Hallucinations in Parkinson’s disease: new insights into mechanisms and treatments

Weil, Rimona S; Reeves, Suzanne

doi:10.47795/onns5189

Cited by 21 publications

(24 citation statements)

References 29 publications

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“…17,18 This has led to the speculation that the emergence of an aberrant top-to-down visual processing system dominating over the usual down-to-top system is perhaps key to the genesis of hallucinations in PD. [19][20][21] In this context, the possibility of a "cortical release" phenomenon has also been speculated in the past which could explain the abnormalities in the executive functions in PD-P group. 22 We observed significant impairment in the visuospatial function (visuospatial working memory, visual memory) in the PD-P group.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Correlates of Visual and Minor Hallucinations in Parkinson’s Disease

Lenka

Hegde

Arumugham

et al. 2021

Can. J. Neurol. Sci.

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Introduction: Psychosis is one of the incapacitating nonmotor symptoms of Parkinson’s disease (PD). Although several risk factors that include older age, rapid eye movement sleep behavior disorder, depression, and cognitive dysfunction have been identified, the exact neural correlates remain elusive. As cognitive impairment has a close association with psychosis in PD, it is useful to know the spectrum of cognitive impairment in PD patients with psychosis (PD-P). Methods: This cross-sectional study compared various cognitive parameters of PD-P (visual/minor hallucinations) and PD patients with no psychosis (PD-NP). A neuropsychological battery encapsulating several cognitive domains (executive, visuospatial, learning, and memory) was used for the cognitive assessment of 37 PD-P and 51 PD-NP patients who were matched for age, gender, education, and disease duration. Results: The two groups were comparable in terms of disease severity and stage. Although the groups had a comparable mean score on Montreal cognitive assessment, the PD-P group performed poorly in tests focused on executive function (color trail test, forward digit span), verbal learning and memory (Rey auditory and verbal learning test), and visuospatial functions (complex figure test, corsi block tapping test). Those with complex visual hallucinations performed poorly in the color trial test (part A) compared to those with minor hallucinations. Conclusion: Psychosis is associated with a multidomain cognitive dysfunction in PD. All PD patients should undergo detailed cognitive assessment as cognitive dysfunction may be a marker of psychosis in the future. Additional longitudinal studies are warranted to obtain detailed insights into this issue.

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Section: Discussionmentioning

confidence: 99%

Cognitive Correlates of Visual and Minor Hallucinations in Parkinson’s Disease

Lenka

Hegde

Arumugham

et al. 2021

Can. J. Neurol. Sci.

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“…In the 'fast'-progressing clusters, the presence of psychotic symptoms in the form of hallucinations or delusions was found as the strongest association. Indeed, hallucinations can already be observed in newly diagnosed patients [19] and experiencing such visual or auditory hallucinations was established to be one of the most notable risk factors for increased mortality [20] and earlier placement in care homes [21]. These findings could, on the one hand, be explained by the difficulties of living with psychosis but, on the other, also point towards a faster disease progression in general.…”

Section: Interpretation Of Significant Associations Between Variables...mentioning

confidence: 99%

Artificial Intelligence-Based Clustering and Characterization of Parkinson’s Disease Trajectories

Birkenbihl

Ahmad

Massat

et al. 2022

Preprint

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Parkinson's disease (PD) is a highly heterogeneous disease both with respect to arising symptoms and its progression over time. This hampers the design of disease modifying trials for PD as treatments which would potentially show efficacy in specific patient subgroups could be considered ineffective in a heterogeneous trial cohort. Establishing clusters of PD patients based on their progression patterns could help to entangle the exhibited heterogeneity, illuminate clinical differences among patient subgroups, and identify the biological pathways and molecular players which underlie the evident differences. Further, stratification of patients into clusters with distinct progression patterns could help to recruit more homogeneous trial cohorts. In the present work, we applied an artificial intelligence-based algorithm to model and cluster longitudinal PD progression trajectories from the Parkinson's Progression Markers Initiative. Using a combination of six clinical outcome scores covering both motor and non-motor symptoms, we were able to identify specific clusters of PD that showed significantly different patterns of PD progression. The inclusion of genetic variants and biomarker data allowed us to associate the established progression clusters with distinct biological mechanisms, such as perturbations in vesicle transport or neuroprotection. Furthermore, we found that patients of identified progression clusters showed significant differences in their responsiveness to symptomatic treatment. Taken together, our work contributes to a better understanding of the heterogeneity encountered when examining and treating patients with PD, and points towards potential biological pathways and genes that could underlie those differences.

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“…Cholinesterase inhibitors may also ameliorate the gait disturbance and risk of falls in PD patients[ 103 ]. Furthermore, compared with PD dementia without psychosis, PD patients with concomitant dementia and psychosis were more likely to benefit from rivastigmine[ 104 , 105 ]. In a randomized, double-blind, placebo-controlled phase II single-center trial, donepezil showed a significant protective effect against the development of psychotic symptoms in PD patients with apolipoprotein E ε4 non-carriers, suggesting that ApoE ε4 allele status may contribute to the resistance of cholinesterase inhibitors[ 106 ].…”

Section: Treatment and Managementmentioning

confidence: 99%

“…In addition to improving cognitive performance, cholinesterase inhibitors may significantly alleviate hallucinations in patients with PD. Because the reported incidence of adverse effects of cholinesterase inhibitors is much lower than that of atypical antipsychotics, cholinesterase inhibitors may be an alternative treatment for improving “benign or minor” hallucinations, especially in PD dementia with psychosis[ 104 ].…”

Section: Treatment and Managementmentioning

confidence: 99%

Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms

Zhang¹,

Ma²

2022

WJP

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. Psychosis is one of the common psychiatric presentations in the natural course of PD. PD psychosis is an important non-motor symptom, which is strongly correlated with a poor prognosis. Increasing attention is being given to PD psychosis. In this opinion review, we summarized and analyzed the identification, screening, epidemiology, mechanisms, risk factors, and therapeutic approaches of PD psychosis based on the current clinical evidence. PD psychosis tends to have a negative effect on patients' quality of life and increases the burden of family caregiving. Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome. Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters, structural and network changes, genetic profiles, cognitive impairment, and antiparkinsonian medications. The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug, antipsychotics, cholinesterase inhibitors, and non-pharmacological interventions. Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis. Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

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Hallucinations in Parkinson’s disease: new insights into mechanisms and treatments

Cited by 21 publications

References 29 publications

Cognitive Correlates of Visual and Minor Hallucinations in Parkinson’s Disease

Cognitive Correlates of Visual and Minor Hallucinations in Parkinson’s Disease

Artificial Intelligence-Based Clustering and Characterization of Parkinson’s Disease Trajectories

Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms

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