{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:48:47Z","timestamp":1785235727448,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small\u2010vessel disease, measured by T2\u2010weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early\u2010stage PD affect later cognitive decline via mediation through cerebral small\u2010vessel disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>De novo PD patients (N = 365) and age\u2010matched controls (N = 174) with baseline T2\u2010weighted\/ fluid\u2010attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disease\u2013Autonomic) on future cognitive decline (measured by Montreal Cognitive Assessment) in an average of 4\u2009years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mediation analysis supported the existence of a full mediation of WMHs on the effect of diastolic orthostatic hypotension in patients with PD and future cognitive decline (average causal mediation effect: ab = \u22120.032, 95% confidence interval = \u22120.064 to \u22120.01, <jats:italic>P<\/jats:italic>\u2009=\u20090.01). There was also a partial mediation for overall autonomic dysfunction (ab = \u22120.027, 95% confidence interval = \u22120.054 to 0.00, <jats:italic>P<\/jats:italic>\u2009=\u20090.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>WMHs fully mediate the effect of diastolic orthostatic hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.13003","type":"journal-article","created":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T14:11:38Z","timestamp":1592057498000},"page":"639-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["White Matter Hyperintensities Mediate Impact of Dysautonomia on Cognition in Parkinson's Disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-2672","authenticated-orcid":false,"given":"Mahsa","family":"Dadar","sequence":"first","affiliation":[{"name":"NeuroImaging and Surgical Tools Laboratory, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-9351","authenticated-orcid":false,"given":"Seyed\u2010Mohammad","family":"Fereshtehnejad","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"Division of Neurology, Department of Medicine University of Ottawa and Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashar","family":"Zeighami","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Dagher","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B.","family":"Postuma","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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