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Cholinergic Basal Forebrain Volumes Predict Gait Decline in Parkinson's Disease

Lookup NU author(s): Joanna Wilson, Professor Alison Yarnall, Dr Brook Galna, Dr Rachael LawsonORCiD, Dr Lisa AlcockORCiD, Dr Gordon Duncan, Dr Tien Kheng Khoo, Professor John O'Brien, Professor David Burn, Professor John-Paul TaylorORCiD, Professor Lynn RochesterORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Gait disturbance is an early, disabling feature of Parkinson’s disease that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease-specific gait impairment. Objective: To evaluate associations between sub-regional cholinergic basal forebrain volumes and longitudinal progression of gait impairment in Parkinson’s disease. Methods: 99 Parkinson’s disease and 47 control participants completed gait assessments via an instrumented walkway during two minutes of continuous walking, at baseline and for up to three years, from which 16 spatiotemporal characteristics were derived. Sub-regional cholinergic basal forebrain volumes were measured at baseline via MRI and a regional map derived from post-mortem histology. Univariate analyses evaluated cross-sectional associations between sub-regional volumes and gait. Linear mixed-effects models assessed whether volumes predicted longitudinal gait changes. Results: There were no cross-sectional, age-independent relationships between sub-regional volumes and gait. However, nucleus basalis of Meynert volumes predicted longitudinal gait changes unique to Parkinson’s disease. Specifically, smaller nucleus basalis of Meynert volume predicted increasing step time variability (p=0.019) and shortening swing time (p=0.015); smaller posterior nucleus portions predicted shortening step length (p=0.007) and increasing step time variability (p=0.041). Conclusions: This is the first study to demonstrate that degeneration of the cortical cholinergic system predicts longitudinal progression of gait impairments in Parkinson’s disease. Measures of this degeneration may therefore provide a novel biomarker for identifying future mobility loss and falls.Parkinson’s disease, structural MRI, gait, NBM, acetylcholine

Publication metadata

Author(s): Wilson J, Yarnall AJ, Craig CE, Galna B, Lord S, Morris R, Lawson RA, Alcock L, Duncan GW, Khoo TK, O'Brien JT, Burn DJ, Taylor JP, Ray NJ, Rochester L

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2021

Volume: 36

Issue: 3

Pages: 611-621

Print publication date: 01/03/2021

Online publication date: 31/12/2020

Acceptance date: 16/11/2020

Date deposited: 29/01/2021

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/mds.28453


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Funder referenceFunder name
Newcastle CRF Infrastructure funding
Wellcome Trust