title: Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol.
abstract: BACKGROUND
  Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated.
  
  
  METHODS
  The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI.
  
  
  CONCLUSIONS
  The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism.
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.
authors.forename: Anouk Gw
authors.initials: AG
authors.lastname: van Norden
authors.forename: Karlijn F
authors.initials: KF
authors.lastname: de Laat
authors.forename: Rob Ar
authors.initials: RA
authors.lastname: Gons
authors.forename: Inge Wm
authors.initials: IW
authors.lastname: van Uden
authors.forename: Ewoud J
authors.initials: EJ
authors.lastname: van Dijk
authors.forename: Lucas Jb
authors.initials: LJ
authors.lastname: van Oudheusden
authors.forename: Rianne Aj
authors.initials: RA
authors.lastname: Esselink
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.forename: Baziel Gm
authors.initials: BG
authors.lastname: van Engelen
authors.forename: Machiel J
authors.initials: MJ
authors.lastname: Zwarts
authors.forename: Indira
authors.initials: I
authors.lastname: Tendolkar
authors.forename: Marcel G
authors.initials: MG
authors.lastname: Olde-Rikkert
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: van der Vlugt
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
authors.forename: Frank-Erik
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D002985:Clinical Protocols; D003704:Dementia / Q000150:complications; D056324:Diffusion Tensor Imaging / Q000379:methods; D018450:Disease Progression; D005260:Female; D015577:Geriatric Assessment / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications; D011446:Prospective Studies; D012307:Risk Factors