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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCRAIG, Chesney E.
dc.contributor.authorJENKINSON, Ned J.
dc.contributor.authorBRITTAIN, John-Stuart
dc.contributor.authorGROTHE, Michel J.
dc.contributor.authorROCHESTER, Lynn
dc.contributor.authorSILVERDALE, Monty
dc.contributor.authorALHO, Ana T. D. L.
dc.contributor.authorALHO, Eduardo J. L.
dc.contributor.authorHOLMES, Paul S.
dc.contributor.authorRAY, Nicola J.
dc.identifier.citationMOVEMENT DISORDERS, v.35, n.7, p.1199-1207, 2020
dc.description.abstractBackground There is an urgent need to identify individuals at risk of postural instability and gait difficulties, and the resulting propensity for falls, in Parkinson's disease. Objectives Given known relationships between posture and gait and degeneration of the cholinergic pedunculopontine nucleus, we investigated whether metrics of pedunculopontine nucleus microstructural integrity hold independent utility for predicting future postural instability and gait difficulties and whether they could be combined with other candidate biomarkers to improve prognostication of these symptoms. Methods We used stereotactic mapping of the pedunculopontine nucleus and diffusion tensor imaging to extract baseline pedunculopontine nucleus diffusivity metrics in 147 participants with Parkinson's disease and 65 controls enrolled in the Parkinson's Progression Markers Initiative. We also recorded known candidate markers of posture and gait changes: loss of caudate dopamine and CSF beta-amyloid 1-42 levels at baseline; as well as longitudinal progression motor symptoms over 72-months. Results Survival analyses revealed that reduced dopamine in the caudate and increased axial diffusivity in the pedunculopontine nucleus incurred independent risk of postural instability and gait difficulties. Binary logistic regression and receiver operating characteristics analysis in 117 participants with complete follow-up data at 60 months revealed that only pedunculopontine nucleus microstructure provided more accurate discriminative ability for predicting future postural instability and gait difficulties than clinical and demographic variables alone. Conclusion Dopaminergic and cholinergic loss incur independent risk for future postural instability and gait difficulties, and pedunculopontine nucleus microstructure can be used to prognosticate these symptoms from early Parkinson's disease stages. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.eng
dc.description.sponsorshipMichael J. Fox Foundation for Parkinson's Research
dc.description.sponsorshipWellcome TrustWellcome Trust
dc.relation.ispartofMovement Disorders
dc.subjectParkinson's diseaseeng
dc.subjectPedunculopontine nucleuseng
dc.subjectPostural instability and gait difficultieseng
dc.subjectprognostic markerseng
dc.subject.otherbasal forebrain atrophyeng
dc.subject.othercognitive declineeng
dc.titlePedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Diseaseeng
dc.rights.holderCopyright WILEYeng
dc.subject.wosClinical Neurologyeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Chesney E.:Manchester Metropolitan Univ, Dept Psychol, Hlth Psychol & Communities Res Ctr, Manchester, Lancs, England, Ned J.:Univ Birmingham, Sch Sport Exercise & Rehabil Sci, Birmingham, W Midlands, England; Univ Birmingham, Ctr Human Brain Hlth, Birmingham, W Midlands, England, John-Stuart:Univ Birmingham, Behav Brain Sci Ctr, Sch Psychol, Birmingham, W Midlands, England, Michel J.:German Ctr Neurodegenerat Dis, Rostock, Germany; Univ Seville, Virgen Rocio Univ Hosp, Seville Inst Biomed, Movement Disorder Unit,Neurol & Neurophysiol Serv, Seville, Spain, Lynn:Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England, Monty:Univ Manchester, Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Dept Neurol, Manchester, Lancs, England, Paul S.:Manchester Metropolitan Univ, Dept Psychol, Hlth Psychol & Communities Res Ctr, Manchester, Lancs, England, Nicola J.:Manchester Metropolitan Univ, Dept Psychol, Hlth Psychol & Communities Res Ctr, Manchester, Lancs, England
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