Potential Risk Factors for Psychosis in Parkinson’s Disease: A Review of Cohort and Case-Control Studies

Abstract

Background

Among neuropsychiatric sequelae of Parkinson’s disease (PD), psychosis may have the most adverse impacts on prognosis and quality of life.

Objectives

To summarize and critically review the literature on potential risk factors for psychosis in PD, with particular focus on potentially modifiable risk factors.

Methods

We conducted a literature review using PubMed and EMBASE. We included articles if: (1) the study population was comprised of patients with PD, (2) the presence of psychosis was systematically ascertained through clinician diagnosis, clinical outcome assessments and/or administrative data, and (3) potential risk factors were examined prior to the onset of psychosis.

Results

Twenty-six studies (15 prospective cohort, 10 retrospective cohort, 1 retrospective case-control) of 21 patient cohorts (n = 15,535 unique patients) were included in the review. Ten studies included minor phenomena in their definition of psychosis. The most consistent potential risk factors for psychosis were sleep disturbances, particularly rapid eye movement sleep behavior disorder and autonomic dysfunction. Potentially modifiable risk factors for psychosis included excessive daytime sleepiness and exposure to anticholinergic medications and levodopa. Possible biomarkers for psychosis in PD included reduced striatal dopamine transporter binding on imaging and mutations in the GBA gene.

Conclusions

Several studies have identified potentially modifiable risk factors for the development of psychosis in PD. Future studies should utilize consistent, validated definitions of psychosis and focus on increasing understanding of, and developing interventions for, potentially modifiable risk factors for psychosis in patients with PD.