The psychosis spectrum in Parkinson disease

Abstract

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 treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.

Figure 1. Regions of cortical atrophy in PD psychosis

The figure summarizes studies that have reported regions of increased atrophy in patients with Parkinson disease (PD) psychosis (defined by visual hallucinations in most studies) compared with PD controls. The results are superimposed on a lateral view of the right hemisphere. The approximate locations of regions of atrophy identified in previous work are indicated by circles annotated by the relevant references. The red regions indicate atrophy in our own study (ffytche, D. et al., unpublished work), in which PD patients with visual hallucinations (n = 8; mean Mini-Mental State Examination (MMSE) score 27.3) were compared with PD controls (n = 9; mean MMSE score 29.6). A lenient statistical threshold (P < 0.01; 100 contiguous voxels) is used for illustrative purposes. Lighter red shading indicates regions deep to the rendered cortical surface. These summary findings indicate that visual hallucinations in PD are associated with widely distributed but specific regions of cortical atrophy.