The psychosis spectrum in Parkinson disease

Key Points Parkinson disease (PD) psychosis refers to a spectrum of illusions, hallucinations and delusions that occur throughout the disease course Evolving literature highlights the importance of recognizing and treating PD psychosis, and understanding its role as a clinical biomarker of disease stage, distribution and future progression Current evidence points to PD psychosis as a set of symptoms with distinct pathophysiological mechanisms, as opposed to a single pathophysiological symptom with a spectrum of severity The relationship between neuropathology in PD psychosis and in vivo measures of reduced metabolism, functional MRI alterations and cortical volume loss remains unclear Further studies are needed to explore the role of PD medication in unmasking psychosis symptoms, why psychosis symptoms predict worse cognitive outcome, comparisons of psychosis symptoms and mechanisms in different clinical conditions, and development of novel treatments The publication of a consensus definition of Parkinson disease (PD) psychosis in 2007 led to a rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. The authors review this literature and discuss the evolving view of PD psychosis, from distinct classes of symptoms to a continuum progressing over the course of PD. In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors — for example, autonomic dysfunction — that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the trea