Cognitive impairment in advanced Parkinson's disease

Abstract

AbstractCognitive impairment is known to be a non‐motor symptom of Parkinson's disease (PD). Multiple cognitive domains, such as executive, attention, visuoperceptual, and memory functions, are impaired in PD. Various cognitive neural networks should, therefore, be involved in PD. Neural degeneration due to the pathology of Lewy bodies spread to many neural networks, leading to cognitive impairment. Executive dysfunction is mostly related to dopaminergic network disruption, projecting from the nigrostriatal and mesocorticolimbic systems to the prefrontal lobes. This idea was strengthened by the convincing evidence that administrating levodopa can provide beneficial effects for executive functions with improvements in motor symptoms. Frontoparietal cholinergic and noradrenergic network dysfunctions induce attention deficits, including cognitive fluctuation. Abnormality in the cholinergic network is related to visuoperceptual processing dysfunction, which induces visual hallucinations and memory impairments. Pharmacological treatments using cholinesterase inhibitors are effective in improving cognitive function in PD with dementia, which strongly supports the above concept. The pathology of Lewy bodies in the cortical and limbic systems relates to cognitive impairment, and the pathology of cortical amyloids facilitates the progression of cognitive decline in PD. Biomarker studies of cerebrospinal fluid measurements, neuroimaging, and neurophysiology have provided much evidence of cognitive impairment in PD. This review discusses the current knowledge on cognitive impairment in advanced PD, focusing on the distinct neural networks affected by neural degeneration.