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The Cholinergic Brain in Parkinson's Disease

Lookup NU author(s): Dr Jacopo Pasquini, Professor David BrooksORCiD, Professor Nicola PaveseORCiD



This is the authors' accepted manuscript of a review published in its final definitive form in 2021. For re-use rights please refer to the publishers terms and conditions.


The central cholinergic system includes the basal forebrain nuclei, mainly projecting to the cortex, the mesopontine tegmental nuclei, mainly projecting to the thalamus and subcortical structures, and other groups of projecting- and inter-neurons. This system regulates many functions of human behaviour such as cognition, locomotion and sleep. In Parkinson’s disease (PD), disruption of central cholinergic transmission has been associated with cognitive decline, gait problems, freezing of gait (FOG), falls, REM sleep behaviour disorder (RBD), neuropsychiatric manifestations and olfactory dysfunction. In Braak’s neuropathological staging of PD, basal forebrain pathology occurs simultaneously with nigrostriatal denervation, while pathology in the pontine nuclei may occur before the onset of motor symptoms. Neuropathological and more recent in-vivo neuroimaging studies have detailed the clinical implications of cholinergic dysfunction in PD. Degeneration of basal forebrain nuclei and consequential cortical cholinergic denervation is associated with and may predict the subsequent development of cognitive decline and neuropsychiatric symptoms. Gait problems, FOG and falls are associated with complex dysfunction of both pontine and basal forebrain nuclei. REM sleep behaviour disorders is associated with cholinergic denervation of the limbic archicortex, specifically hippocampus and amygdala. The available evidence suggests that cholinergic dysfunction, alongside failure of the dopaminergic and other neurotransmitters systems, contributes to the generation of a specific set of clinical manifestations. Thus, a “cholinergic phenotype” can be identified as patients presenting with cognitive decline, falls and RBD. In this review we will summarise the organization of the central cholinergic system and the clinical correlates of cholinergic dysfunction in PD.

Publication metadata

Author(s): Pasquini J, Brooks DJ, Pavese N

Publication type: Review

Publication status: Published

Journal: Movement Disorders Clinical Practice

Year: 2021

Volume: 8

Issue: 7

Pages: 1012-1026

Print publication date: 01/10/2021

Online publication date: 02/08/2021

Acceptance date: 22/07/2021

ISSN (electronic): 2330-1619


DOI: 10.1002/mdc3.13319