Objective: To examine the overlap of genetic architecture for Alzheimer’s disease (AD), schizophrenia (SZ), and PD with the genetic architecture for the occurrence of hallucinations in PD.

Background: Non-motor symptoms, such as hallucinations, among Parkinson’s disease (PD) patients are common. However, the genetic risk factors for hallucinations in PD remain largely elusive.

Method: We used two population-based studies (ParkWest, Norway, and PEG, USA) providing us with 399 PD patients with European ancestry and with a PD diagnosis after age 55 to assess the associations between four polygenic risk scores (PRS) and hallucinations after five years of mean disease duration. Based on existing GWAS of other cohorts, four PRS were created: one each using AD, SZ, and PD cohorts and another PRS for height, which served as a negative control.

Results: A higher prevalence of hallucinations was observed with each standard deviation increase of the AD-PRS (OR: 1.37, 95%CI: 1.03-1.83; P-value 0.03). This effect was mainly driven by APOE (OR: 1.92, 95%CI: 1.14-3.22; P-value 0.01). In addition, a suggestive decrease and increase, respectively, in hallucinations prevalence was observed with the SZ-PRS and the PD-PRS (OR: 0.77, 95%CI: 0.59-1.01; P-value 0.06; and OR: 1.29, 95%CI: 0.95-1.76; P-value 0.11, respectively). No association was observed with the height PRS (OR: 1.00, 95%CI: 0.74-1.35; P-value 0.98).

Conclusion: These results suggest that mechanisms for hallucinations in PD may be driven by the some of the same genetic architecture that leads to cognitive decline in AD, especially by APOE.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-risk-scores-and-hallucinations-in-parkinsons-disease-patients/