Pharmacotherapies for Parkinson’s disease symptoms related to cholinergic degeneration

ABSTRACT

Introduction: 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.

KEYWORDS:

• Parkinson’s disease
• acetylcholine
• cholinergic dysfunction
• neurodegeneration
• treatment
• pathophysiology

Article highlights

• Cholinergic degeneration is widespread in Parkinson’s Disease and may contribute to gait impairments, cognitive impairment, psychosis, or REM-sleep disturbances.

• Cholinesterase inhibitors, which enhance cholinergic tone, have shown some efficacy for the treatment of dementia and gait impairments. Evidence of their effect on psychosis and REM-sleep disturbances is weak. DBS of the PPN nuclei has also been used with some success for the treatment of gait dysfunction.

• Anticholinergic drugs should be used with caution in Parkinson’s Disease, especially in patients with cognitive impairment and/or gait impairments. Nevertheless, in some patients they might help control parkinsonian motor symptoms.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.