Risk Factors for Psychosis in Parkinson’s Disease

Abstract

Psychosis is a characteristic neuropsychiatric symptom of Parkinson's disease (PD) that is common and associated with worse outcomes. The purpose of this article is to review identified risk factors for visual hallucinations in PD, the most common manifestation of psychosis. With the possible exception of dopamine agonists, antiparkinsonian medications are only considered modifiers of psychosis in PD. Dementia in PD has consistently been shown to be associated with psychosis, and executive dysfunction and impairment in visual processing appear to play a role in its pathogenesis. The association of psychosis with disorders of sleep-wake dysregulation and autonomic dysfunction supports the involvement of brainstem dysfunction in PD psychosis. Despite many studies evaluating genetic risk factors for hallucinations, GBA mutations are the only variants consistently reported to be associated with an increased risk of hallucinations in PD. Lastly, psychosis in PD is associated with a more severe disease burden, both related and unrelated to PD pathology. Any explanatory model of psychosis in PD must incorporate pharmacological, neuroanatomic, pathological, and genetic factors before there can be a complete understanding of this common and disabling neuropsychiatric symptom. KeywordsParkinson's disease, psychosis, hallucinations, risk factor, dementia, rapid eye movement (REM) sleep behavior disorder Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. had minor hallucinations prior to PD motor symptom onset.3 In addition to being common, psychosis is also associated with worse outcomes: increased institutionalization, 4 decreased quality of life, 5 and increased mortality. Considering its prevalence and association with worse outcomes, many studies have sought to identify risk factors for psychosis, specifically visual hallucinations. These efforts have contributed to an improved understanding of this disabling neuropsychiatric symptom. Some risk factors, i.e. cognitive impairment and rapid eye movement (REM) sleep behavior disorder (RBD), may be integral to the mechanism by which psychotic symptoms emerge and have contributed to development of explanatory models of psychotic symptoms in PD. Other risk factors likely represent correlations arising from concomitant pathology in areas not involved in psychosis but occurring at a similar disease stage. Lastly, multiple studies have helped to clarify the relationship between antiparkinsonian medications, especially dopaminergic medications, and psychosis in PD.The purpose of this article is to review risk factors fo...