Neuropsychiatric symptoms related to cholinergic deficits in Parkinson’s disease

Abstract

Abstract: Given its ability to explain the most frequent motor symptoms of Parkinson’s disease (PD), degeneration of dopaminergic neurons has been considered one of the disease´s main pathophysiological features. Several studies have shown that neurodegeneration also affects noradrenergic, serotoninergic, cholinergic and other monoaminergic neuronal populations. In this work, the characteristic contribution of cholinergic deficits to cognitive dysfunction, psychosis and sleep disturbances in PD and their treatment will be explored. Important neurophysiological processes at the root of several motor and cognitive functions remit to cholinergic neurotransmission at the synaptic pathway and circuital levels. The bulk of evidence highlights the link between cholinergic alterations and the aforementioned symptoms. The pathophysiology of these symptoms is related to degeneration of cholinergic nuclei, most importantly the nucleus basalis magnocellularis and the pedunculo-pontine nucleus. 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. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Anticholinergic drugs should be used with caution in PD, as they may aggravate these cholinergic symptoms.