{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:48:49Z","timestamp":1790804929713,"version":"4.1.0"},"reference-count":124,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":106,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Research UK Clinical Research Fellowship","award":["2018B-001"],"award-info":[{"award-number":["2018B-001"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Clinical Research Career Development Fellowship","award":["201567\/Z\/16\/Z"],"award-info":[{"award-number":["201567\/Z\/16\/Z"]}]},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Parkinson\u2019s disease is a common and debilitating neurodegenerative disorder, with over half of patients progressing to postural instability, dementia or death within 10 years of diagnosis. However, the onset and rate of progression to poor outcomes is highly variable, underpinned by heterogeneity in underlying pathological processes. Quantitative and sensitive measures predicting poor outcomes will be critical for targeted treatment, but most studies to date have been limited to a single modality or assessed patients with established cognitive impairment. Here, we used multimodal neuroimaging and plasma measures in 98 patients with Parkinson\u2019s disease and 28 age-matched controls followed up over 3 years. We examined: grey matter (cortical thickness and subcortical volume), white matter (fibre cross-section, a measure of macrostructure; and fibre density, a measure of microstructure) at whole-brain and tract level; structural and functional connectivity; and plasma levels of neurofilament light chain and phosphorylated tau 181. We evaluated relationships with subsequent poor outcomes, defined as development of mild cognitive impairment, dementia, frailty or death at any time during follow-up, in people with Parkinson\u2019s disease. We show that extensive white matter macrostructural changes are already evident at baseline assessment in people with Parkinson\u2019s disease who progress to poor outcomes (n = 31): with up to 19% reduction in fibre cross-section in multiple tracts, and a subnetwork of reduced structural connectivity strength, particularly involving connections between right frontoparietal and left frontal, right frontoparietal and left parietal and right temporo-occipital and left parietal modules. In contrast, grey matter volumes and functional connectivity were preserved in people with Parkinson\u2019s disease with poor outcomes. Neurofilament light chain, but not phosphorylated tau 181 levels were increased in people with Parkinson\u2019s disease with poor outcomes, and correlated with white matter loss. These findings suggest that imaging sensitive to white matter macrostructure and plasma neurofilament light chain may be useful early markers of poor outcomes in Parkinson\u2019s disease. As new targeted treatments for neurodegenerative disease are emerging, these measures show important potential to aid patient selection for treatment and improve stratification for clinical trials.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae130","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T19:56:25Z","timestamp":1713297385000},"source":"Crossref","is-referenced-by-count":20,"title":["Neuroimaging and plasma evidence of early white matter loss in Parkinson\u2019s disease with poor outcomes"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-072X","authenticated-orcid":false,"given":"Angeliki","family":"Zarkali","sequence":"first","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London , London WC1N 3AR , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8608-7757","authenticated-orcid":false,"given":"Naomi","family":"Hannaway","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London , London WC1N 3AR , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McColgan","sequence":"additional","affiliation":[{"name":"Huntington\u2019s Disease Centre, Institute of Neurology, University College London , London WC1B 5EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK DRI Fluid Biomarker Lab and Biomarker Factory, University College London , London WC1E 6BT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Veleva","sequence":"additional","affiliation":[{"name":"UK DRI Fluid Biomarker Lab and Biomarker Factory, University College London , London WC1E 6BT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Laban","sequence":"additional","affiliation":[{"name":"UK DRI Fluid Biomarker Lab and Biomarker Factory, University College London , London WC1E 6BT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London , London WC1N 3AR , UK"},{"name":"UK DRI Fluid Biomarker Lab and Biomarker Factory, University College London , London WC1E 6BT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-4385","authenticated-orcid":false,"given":"Andrew J","family":"Lees","sequence":"additional","affiliation":[{"name":"Reta Lila Weston Institute of Neurological Studies, University College London , London WC1N 1PJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick C","family":"Fox","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London , London WC1N 3AR , UK"},{"name":"National Hospital for Neurology and Neurosurgery, University College London Hospitals , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-6325","authenticated-orcid":false,"given":"Rimona S","family":"Weil","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London , London WC1N 3AR , UK"},{"name":"National Hospital for Neurology and Neurosurgery, University College London Hospitals , London WC1N 3BG , UK"},{"name":"Movement Disorders Centre, University College London , London WC1N 3BG , UK"},{"name":"The Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London , London WC1N 3AR , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"issue":"5","key":"2024062807274439800_fcae130-B1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1212\/01.wnl.0000247740.47667.03","article-title":"Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030","volume":"68","author":"Dorsey","year":"2007","journal-title":"Neurology"},{"issue":"11","key":"2024062807274439800_fcae130-B2","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1136\/jnnp-2013-305277","article-title":"The CamPaIGN study of Parkinson\u2019s disease: 10-year outlook in an incident population-based cohort","volume":"84","author":"Williams-Gray","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry."},{"issue":"3","key":"2024062807274439800_fcae130-B3","first-page":"351","article-title":"Determinants of medical direct costs of care among patients of a memory 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