Cholinergic Dysfunction in Parkinson’s Disease
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There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson’s disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD.
Keywordsα-Synuclein Acetylcholine Acetylcholinesterase Basal forebrain Brainstem Cognition Dementia with Lewy bodies Dopamine Falls Gait Lewy bodies Mood Nucleus basalis of Meynert Olfaction Parkinson’s disease Pedunculopontine nucleus Pontine tegmentum Positron emission tomography (PET) Posture Progressive supranuclear palsy REM sleep behavior disorder Single photon emission computed tomography (SPECT) Striatum Thalamus Cholinergic dysfunction
This work was supported by National of Institutes of Health grants P01 NS015655 & R01 NS070856, the Michael J. Fox Foundation, and the Department of Veterans Affairs. The authors have no potential conflict of interest relevant to this article to disclose.
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Conflict of Interest
Martijn L.T.M. Müller declares that he has no conflict of interest. Nicolaas I. Bohnen declares that he has no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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