Objective: To investigate a possible association between psychosis and prodromal Parkinson’s disease (PD) in a population-based cohort, the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD).

Background: Some case series have suggested that psychosis could occur even before the onset of cardinal motor symptoms of PD. However, few studies have focused on the analysis of psychosis in the general population and its association with the probability of prodromal PD.

Method: This study included HELIAD participants aged ≥65 years without dementia and PD. We defined psychosis as the presence of at least one hallucinatory or delusional feature ascertained using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s Disease scale. We calculated the probability of prodromal PD for every participant at baseline and at 3-year follow-up, according to the International Parkinson and Movement Disorders Society (MDS) research criteria. Associations between psychosis and the probability of prodromal PD were tested using linear regression models adjusted for potential confounders (years of education, socioeconomic status, clinical comorbidities).

Results: Prevalence of psychosis at baseline was 2.8% (50 of 1805) and 6.4% (65 of 1010) at 3 year-follow up. After having excluded individuals with psychosis at baseline, participants who had transitioned to psychosis over the 3-year follow up (57 of 937) had approximately 40% higher probability of prodromal PD (OR [95%CI]: 1.398 [1.003, 1.947], p=0.048) compared to those without psychosis. This association was driven mostly by the non-motor markers of prodromal PD, depression, anxiety disorder, constipation and orthostatic hypotension (p<0.05).

Conclusion: Based on the assessments at the 3-year follow-up, it appears that emerging mild psychotic features evolve in parallel with prodromal PD.  This suggests that such mild psychotic features may be part of the prodromal phase of the disease. The association detected, albeit significant, is characterized by limited statistical power, and needs to be confirmed in longitudinal studies in similar population cohorts. Ideally, such studies would include more details on the psychiatric history of the participants and more longitudinal neuropsychiatric assessments.

References: 1) Subramaniam M et al: Prevalence of psychotic symptoms among older adults in an Asian population. Int Psychogeriatr. 2016; 28:1211-20. 2) Pagonabarraga J et al.: Minor Hallucinations Occur in Drug-Naive Parkinson’s Disease Patients, Even From the Premotor Phase. Mov Disord. 2016; 31:45-52. 3) Basile N. Landis, Pierre R. Burkhard: Phantosmias and Parkinson Disease. Arch Neurol. 2008; 65:1237-1239. 4) Takamura S, et al: Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication. Parkinsonism Relat Disord. 2016; 25:108-9. 5) Navarro-Otano J, et al: Alpha-synuclein aggregates in epicardial fat tissue in living subjects without parkinsonism. Parkinsonism Relat Disord. 2013; 19:27-31. 6) Maraki MI, Yannakoulia M, Stamelou M, et al: Mediterranean diet adherence is related to reduced probability of prodromal Parkinson’s disease. Movement disorders: official journal of the Movement Disorder Society 2019; 34(1):48-57. 7) Berg D, Postuma RB, Adler CH, et al: MDS research criteria for prodromal Parkinson’s disease. Movement disorders: official journal of the Movement Disorder Society. 2015; 30(12):1600-11.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/psychosis-in-prodromal-parkinsons-disease/