{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:26:21Z","timestamp":1789053981111,"version":"build-2803163510"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000769","name":"University of Oxford","doi-asserted-by":"publisher","award":["NIHR203316"],"award-info":[{"award-number":["NIHR203316"]}],"id":[{"id":"10.13039\/501100000769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012091","name":"NIHR Clinical Research Network Thames Valley and South Midlands","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012091","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203311"],"award-info":[{"award-number":["NIHR203311"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203316"],"award-info":[{"award-number":["NIHR203316"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Oxford Health Clinical Research Facility"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203139\/Z\/16\/Z"],"award-info":[{"award-number":["203139\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203139\/A\/16\/Z"],"award-info":[{"award-number":["203139\/A\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The neuropathological process in Parkinson\u2019s disease (PD) and Lewy body disorders has been shown to extend well beyond the degeneration of the dopaminergic system, affecting other neuromodulatory systems in the brain, which play crucial roles in the clinical expression and progression of these disorders.<\/jats:p>\n                  <jats:p>Here, we investigate the role of the macrostructural integrity of the nucleus basalis of Meynert (NbM), the main source of cholinergic input to the cerebral cortex, in cognitive function, clinical manifestation and disease progression in non-demented subjects with PD and individuals with isolated REM sleep behaviour disorder (iRBD).<\/jats:p>\n                  <jats:p>Using structural MRI data from 393 early PD patients, 128 iRBD patients and 186 controls from two longitudinal cohorts, we found significantly lower NbM grey matter volume in both PD (\u03b2 = \u221212.56, P = 0.003) and iRBD (\u03b2 = \u221216.41, P = 0.004) compared to controls. In PD, higher NbM volume was associated with better higher-order cognitive function (\u03b2 = 0.10, P = 0.045), decreased non-motor (\u03b2 = \u22120.66, P = 0.026) and motor (\u03b2 = \u22121.44, P = 0.023) symptom burden, and lower risk of future conversion to dementia [hazard ratio (HR) &amp;lt; 0.400, P &amp;lt; 0.004]. Higher NbM volume in iRBD was associated with decreased future risk of phenoconversion to PD or dementia with Lewy bodies (DLB) (HR &amp;lt; 0.490, P &amp;lt; 0.016). However, despite similar NbM volume deficits to those seen in PD, associations between NbM structural deficits and current disease burden or clinical state were less pronounced in iRBD.<\/jats:p>\n                  <jats:p>These findings identify NbM volume as a potential biomarker with dual utility: predicting cognitive decline and disease progression in early PD, while also serving as an early indicator of phenoconversion risk in prodromal disease. The presence of structural deficits before clear clinical correlates in iRBD suggests complex compensatory mechanisms may initially mask cholinergic dysfunction, with subsequent failure of these mechanisms potentially contributing to clinical conversion.<\/jats:p>","DOI":"10.1093\/brain\/awaf168","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T09:24:47Z","timestamp":1746177887000},"page":"226-237","source":"Crossref","is-referenced-by-count":10,"title":["Cholinergic degeneration in prodromal and early Parkinson\u2019s disease: a link to present and future disease states"],"prefix":"10.1093","volume":"149","author":[{"given":"Tamir","family":"Eisenstein","sequence":"first","affiliation":[{"name":"Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolien","family":"Groenewald","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludo","family":"van Hillegondsberg","sequence":"additional","affiliation":[{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falah","family":"Al Hajraf","sequence":"additional","affiliation":[{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University , Kuwait City ,","place":["Kuwait"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zerenner","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol BS8 2PS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3419-0354","authenticated-orcid":false,"given":"Michael A","family":"Lawton","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol BS8 2PS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6648-3007","authenticated-orcid":false,"given":"Yoav","family":"Ben-Shlomo","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol BS8 2PS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-9353","authenticated-orcid":false,"given":"Ludovica","family":"Griffanti","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford , Oxford OX3 7JX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-5841","authenticated-orcid":false,"given":"Michele T","family":"Hu","sequence":"additional","affiliation":[{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-2801","authenticated-orcid":false,"given":"Johannes C","family":"Klein","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Oxford Parkinson\u2019s Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU 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