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.