{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:57:40Z","timestamp":1794074260379,"version":"4.8.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015M3A9D7067240"],"award-info":[{"award-number":["2015M3A9D7067240"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1010435"],"award-info":[{"award-number":["2020R1C1C1010435"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dilated perivascular space (dPVS) has recently been reported as a biomarker for cognitive impairment in Parkinson\u2019s disease (PD). However, comprehensive interrelationships between various clinical risk factors, dPVS, white-matter hyperintensities (WMH), cognition, and motor function in PD have not been studied yet. The purpose of this study was to test whether dPVS might mediate the effect of clinical risk factors on WMH, cognition, and motor symptoms in PD patients. A total of 154 PD patients were assessed for vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), autonomic dysfunction (orthostatic hypotension and supine hypertension [SH]), APOE <jats:italic>\u03b5<\/jats:italic>4 genotype, rapid eye movement sleep-behavior disorder, motor symptoms, and cognition status. The degree of dPVS was evaluated in the basal ganglia (BG) and white matter using a 5-point visual scale. Periventricular, deep, and total WMH severity was also assessed. Path analysis was performed to evaluate the associations of these clinical factors and imaging markers with cognitive status and motor symptoms. Hypertension and SH were significantly associated with more severe BGdPVS, which was further associated with higher total WMH, consequently leading to lower cognitive status. More severe BGdPVS was also associated with worse motor symptoms, but without mediation of total WMH. Similar associations were seen when using periventricular WMH as a variable, but not when using deep WMH as a variable. In conclusion, BGdPVS mediates the effect of hypertension and SH on cognitive impairment via total and periventricular WMH, while being directly associated with more severe motor symptoms.<\/jats:p>","DOI":"10.1038\/s41531-021-00214-6","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T10:03:10Z","timestamp":1628589790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Adverse effects of hypertension, supine hypertension, and perivascular space on cognition and motor function in PD"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-6366","authenticated-orcid":false,"given":"Na-Young","family":"Shin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yae Won","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-0228","authenticated-orcid":false,"given":"Sang-Won","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yeon","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangsean","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhee","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kook-Jin","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum-soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-7977","authenticated-orcid":false,"given":"Joong-Seok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"214_CR1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1002\/mds.26632","volume":"31","author":"C McDonald","year":"2016","unstructured":"McDonald, C., Newton, J. L. & Burn, D. J. Orthostatic hypotension and cognitive impairment in Parkinson\u2019s disease: causation or association? Mov. Disord. 31, 937\u2013946 (2016).","journal-title":"Mov. Disord."},{"key":"214_CR2","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1002\/mds.26698","volume":"31","author":"N Malek","year":"2016","unstructured":"Malek, N. et al. Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson\u2019s disease. Mov. Disord. 31, 1518\u20131526 (2016).","journal-title":"Mov. Disord."},{"key":"214_CR3","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00415-020-10189-8","volume":"268","author":"A Nicoletti","year":"2021","unstructured":"Nicoletti, A. et al. Vascular risk factors, white matter lesions and cognitive impairment in Parkinson\u2019s disease: the PACOS longitudinal study. J. Neurol. 268, 549\u2013558 (2021).","journal-title":"J. Neurol."},{"key":"214_CR4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1212\/WNL.0000000000003452","volume":"88","author":"J Centi","year":"2017","unstructured":"Centi, J. et al. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology 88, 17\u201324 (2017).","journal-title":"Neurology"},{"key":"214_CR5","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.jns.2016.07.057","volume":"368","author":"SH Kang","year":"2016","unstructured":"Kang, S. H., Lee, H. M., Seo, W. K., Kim, J. H. & Koh, S. B. The combined effect of REM sleep behavior disorder and hyposmia on cognition and motor phenotype in Parkinson\u2019s disease. J. Neurol. Sci. 368, 374\u2013378 (2016).","journal-title":"J. Neurol. Sci."},{"key":"214_CR6","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1212\/WNL.45.4.672","volume":"45","author":"AI Troster","year":"1995","unstructured":"Troster, A. I. et al. The influence of depression on cognition in Parkinson\u2019s disease: a pattern of impairment distinguishable from Alzheimer\u2019s disease. Neurology 45, 672\u2013676 (1995).","journal-title":"Neurology"},{"key":"214_CR7","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.parkreldis.2016.09.011","volume":"32","author":"V Kotagal","year":"2016","unstructured":"Kotagal, V., Lineback, C., Bohnen, N. I., Albin, R. L. & Investigators, C.-P. P. S. G. Orthostatic hypotension predicts motor decline in early Parkinson disease. Parkinsonism Relat. Disord. 32, 127\u2013129 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"214_CR8","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1001\/jamaneurol.2014.1455","volume":"71","author":"IF Mata","year":"2014","unstructured":"Mata, I. F. et al. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol. 71, 1405\u20131412 (2014).","journal-title":"JAMA Neurol."},{"key":"214_CR9","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1007\/s00415-018-9077-3","volume":"266","author":"X Chen","year":"2019","unstructured":"Chen, X. et al. Cerebral small vessel disease: neuroimaging markers and clinical implication. J. Neurol. 266, 2347\u20132362 (2019).","journal-title":"J. Neurol."},{"key":"214_CR10","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1001\/jamaneurol.2017.1397","volume":"74","author":"J Ding","year":"2017","unstructured":"Ding, J. et al. Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia: the age, gene\/environment susceptibility-Reykjavik study. JAMA Neurol. 74, 1105\u20131112 (2017).","journal-title":"JAMA Neurol."},{"key":"214_CR11","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1212\/WNL.0b013e31826c1acd","volume":"79","author":"JS Kim","year":"2012","unstructured":"Kim, J. S. et al. Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease. Neurology 79, 1323\u20131331 (2012).","journal-title":"Neurology"},{"key":"214_CR12","doi-asserted-by":"publisher","first-page":"23","DOI":"10.14802\/jmd.13006","volume":"6","author":"YS Oh","year":"2013","unstructured":"Oh, Y. S., Kim, J. S. & Lee, K. S. Orthostatic and supine blood pressures are associated with white matter hyperintensities in Parkinson disease. J. Mov. Disord. 6, 23\u201327 (2013).","journal-title":"J. Mov. Disord."},{"key":"214_CR13","first-page":"853","volume":"38","author":"C Berezuk","year":"2015","unstructured":"Berezuk, C. et al. Virchow-Robin spaces: correlations with polysomnography-derived sleep parameters. Sleep 38, 853\u2013858 (2015).","journal-title":"Sleep"},{"key":"214_CR14","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1161\/01.STR.0000125859.71051.83","volume":"35","author":"F-E de Leeuw","year":"2004","unstructured":"de Leeuw, F.-E. et al. Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke 35, 1057\u20131060 (2004).","journal-title":"Stroke"},{"key":"214_CR15","doi-asserted-by":"publisher","first-page":"44477","DOI":"10.18632\/oncotarget.17724","volume":"8","author":"X Luo","year":"2017","unstructured":"Luo, X. et al. Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study. Oncotarget 8, 44477 (2017).","journal-title":"Oncotarget"},{"key":"214_CR16","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1002\/mds.27798","volume":"34","author":"YW Park","year":"2019","unstructured":"Park, Y. W. et al. Magnetic resonance imaging\u2013visible perivascular spaces in basal ganglia predict cognitive decline in Parkinson\u2019s disease. Mov. Disord. 34, 1672\u20131679 (2019).","journal-title":"Mov. Disord."},{"key":"214_CR17","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.radcr.2018.05.011","volume":"13","author":"R Conforti","year":"2018","unstructured":"Conforti, R. et al. Dilated Virchow-Robin space and Parkinson\u2019s disease: a case report of combined MRI and diffusion tensor imaging. Radiol. Case Rep. 13, 871\u2013877 (2018).","journal-title":"Radiol. Case Rep."},{"key":"214_CR18","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1212\/01.wnl.0000261483.49248.b8","volume":"68","author":"AP Duker","year":"2007","unstructured":"Duker, A. P. & Espay, A. J. Parkinsonism associated with striatal perivascular space dilation. Neurology 68, 1540\u20131540 (2007).","journal-title":"Neurology"},{"key":"214_CR19","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1192\/bjp.bp.110.090423","volume":"199","author":"SJ Colloby","year":"2011","unstructured":"Colloby, S. J. et al. Relationship of orthostatic blood pressure to white matter hyperintensities and subcortical volumes in late-life depression. Br. J. Psychiatry 199, 404\u2013410 (2011).","journal-title":"Br. J. Psychiatry"},{"key":"214_CR20","doi-asserted-by":"publisher","first-page":"e52196","DOI":"10.1371\/journal.pone.0052196","volume":"7","author":"H Soennesyn","year":"2012","unstructured":"Soennesyn, H. et al. Relationship between orthostatic hypotension and white matter hyperintensity load in older patients with mild dementia. PLoS ONE 7, e52196 (2012).","journal-title":"PLoS ONE"},{"key":"214_CR21","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1007\/s00415-009-5176-5","volume":"256","author":"TS Lim","year":"2009","unstructured":"Lim, T. S., Lee, P. H., Kim, H. S. & Yong, S. W. White matter hyperintensities in patients with multiple system atrophy. J. Neurol. 256, 1663\u20131670 (2009).","journal-title":"J. Neurol."},{"key":"214_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00685305","volume":"12","author":"CM Fisher","year":"1968","unstructured":"Fisher, C. M. The arterial lesions underlying lacunes. Acta Neuropathol. 12, 1\u201315 (1968).","journal-title":"Acta Neuropathol."},{"key":"214_CR23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.parkreldis.2020.04.011","volume":"75","author":"JA Palma","year":"2020","unstructured":"Palma, J. A. et al. The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension. Parkinsonism Relat. Disord. 75, 97\u2013104 (2020).","journal-title":"Parkinsonism Relat. Disord."},{"key":"214_CR24","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1007\/s00415-008-0874-y","volume":"255","author":"EC van Straaten","year":"2008","unstructured":"van Straaten, E. C. et al. Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia. J. Neurol. 255, 1302\u20131308 (2008).","journal-title":"J. Neurol."},{"key":"214_CR25","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1097\/WAD.0b013e3181d71a13","volume":"24","author":"SJ Lee","year":"2010","unstructured":"Lee, S. J. et al. Influence of white matter hyperintensities on the cognition of patients with Parkinson disease. Alzheimer Dis. Assoc. Disord. 24, 227\u2013233 (2010).","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"214_CR26","first-page":"276","volume":"40","author":"M Derejko","year":"2006","unstructured":"Derejko, M., Slawek, J., Wieczorek, D., Dubaniewicz, M. & Lass, P. [The influence of vascular risk factors and white matter hyperintensities on the degree of motor impairment in Parkinson\u2019s disease]. Neurol. Neurochir. Pol. 40, 276\u2013283 (2006).","journal-title":"Neurol. Neurochir. Pol."},{"key":"214_CR27","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1093\/brain\/awr139","volume":"134","author":"NI Bohnen","year":"2011","unstructured":"Bohnen, N. I. et al. Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson\u2019s disease. Brain 134, 2358\u20132365 (2011).","journal-title":"Brain"},{"key":"214_CR28","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1002\/mds.870100609","volume":"10","author":"G F\u00e9nelon","year":"1995","unstructured":"F\u00e9nelon, G., Gray, F., Wallays, C., Poirier, J. & Guillard, A. Parkinsonism and dilatation of the perivascular spaces (\u00e9tat cribl\u00e9) of the striatum: a clinical, magnetic resonance imaging, and pathological study. Mov. Disord. 10, 754\u2013760 (1995).","journal-title":"Mov. Disord."},{"key":"214_CR29","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1093\/brain\/121.12.2249","volume":"121","author":"NR Selden","year":"1998","unstructured":"Selden, N. R., Gitelman, D. R., Salamon-Murayama, N., Parrish, T. B. & Mesulam, M. M. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 121, 2249\u20132257 (1998). Pt 12.","journal-title":"Brain"},{"key":"214_CR30","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1146\/annurev.ne.11.030188.001033","volume":"11","author":"PS Goldman-Rakic","year":"1988","unstructured":"Goldman-Rakic, P. S. Topography of cognition: parallel distributed networks in primate association cortex. Annu Rev. Neurosci. 11, 137\u2013156 (1988).","journal-title":"Annu Rev. Neurosci."},{"key":"214_CR31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jns.2004.09.002","volume":"226","author":"DW Desmond","year":"2004","unstructured":"Desmond, D. W. The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit? J. Neurol. Sci. 226, 3\u20137 (2004).","journal-title":"J. Neurol. Sci."},{"key":"214_CR32","doi-asserted-by":"publisher","first-page":"e894","DOI":"10.1212\/WNL.0000000000006134","volume":"91","author":"G Pagano","year":"2018","unstructured":"Pagano, G. et al. REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease. Neurology 91, e894\u2013e905 (2018).","journal-title":"Neurology"},{"key":"214_CR33","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1001\/jamaneurol.2015.0703","volume":"72","author":"SM Fereshtehnejad","year":"2015","unstructured":"Fereshtehnejad, S. M. et al. New clinical subtypes of parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol. 72, 863\u2013873 (2015).","journal-title":"JAMA Neurol."},{"key":"214_CR34","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.5665\/sleep.5040","volume":"38","author":"I Arnulf","year":"2015","unstructured":"Arnulf, I. et al. Sleepiness in idiopathic REM sleep behavior disorder and Parkinson disease. Sleep 38, 1529\u20131535 (2015).","journal-title":"Sleep"},{"key":"214_CR35","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","volume":"342","author":"L Xie","year":"2013","unstructured":"Xie, L. et al. Sleep drives metabolite clearance from the adult brain. Science 342, 373\u2013377 (2013).","journal-title":"Science"},{"key":"214_CR36","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s00415-009-0119-8","volume":"256","author":"CH Williams-Gray","year":"2009","unstructured":"Williams-Gray, C. H. et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson\u2019s disease. J. Neurol. 256, 493\u2013498 (2009).","journal-title":"J. Neurol."},{"key":"214_CR37","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/BF03402043","volume":"9","author":"AE Roher","year":"2003","unstructured":"Roher, A. E. et al. Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer\u2019s disease. Mol. Med 9, 112\u2013122 (2003).","journal-title":"Mol. Med"},{"key":"214_CR38","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1161\/STROKEAHA.110.591586","volume":"41","author":"YC Zhu","year":"2010","unstructured":"Zhu, Y. C. et al. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke 41, 2483\u20132490 (2010).","journal-title":"Stroke"},{"key":"214_CR39","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3200\/JOER.98.1.5-13","volume":"98","author":"FK Stage","year":"2004","unstructured":"Stage, F. K., Carter, H. C. & Nora, A. Path analysis: an introduction and analysis of a decade of research. J. Educ. Res. 98, 5\u201313 (2004).","journal-title":"J. Educ. Res."},{"key":"214_CR40","doi-asserted-by":"publisher","first-page":"116978","DOI":"10.1016\/j.neuroimage.2020.116978","volume":"218","author":"X Zong","year":"2020","unstructured":"Zong, X. et al. Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: dependences on age, brain region, and breathing gas. Neuroimage 218, 116978 (2020).","journal-title":"Neuroimage"},{"key":"214_CR41","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1002\/mds.24893","volume":"27","author":"I Litvan","year":"2012","unstructured":"Litvan, I. et al. Diagnostic criteria for mild cognitive impairment in Parkinson\u2019s disease: movement disorder society task force guidelines. Mov. Disord. 27, 349\u2013356 (2012).","journal-title":"Mov. Disord."},{"key":"214_CR42","unstructured":"Kang, Y. & Na, D. Seoul Neuropsychological Screening Battery (Human Brain Research & Consulting Co. Incheon, 2003)."},{"key":"214_CR43","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1002\/mds.21507","volume":"22","author":"M Emre","year":"2007","unstructured":"Emre, M. et al. Clinical diagnostic criteria for dementia associated with Parkinson\u2019s disease. Mov. Disord. 22, 1689\u20131707 (2007).","journal-title":"Mov. Disord."},{"key":"214_CR44","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1002\/mds.21333","volume":"22","author":"A Schrag","year":"2007","unstructured":"Schrag, A. et al. Depression rating scales in Parkinson\u2019s disease: critique and recommendations. Mov. Disord. 22, 1077\u20131092 (2007).","journal-title":"Mov. Disord."},{"key":"214_CR45","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.parkreldis.2016.03.006","volume":"27","author":"LM Chahine","year":"2016","unstructured":"Chahine, L. M. et al. Longitudinal changes in cognition in early Parkinson\u2019s disease patients with REM sleep behavior disorder. Parkinsonism Relat. Disord. 27, 102\u2013106 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"214_CR46","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1002\/mds.23257","volume":"25","author":"J Montplaisir","year":"2010","unstructured":"Montplaisir, J. et al. Polysomnographic diagnosis of idiopathic REM sleep behavior disorder. Mov. Disord. 25, 2044\u20132051 (2010).","journal-title":"Mov. Disord."},{"key":"214_CR47","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1007\/s00415-016-8375-x","volume":"264","author":"CH Gibbons","year":"2017","unstructured":"Gibbons, C. H. et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J. Neurol. 264, 1567\u20131582 (2017).","journal-title":"J. Neurol."},{"key":"214_CR48","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s10286-011-0119-5","volume":"21","author":"R Freeman","year":"2011","unstructured":"Freeman, R. et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin. Auton. Res. 21, 69\u201372 (2011).","journal-title":"Clin. Auton. Res."},{"key":"214_CR49","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","volume":"12","author":"J Wardlaw","year":"2013","unstructured":"Wardlaw, J. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12, 822\u2013838 (2013).","journal-title":"Lancet Neurol."},{"key":"214_CR50","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/brain\/awx003","volume":"140","author":"G Banerjee","year":"2017","unstructured":"Banerjee, G. et al. MRI-visible perivascular space location is associated with Alzheimer\u2019s disease independently of amyloid burden. Brain 140, 1107\u20131116 (2017).","journal-title":"Brain"},{"key":"214_CR51","doi-asserted-by":"crossref","unstructured":"Park, M. et al. Myelin loss in white matter hyperintensities and normal-appearing white matter of cognitively impaired patients: a quantitative synthetic magnetic resonance imaging study. Eur. Radiol. 29, 4914\u20134921 (2019).","DOI":"10.1007\/s00330-018-5836-x"}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00214-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00214-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00214-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T21:55:17Z","timestamp":1670018117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00214-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,10]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["214"],"URL":"https:\/\/doi.org\/10.1038\/s41531-021-00214-6","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,10]]},"assertion":[{"value":"11 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"69"}}