{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:14:09Z","timestamp":1790954049579,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross\u2010sectionally, however, there are little longitudinal data on whether SVD increases risk of incident parkinsonism itself. We investigated the relation between baseline SVD severity as well as SVD progression, and incident parkinsonism over a follow\u2010up of 14\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 503 participants with SVD, and without parkinsonism at baseline, from the RUN DMC prospective cohort study. Baseline inclusion was performed in 2006 and follow\u2010up took place in 2011, 2015, and 2020, including magnetic resonance imaging (MRI) and motor assessments. Parkinsonism was diagnosed according to the UK Brain Bank criteria, and stratified into vascular parkinsonism (VaP) and idiopathic Parkinson's disease (IPD). Linear mixed\u2010effect models were constructed to estimate individual rate changes of MRI\u2010characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Follow\u2010up for incident parkinsonism was near\u2010complete (99%). In total, 51 (10.2%) participants developed parkinsonism (33 VaP, 17 IPD, and 1 progressive supranuclear palsy). Patients with incident VaP had higher SVD burden compared with patients with IPD. Higher baseline white matter hyperintensities (hazard ratio [HR]\u00a0=\u00a01.46 per 1\u2010SD increase, 95% confidence interval [CI]\u00a0=\u00a01.21\u20131.78), peak width of skeletonized mean diffusivity (HR\u00a0=\u00a01.66 per 1\u2010SD increase, 95% CI\u00a0=\u00a01.34\u20132.05), and presence of lacunes (HR\u00a0=\u00a01.84, 95% CI\u00a0=\u00a00.99\u20133.42) were associated with increased risk of all\u2010cause parkinsonism. Incident lacunes were associated with incident VaP (HR\u00a0=\u00a04.64, 95% CI\u00a0=\u00a01.32\u201316.32).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Both baseline SVD severity and SVD progression are independently associated with long\u2010term parkinsonism. Our findings indicate a causal role of SVD in parkinsonism. Future studies are needed to examine the underlying pathophysiology of this relation. ANN NEUROL 2023;93:1130\u20131141<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26615","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T03:31:42Z","timestamp":1675999902000},"page":"1130-1141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cerebral Small Vessel Disease Progression Increases Risk of Incident Parkinsonism"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-4109","authenticated-orcid":false,"given":"Mina A.","family":"Jacob","sequence":"first","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Neurology Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra","family":"Bergkamp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-4050","authenticated-orcid":false,"given":"Sirwan K. L.","family":"Darweesh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza M. Y.","family":"Gelissen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Marques","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroimaging Cognition and Behaviour  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Norris","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroimaging Cognition and Behaviour  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Duering","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Center (MIAC AG) and qbig, Department of Biomedical Engineering University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne A. 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