Pharmacotherapies for Parkinson's disease symptoms related to cholinergic degeneration

Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion: Rivastigmine, a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase, is effective for dementia, whereas the use of Donepezil is still in the realm of investigation. Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.