Executive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging

Abstract

Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of EDF in PD. The neurobiological mechanisms of EDF in PD remain poorly understood. Moreover, the treatment of cognitive impairment in PD has progressed slowly and with limited efficacy. Thus, this review explores the characteristics and potential mechanisms of EDF in PD from multiple perspectives, including the concept of executive function, commonly used neuropsychological tests, neurobiochemistry, genetics, electroencephalographic activity and neuroimaging. The available evidence indicates that degeneration of the frontal-striatal circuit, along with mutations in the Catechol-O-methyltransferase (COMT) gene and Leucine-rich repeat kinase 2 (LRRK2) gene, may contribute to EDF in patients with PD. The increase in theta and delta waves, along with the decrease in alpha waves, offers potential biomarkers for the early identification and monitoring of EDF, as well as the development of dementia in patients with PD. The PD cognition-related pattern (PDCP) pattern may serve as a tool for monitoring and assessing cognitive function progression in these patients and is anticipated to become a biomarker for cognitive disorders associated with PD. The aim is to provide new insights for the early and precise diagnosis and treatment of EDF in PD.