter lesions (WML) is diverse and cannot be properly appreciated with conventional FLAIR MRI. In addition, conventional MRI is not sensitive to early loss of microstructural integrity of the normal appearing white matter (NAWM), which might be an important factor. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity and we have used this to investigate the relation between white matter integrity, in both WML and NAWM, and cognition among elderly with cerebral SVD.
  
  
  METHODS
  The RUN DMC study is a prospective cohort study among 503 independently living, non-demented elderly with cerebral SVD aged between 50 and 85 years. All subjects underwent MRI and DTI scanning. WML were segmented manually. We measured mean diffusivity (MD) and fractional anisotropy (FA), as assessed by DTI in both WML and NAWM.
  
  
  RESULTS
  Inverse relations were found between MD in the WML and NAWM and global cognitive function (β=-.11, p<0.05; β=-.18, p<0.001), psychomotor speed (β=-.15, p<0.01; β=-.18, p<0.001), concept shifting (β=-.11, p<0.05; β=-.10, p<0.05) and attention (β=-.12, p<0.05; β=-.15, p<0.001). The relation between DTI parameters in both WML and NAWM and cognitive performance was most pronounced in subjects with severe WML.
  
  
  CONCLUSIONS
  DTI parameters in both WML and NAWM correlate with cognitive performance, independent of SVD. DTI may be a promising tool in exploring the mechanisms of cognitive decline and could function as a surrogate marker for disease progression in therapeutic trials. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. a.vannorden@neuro.umcn.nl
authors.forename: Anouk G W
authors.initials: AG
authors.lastname: van Norden
authors.forename: Karlijn F
authors.initials: KF
authors.lastname: de Laat
authors.forename: Ewoud J
authors.initials: EJ
authors.lastname: van Dijk
authors.forename: Inge W M
authors.initials: IW
authors.lastname: van Uden
authors.forename: Lucas J B
authors.initials: LJ
authors.lastname: van Oudheusden
authors.forename: Rob A R
authors.initials: RA
authors.lastname: Gons
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.forename: Frank-Erik
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis* / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000473:pathology*; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011446:Prospective Studies