{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:53:42Z","timestamp":1759964022238,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to investigate the distribution characteristics of enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) and their associations with disease severity across the frontotemporal lobar degeneration (FTLD) syndromes spectrum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 73 controls, 39 progressive supranuclear palsy Richardson\u2019s syndrome (PSP-RS), 31 corticobasal syndrome (CBS), 47 behavioral variant frontotemporal dementia (bvFTD), 36 non-fluent variant primary progressive aphasia (nfvPPA), and 50 semantic variant primary progressive aphasia (svPPA). All subjects had brain magnetic resonance imaging (MRI) and neuropsychological tests, including progressive supranuclear palsy rating scale (PSPRS) and FTLD modified clinical dementia rating sum of boxes (FTLD-CDR). EPVS number and grade were rated on MRI in the centrum semiovale (CSO-EPVS), basal ganglia (BG-EPVS), and brain stem (BS-EPVS). Periventricular (PWMH) and deep (DWMH) were also graded on MRI. The distribution characteristics of EPVS and WMH were compared between control and disease groups. Multivariable linear regression analysis was performed to evaluate the association of EPVS and WMH with disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control subjects, PSP-RS and CBS had more BS-EPVS; CBS, bvFTD, and nfvPPA had less CSO-EPVS; all disease groups except CBS had higher PWMH (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). BS-EPVS was associated with PSPRS in PSP-RS (\u03b2 = 2.395, 95% CI 0.888\u20133.901) and CBS (\u03b2 = 3.115, 95% CI 1.584\u20134.647). PWMH was associated with FTLD-CDR in bvFTD (\u03b2 = 1.823, 95% CI 0.752\u20132.895), nfvPPA (\u03b2 = 0.971, 95% CI 0.030\u20131.912), and svPPA (OR: 1.330, 95% CI 0.457\u20132.204).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BS-EPVS could be a promising indicator of disease severity in PSP-RS and CBS, while PWMH could reflect the severity of bvFTD, nfvPPA, and svPPA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.923193","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T10:00:00Z","timestamp":1659002400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Enlarged perivascular spaces and white matter hyperintensities in patients with frontotemporal lobar degeneration syndromes"],"prefix":"10.3389","volume":"14","author":[{"given":"Ming-Liang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Bin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao-Qiao","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng-Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the 4-Repeat Tau Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/brain\/awx003","article-title":"MRI-visible perivascular space location is associated with Alzheimer\u2019s disease independently of amyloid burden.","volume":"140","author":"Banerjee","year":"2017","journal-title":"Brain"},{"key":"B2","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1016\/S0140-6736(15)00461-4","article-title":"Frontotemporal dementia.","volume":"386","author":"Bang","year":"2015","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.conb.2021.07.006","article-title":"Cerebral small vessel disease: a glymphopathy?","volume":"72","author":"Benveniste","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1016\/j.nicl.2019.101711","article-title":"Detecting frontotemporal dementia syndromes using MRI biomarkers.","volume":"22","author":"Bruun","year":"2019","journal-title":"NeuroImage Clin."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e890","DOI":"10.1212\/WNL.0000000000011121","article-title":"Association of dilated perivascular spaces and disease severity in patients with huntington disease.","volume":"96","author":"Chan","year":"2021","journal-title":"Neurology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00869-6","article-title":"White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer\u2019s disease.","volume":"13","author":"Desmarais","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1002\/mds.28473","article-title":"Global and regional changes in perivascular space in idiopathic and familial Parkinson\u2019s disease.","volume":"36","author":"Donahue","year":"2021","journal-title":"Mov. Disord."},{"key":"B8","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1161\/STROKEAHA.109.564914","article-title":"Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease.","volume":"41","author":"Doubal","year":"2010","journal-title":"Stroke"},{"key":"B9","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.neuroimage.2018.10.026","article-title":"Enlarged perivascular spaces in brain MRI: automated quantification in four regions.","volume":"185","author":"Dubost","year":"2019","journal-title":"Neuroimage"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1212\/WNL.0000000000003305","article-title":"Progression of brain atrophy in PSP and CBS over 6 months and 1 year.","volume":"87","author":"Dutt","year":"2016","journal-title":"Neurology"},{"key":"B11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging.","volume":"149","author":"Fazekas","year":"1987","journal-title":"AJR Am. J. Roentgenol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/ana.25893","article-title":"Sensitivity-specificity of tau and amyloid \u03b2 positron emission tomography in frontotemporal lobar degeneration.","volume":"88","author":"Ghirelli","year":"2020","journal-title":"Ann. Neurol."},{"key":"B13","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1093\/brain\/awm032","article-title":"A clinical rating scale for progressive supranuclear palsy.","volume":"130","author":"Golbe","year":"2007","journal-title":"Brain"},{"key":"B14","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/S1474-4422(20)30489-0","article-title":"Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial.","volume":"20","author":"H\u00f6glinger","year":"2021","journal-title":"Lancet Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.neubiorev.2020.11.007","article-title":"White matter hyperintensities and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 36 prospective studies.","volume":"120","author":"Hu","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1743","DOI":"10.1212\/WNL.0000000000011638","article-title":"Clinical and biological correlates of white matter hyperintensities in patients with behavioral-variant frontotemporal dementia and alzheimer disease.","volume":"96","author":"Huynh","year":"2021","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2.","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.biopsych.2008.03.024","article-title":"Classification of white matter lesions on magnetic resonance imaging in elderly persons.","volume":"64","author":"Kim","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B19","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1093\/brain\/awn234","article-title":"Development of methodology for conducting clinical trials in frontotemporal lobar degeneration.","volume":"131","author":"Knopman","year":"2008","journal-title":"Brain"},{"key":"B20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrneurol.2011.43","article-title":"Corticobasal degeneration: a pathologically distinct 4R tauopathy.","volume":"7","author":"Kouri","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/ana.24647","article-title":"White matter hyperintensities are a core feature of Alzheimer\u2019s disease: evidence from the dominantly inherited Alzheimer network.","volume":"79","author":"Lee","year":"2016","journal-title":"Ann. Neurol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"e291","DOI":"10.1212\/WNL.0000000000009890","article-title":"Areas of white matter hyperintensities and motor symptoms of Parkinson disease.","volume":"95","author":"Lee","year":"2020","journal-title":"Neurology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00161","article-title":"Dilated perivascular space in the midbrain may reflect dopamine neuronal degeneration in Parkinson\u2019s disease.","volume":"12","author":"Li","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1007\/s00415-020-10209-7","article-title":"MRI-visible perivascular spaces as an imaging biomarker in Fabry disease.","volume":"268","author":"Lyndon","year":"2021","journal-title":"J. Neurol."},{"key":"B25","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1136\/jnnp.2003.030858","article-title":"Enlarged perivascular spaces are associated with cognitive function in healthy elderly men.","volume":"75","author":"Maclullich","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1093\/brain\/awaa097","article-title":"Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes.","volume":"143","author":"Murley","year":"2020","journal-title":"Brain"},{"key":"B27","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s13311-021-01101-x","article-title":"Neuroimaging in frontotemporal dementia: heterogeneity and relationships with underlying neuropathology.","volume":"18","author":"Peet","year":"2021","journal-title":"Neurotherapeutics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1159\/000375153","article-title":"Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability.","volume":"39","author":"Potter","year":"2015","journal-title":"Cerebrovasc. Dis."},{"key":"B29","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders.","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol."},{"key":"B30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1212\/WNL.58.2.198","article-title":"Patterns of brain atrophy in frontotemporal dementia and semantic dementia.","volume":"58","author":"Rosen","year":"2002","journal-title":"Neurology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.neurobiolaging.2020.12.010","article-title":"Volumetric distribution of perivascular space in relation to mild cognitive impairment.","volume":"99","author":"Sepehrband","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00155-0","article-title":"The role of brain perivascular space burden in early-stage Parkinson\u2019s disease.","volume":"7","author":"Shen","year":"2021","journal-title":"NPJ Parkinsons Dis."},{"key":"B33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jalz.2019.04.007","article-title":"Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration.","volume":"16","author":"Staffaroni","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"B34","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41582-021-00541-5","article-title":"Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies.","volume":"17","author":"Stamelou","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0470-7","article-title":"(18)F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes.","volume":"11","author":"Tsai","year":"2019","journal-title":"Alzheimers Res. Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1136\/jnnp.2005.070193","article-title":"Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population.","volume":"77","author":"van den Heuvel","year":"2006","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.neurobiolaging.2016.11.002","article-title":"White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.","volume":"50","author":"Venkat","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00878-5","article-title":"Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer\u2019s continuum.","volume":"13","author":"Vilor-Tejedor","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.neurobiolaging.2020.12.014","article-title":"Association of enlarged perivascular spaces with A\u03b2 and tau deposition in cognitively normal older population.","volume":"100","author":"Wang","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"B40","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1093\/brain\/awm104","article-title":"Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson\u2019s syndrome.","volume":"130","author":"Williams","year":"2007","journal-title":"Brain"},{"key":"B42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1109\/42.906424","article-title":"Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm.","volume":"20","author":"Zhang","year":"2001","journal-title":"IEEE Trans. Med. Imaging"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.923193\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T10:00:21Z","timestamp":1659002421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.923193\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":42,"alternative-id":["10.3389\/fnagi.2022.923193"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.923193","relation":{},"ISSN":["1663-4365"],"issn-type":[{"type":"electronic","value":"1663-4365"}],"subject":[],"published":{"date-parts":[[2022,7,28]]},"article-number":"923193"}}