Cognitive impairment in Parkinson's disease: A clinical and pathophysiological overview

Cognitive dysfunction in Parkinson's disease (PD) has received increasing attention, and, together with other non-motor symptoms, exert a significant functional impact in the daily lives of patients. This article aims to compile and briefly summarize selected published data about clinical features, cognitive evaluation, biomarkers, and pathophysiology of PD-related dementia (PDD). The literature search included articles indexed in the MEDLINE/PubMed database, published in English, over the last two decades. Despite significant progress on clinical criteria and cohort studies for PD-mild cognitive impairment (PD-MCI) and PDD, there are still knowledge gaps about its exact molecular and pathological basis. Here we overview the scientific literature on the role of functional circuits, neurotransmitter systems (monoaminergic and cholinergic), basal forebrain, and brainstem nuclei dysfunction in PD-MCI. Correlations between neuroimaging and cerebrospinal fluid (CSF) biomarkers, clinical outcomes, and pathological results are described to aid in uncovering the neurodegeneration pattern in PD-MCI and PDD.