Gait abnormalities in Parkinson's disease are associated with extracellular free-water characteristics in the substantia nigra

  • Background:Gait impairments are common in Parkinson’s disease (PD). The pathological mechanisms are complex and not thoroughly elucidated, thus quantitative and objective parameters that closely relate to gait characteristics are critically needed to improve the diagnostic assessments and monitor disease progression. The substantia nigra is a relay structure within basal ganglia brainstem loops that is centrally involved in gait modulation. Objective:We tested the hypothesis that quantitative gait biomechanics are related to the microstructural integrity of the substantia nigra and PD-relevant gait abnormalities are independent from bradykinesia-linked speed reductions. Methods:Thirty-eight PD patients and 33 age-matched control participants walked on a treadmill at fixed speeds. Gait parameters were fed into a principal component analysis to delineate relevant features. We applied the neurite orientation dispersion and density imaging (NODDI) model on diffusion-weightedBackground:Gait impairments are common in Parkinson’s disease (PD). The pathological mechanisms are complex and not thoroughly elucidated, thus quantitative and objective parameters that closely relate to gait characteristics are critically needed to improve the diagnostic assessments and monitor disease progression. The substantia nigra is a relay structure within basal ganglia brainstem loops that is centrally involved in gait modulation. Objective:We tested the hypothesis that quantitative gait biomechanics are related to the microstructural integrity of the substantia nigra and PD-relevant gait abnormalities are independent from bradykinesia-linked speed reductions. Methods:Thirty-eight PD patients and 33 age-matched control participants walked on a treadmill at fixed speeds. Gait parameters were fed into a principal component analysis to delineate relevant features. We applied the neurite orientation dispersion and density imaging (NODDI) model on diffusion-weighted MR-images to calculate the free-water content as an advanced marker of microstructural integrity of the substantia nigra and tested its associations with gait parameters. Results:Patients showed increased duration of stance phase, load response, pre-swing, and double support time, as well as reduced duration of single support and swing time. Gait rhythmic alterations associated positively with the free-water content in the right substantia nigra in PD, indicating that patients with more severe neurodegeneration extend the duration of stance phase, load response, and pre-swing. Conclusion:The results provide evidence that gait alterations are not merely a byproduct of bradykinesia-related reduced walking speed. The data-supported association between free-water and the rhythmic component highlights the potential of substantia nigra microstructure imaging as a measure of gait-dysfunction and disease-progression.show moreshow less

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Metadaten
Author:Manuel BangeGND, Gabriel Gonzalez-Escamilla, Nadine Sandra Claudia Lang, Hao Ding, Angela Radetz, Damian Marc Herz, Wolfgang Immanuel Schöllhorn, Muthuraman MuthuramanORCiDGND, Sergiu Groppa
URN:urn:nbn:de:bvb:384-opus4-1109558
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/110955
ISSN:1877-7171OPAC
ISSN:1877-718XOPAC
Parent Title (English):Journal of Parkinson's Disease
Publisher:IOS Press
Place of publication:Amsterdam
Type:Article
Language:English
Year of first Publication:2022
Publishing Institution:Universität Augsburg
Release Date:2024/01/22
Tag:Cellular and Molecular Neuroscience; Neurology (clinical)
Volume:12
Issue:5
First Page:1575
Last Page:1590
DOI:https://doi.org/10.3233/jpd-223225
Institutes:Fakultät für Angewandte Informatik
Fakultät für Angewandte Informatik / Institut für Informatik
Fakultät für Angewandte Informatik / Institut für Informatik / Professur für Informatik in der Medizintechnik
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):Deutsches Urheberrecht