Gait variability is linked to the atrophy of the Nucleus Basalis of Meynert and is resistant to STN DBS in Parkinson's disease.
Acetylcholine
Basal forebrain
Cholinergic
Deep brain stimulation
Dopaminergic
Gait
Gait variability
Nucleus Basalis of Meynert
Parkinson's disease
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
23
06
2020
revised:
26
09
2020
accepted:
06
10
2020
pubmed:
13
10
2020
medline:
26
10
2021
entrez:
12
10
2020
Statut:
ppublish
Résumé
Parkinson's disease (PD) is a systemic brain disorder where the cortical cholinergic network begins to degenerate early in the disease process. Readily accessible, quantitative, and specific behavioral markers of the cortical cholinergic network are lacking. Although degeneration of the dopaminergic network may be responsible for deficits in cardinal motor signs, the control of gait is a complex process and control of higher-order aspects of gait, such as gait variability, may be influenced by cognitive processes attributed to cholinergic networks. We investigated whether swing time variability, a metric of gait variability that is independent from gait speed, was a quantitative behavioral marker of cortical cholinergic network integrity in PD. Twenty-two individuals with PD and subthalamic nucleus (STN) deep brain stimulation (PD-DBS cohort) and twenty-nine age-matched controls performed a validated stepping-in-place (SIP) task to assess swing time variability off all therapy. The PD-DBS cohort underwent structural MRI scans to measure gray matter volume of the Nucleus Basalis of Meynert (NBM), the key node in the cortical cholinergic network. In order to determine the role of the dopaminergic system on swing time variability, it was measured ON and OFF STN DBS in the PD-DBS cohort, and on and off dopaminergic medication in a second PD cohort of thirty-two individuals (PD-med). A subset of eleven individuals in the PD-DBS cohort completed the SIP task again off all therapy after three years of continuous DBS to assess progression of gait impairment. Swing time variability was significantly greater (i.e., worse) in PD compared to controls and greater swing time variability was related to greater atrophy of the NBM, as was gait speed. STN DBS significantly improved cardinal motor signs and gait speed but did not improve swing time variability, which was replicated in the second cohort using dopaminergic medication. Swing time variability continued to worsen in PD, off therapy, after three years of continuous STN DBS, and NBM atrophy showed a trend for predicting the degree of increase. In contrast, cardinal motor signs did not progress. These results demonstrate that swing time variability is a reliable marker of cortical cholinergic health, and support a framework in which higher-order aspects of gait control in PD are reliant on the cortical cholinergic system, in contrast to other motor aspects of PD that rely on the dopaminergic network.
Identifiants
pubmed: 33045357
pii: S0969-9961(20)30409-5
doi: 10.1016/j.nbd.2020.105134
pmc: PMC7711311
mid: NIHMS1638376
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105134Subventions
Organisme : NINDS NIH HHS
ID : R21 NS096398
Pays : United States
Organisme : NINDS NIH HHS
ID : UH3 NS107709
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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