Journal of Movement Disorders

Original Article

Retro-Walking and Cholinergic Network Correlates in Parkinson’s Disease: Alexis Griggs, Giulia Carli, Taylor Brown, Prabesh Kanel, Stiven Roytman, Chatkaew Pongmala, Miriam van Emde Boas, Nicolaas Ida Bohnen; J Mov Disord. 2025;18(4):337-346. Published online July 30, 2025; DOI: https://doi.org/10.14802/jmd.25109

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Objective
To investigate the cholinergic underpinnings of forward and retro-walking in patients with Parkinson’s disease (PwP) using [¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]FEOBV) positron emission tomography (PET), which binds to the vesicular acetylcholine transporter.
Methods
We retrospectively included 44 PwP who underwent [¹⁸F]FEOBV PET imaging and forward- and retro-walking gait assessments. Voxelwise correlation analyses were performed to examine associations between gait velocities and [¹⁸F]FEOBV binding, controlling for levodopa equivalent dose and disease duration. Linear regression and mediation analyses were used to investigate the contribution of postural instability and gait disorder symptoms—measured using MDS-UPDRS items and the Mini-Balance Evaluation Systems Test (MiniBESTest)—as well as cognitive performance (attention, memory, executive, language, and visuospatial domains) to the observed associations.
Results
Slower retro-walking velocity was associated with lower [¹⁸F]FEOBV uptake in a subcortical–frontal–temporal cluster, including the bilateral middle frontal cortex, anterior cingulate, insula, basal forebrain, and striatal regions. No significant associations were found for forward walking time. Linear regression analyses revealed that MiniBESTest total score, reactive postural control subscore, and attention domain score were associated with both cholinergic uptake in the identified cluster and retro-walking velocities. Mediation analyses revealed that attention and reactive postural control mediated the relationship between [¹⁸F]FEOBV binding and retro-walking performance.
Conclusion
Our findings indicate that retro-walking places greater demands on brain cholinergic synaptic integrity involving subcortical-frontal and temporal cortical regions, subserving balance—particularly reactive postural control—and attentional resources compared to forward walking. Our results suggest that retro-walking might serve as part of an intervention strategy to improve balance and cognition in PwP.

Citations

Citations to this article as recorded by

Utility of the 4-meter backward walking speed test in older adults with neurodegenerative diseases
Kubra Altunkalem Seydi, Derya Kaya, Idil Yavuz, Alev Cam Mahser, Feyza Mutlay, Fatma Sena Dost, Ahmet Turan Isik
Irish Journal of Medical Science (1971 -).2026;[Epub] CrossRef

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