The involvement of the cholinergic system in Parkinson disease

In Parkinson disease (PD), cholinergic dysfunction develops in the early stages of the neurodegenerative process and progresses over time. Basal forebrain cholinergic system dysfunction is historically linked to cognitive decline in the dementia spectrum, and its pathophysiologic role in PD-related cognitive impairment has now been well established. However, cholinergic system dysfunction is also linked to several other manifestations of PD, such as gait difficulties, REM sleep behavior disorder (RBD), neuropsychiatric manifestations such as depression and visual hallucinations, and olfactory dysfunction. Furthermore, disruption of the striatal intrinsic cholinergic system, which modulates dopamine release, has been linked to cardinal motor manifestations and dyskinesia. Manifestations of cognitive decline, gait problems, falls, and RBD tend to cluster in a subset of people with PD, so that a "cholinergic phenotype" has been proposed. In this chapter, the involvement of the cholinergic system and its clinical correlates in PD will be discussed.