Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol

Anouk Gw van Norden, Karlijn F de Laat, Rob Ar Gons, Inge Wm van Uden, Ewoud J van Dijk, Lucas Jb van Oudheusden, Rianne Aj Esselink, Bastiaan R Bloem, Baziel Gm van Engelen, Machiel J Zwarts, Indira Tendolkar, Marcel G Olde-Rikkert, Maureen J van der Vlugt, Marcel P Zwiers, David G Norris, Frank-Erik de Leeuw

Research output: Contribution to journalArticleAcademicpeer-review

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/DESIGN: 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.

DISCUSSION: 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.

Original languageEnglish
Pages (from-to)29
JournalBMC Neurology
Volume11
DOIs
Publication statusPublished - 28 Feb 2011

Cite this

van Norden, Anouk Gw ; de Laat, Karlijn F ; Gons, Rob Ar ; van Uden, Inge Wm ; van Dijk, Ewoud J ; van Oudheusden, Lucas Jb ; Esselink, Rianne Aj ; Bloem, Bastiaan R ; van Engelen, Baziel Gm ; Zwarts, Machiel J ; Tendolkar, Indira ; Olde-Rikkert, Marcel G ; van der Vlugt, Maureen J ; Zwiers, Marcel P ; Norris, David G ; de Leeuw, Frank-Erik. / Causes and consequences of cerebral small vessel disease. The RUN DMC study : a prospective cohort study. Study rationale and protocol. In: BMC Neurology. 2011 ; Vol. 11. pp. 29.
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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/DESIGN: 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.DISCUSSION: 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.",
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van Norden, AG, de Laat, KF, Gons, RA, van Uden, IW, van Dijk, EJ, van Oudheusden, LJ, Esselink, RA, Bloem, BR, van Engelen, BG, Zwarts, MJ, Tendolkar, I, Olde-Rikkert, MG, van der Vlugt, MJ, Zwiers, MP, Norris, DG & de Leeuw, F-E 2011, 'Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol' BMC Neurology, vol. 11, pp. 29. https://doi.org/10.1186/1471-2377-11-29

Causes and consequences of cerebral small vessel disease. The RUN DMC study : a prospective cohort study. Study rationale and protocol. / van Norden, Anouk Gw; de Laat, Karlijn F; Gons, Rob Ar; van Uden, Inge Wm; van Dijk, Ewoud J; van Oudheusden, Lucas Jb; Esselink, Rianne Aj; Bloem, Bastiaan R; van Engelen, Baziel Gm; Zwarts, Machiel J; Tendolkar, Indira; Olde-Rikkert, Marcel G; van der Vlugt, Maureen J; Zwiers, Marcel P; Norris, David G; de Leeuw, Frank-Erik.

In: BMC Neurology, Vol. 11, 28.02.2011, p. 29.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Causes and consequences of cerebral small vessel disease. The RUN DMC study

T2 - a prospective cohort study. Study rationale and protocol

AU - van Norden, Anouk Gw

AU - de Laat, Karlijn F

AU - Gons, Rob Ar

AU - van Uden, Inge Wm

AU - van Dijk, Ewoud J

AU - van Oudheusden, Lucas Jb

AU - Esselink, Rianne Aj

AU - Bloem, Bastiaan R

AU - van Engelen, Baziel Gm

AU - Zwarts, Machiel J

AU - Tendolkar, Indira

AU - Olde-Rikkert, Marcel G

AU - van der Vlugt, Maureen J

AU - Zwiers, Marcel P

AU - Norris, David G

AU - de Leeuw, Frank-Erik

PY - 2011/2/28

Y1 - 2011/2/28

N2 - 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/DESIGN: 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.DISCUSSION: 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.

AB - 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/DESIGN: 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.DISCUSSION: 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.

KW - Aged

KW - Aged, 80 and over

KW - Brain/blood supply

KW - Cerebrovascular Disorders/complications

KW - Clinical Protocols

KW - Dementia/complications

KW - Diffusion Tensor Imaging/methods

KW - Disease Progression

KW - Female

KW - Geriatric Assessment/methods

KW - Humans

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Middle Aged

KW - Nerve Fibers, Myelinated/pathology

KW - Parkinsonian Disorders/complications

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1186/1471-2377-11-29

DO - 10.1186/1471-2377-11-29

M3 - Article

VL - 11

SP - 29

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

ER -