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Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches

Lookup NU author(s): Professor Alison Yarnall


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© 2022 Elsevier Ltd. In patients with Parkinson's disease, heterogeneous cholinergic system changes can occur in different brain regions. These changes correlate with a range of clinical features, both motor and non-motor, that are refractory to dopaminergic therapy, and can be conceptualised within a systems-level framework in which nodal deficits can produce circuit dysfunctions. The topographies of cholinergic changes overlap with neural circuitries involved in sleep and cognitive, motor, visuo-auditory perceptual, and autonomic functions. Cholinergic deficits within cognition network hubs predict cognitive deficits better than do total brain cholinergic changes. Postural instability and gait difficulties are associated with cholinergic system changes in thalamic, caudate, limbic, neocortical, and cerebellar nodes. Cholinergic system deficits can involve also peripheral organs. Hypercholinergic activity of mesopontine cholinergic neurons in people with isolated rapid eye movement (REM) sleep behaviour disorder, as well as in the hippocampi of cognitively normal patients with Parkinson's disease, suggests early compensation during the prodromal and early stages of Parkinson's disease. Novel pharmacological and neurostimulation approaches could target the cholinergic system to treat motor and non-motor features of Parkinson's disease.

Publication metadata

Author(s): Bohnen NI, Yarnall AJ, Weil RS, Moro E, Moehle MS, Borghammer P, Bedard M-A, Albin RL

Publication type: Review

Publication status: Published

Journal: The Lancet Neurology

Year: 2022

Volume: 21

Issue: 4

Pages: 381-392

Print publication date: 01/04/2022

Online publication date: 04/02/2022

Acceptance date: 02/04/2018

ISSN (print): 1474-4422

ISSN (electronic): 1474-4465

Publisher: Elsevier Ltd


DOI: 10.1016/S1474-4422(21)00377-X

PubMed id: 35131038