Cerebral small vessel disease and incident parkinsonism: The RUN DMC study

Helena M. Van Der Holst, Inge W.M. van Uden, Anil M. Tuladhar, Karlijn F. de Laat, Anouk G.W. van Norden, David G. Norris, Ewoud J. Van Dijk, Rianne A.J. Esselink, Bram Platel, Frank-Erik de Leeuw

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Abstract

Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011-2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95% confidence interval [CI] 1.3-2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1-1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95% CI 1.9-16.8) and a low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2-0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism.

Original languageEnglish
Pages (from-to)1569-1577
Number of pages9
JournalNeurology
Volume85
Issue number18
DOIs
Publication statusPublished - 3 Nov 2015

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Cerebral Small Vessel Diseases
Parkinsonian Disorders
Cohort Studies
Magnetic Resonance Spectroscopy
Blood Vessels
Confidence Intervals
Diffusion Tensor Imaging
Spatial Analysis

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Van Der Holst, H. M., van Uden, I. W. M., Tuladhar, A. M., de Laat, K. F., van Norden, A. G. W., Norris, D. G., ... de Leeuw, F-E. (2015). Cerebral small vessel disease and incident parkinsonism: The RUN DMC study. Neurology, 85(18), 1569-1577. https://doi.org/10.1212/WNL.0000000000002082
Van Der Holst, Helena M. ; van Uden, Inge W.M. ; Tuladhar, Anil M. ; de Laat, Karlijn F. ; van Norden, Anouk G.W. ; Norris, David G. ; Van Dijk, Ewoud J. ; Esselink, Rianne A.J. ; Platel, Bram ; de Leeuw, Frank-Erik. / Cerebral small vessel disease and incident parkinsonism : The RUN DMC study. In: Neurology. 2015 ; Vol. 85, No. 18. pp. 1569-1577.
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abstract = "Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011-2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95{\%} confidence interval [CI] 1.3-2.4) and a high number of lacunes (HR 1.4 per number increase, 95{\%} CI 1.1-1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95{\%} CI 1.9-16.8) and a low gray matter volume (HR 0.4 per SD increase, 95{\%} CI 0.2-0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism.",
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Van Der Holst, HM, van Uden, IWM, Tuladhar, AM, de Laat, KF, van Norden, AGW, Norris, DG, Van Dijk, EJ, Esselink, RAJ, Platel, B & de Leeuw, F-E 2015, 'Cerebral small vessel disease and incident parkinsonism: The RUN DMC study' Neurology, vol. 85, no. 18, pp. 1569-1577. https://doi.org/10.1212/WNL.0000000000002082

Cerebral small vessel disease and incident parkinsonism : The RUN DMC study. / Van Der Holst, Helena M.; van Uden, Inge W.M.; Tuladhar, Anil M.; de Laat, Karlijn F.; van Norden, Anouk G.W.; Norris, David G.; Van Dijk, Ewoud J.; Esselink, Rianne A.J.; Platel, Bram; de Leeuw, Frank-Erik.

In: Neurology, Vol. 85, No. 18, 03.11.2015, p. 1569-1577.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Cerebral small vessel disease and incident parkinsonism

T2 - The RUN DMC study

AU - Van Der Holst, Helena M.

AU - van Uden, Inge W.M.

AU - Tuladhar, Anil M.

AU - de Laat, Karlijn F.

AU - van Norden, Anouk G.W.

AU - Norris, David G.

AU - Van Dijk, Ewoud J.

AU - Esselink, Rianne A.J.

AU - Platel, Bram

AU - de Leeuw, Frank-Erik

PY - 2015/11/3

Y1 - 2015/11/3

N2 - Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011-2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95% confidence interval [CI] 1.3-2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1-1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95% CI 1.9-16.8) and a low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2-0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism.

AB - Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011-2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95% confidence interval [CI] 1.3-2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1-1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95% CI 1.9-16.8) and a low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2-0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism.

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Van Der Holst HM, van Uden IWM, Tuladhar AM, de Laat KF, van Norden AGW, Norris DG et al. Cerebral small vessel disease and incident parkinsonism: The RUN DMC study. Neurology. 2015 Nov 3;85(18):1569-1577. https://doi.org/10.1212/WNL.0000000000002082