Levodopa/Carbidopa Intestinal Gel for Treatment of Advanced Parkinson’s Disease: An Update on the Effects of Cognitive Functions

摘要

Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.