Objective: To investigate whether baseline amyloid-β positivity is associated with subsequent development of major hallucination in Parkinson’s disease (PD).

Background: Hallucinations are a major non-motor complication in PD, but early biomarkers predicting their emergence remain unclear. Amyloid-β is a common co-pathology in PD, with its prevalence up to 30% in early stage of PD. Amyloid-β is associated with cognitive decline in PD, but its contribution to psychosis remains elusive.

Method: We analyzed participants from the Parkinson’s Progression Markers Initiative with early PD. Major hallucination was defined as a score of ≥ 2 on the hallucination/psychosis item of the MDS-UPDRS part I during follow-up. Time-to-event analysis was performed using Kaplan-Meier curve and multivariate Cox proportional hazard model, adjusted for age, sex, education, APOE4 status, baseline MoCA score, and caudate dopaminergic availability.

Results: A total of 401 patients were included, of whom 71 (17.7%) were amyloid-positive at baseline. Amyloid-positive patients were older and more likely to carry APOE4. Kaplan-Meier analysis showed a higher risk of major hallucinations in the amyloid-beta positive group than in the negative group (plog-rank < 0.0001). In the adjusted Cox model, baseline amyloid positivity was associated with increased risk of future major hallucinations (hazard ratio 3.82, 95% confidence interval 2.23 – 6.52, p < 0.001), independent of baseline MoCA and caudate dopamine transporter availability.

Conclusion: Baseline CSF amyloid positivity is strong independent predictor of incident major hallucinations in PD, independent of dopaminergic denervation and overall cognition. These findings suggest that amyloid-beta co-pathology may contribute to early psychosis-related vulnerability.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-amyloid-beta-co-pathology-on-future-hallucination-in-parkinsons-disease/