A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia

Aarsland, Dag; Ballard, Clive; Larsen, Jan Petter; McKeith, Ian G.

doi:10.1002/gps.389

Cited by 296 publications

(210 citation statements)

References 36 publications

(48 reference statements)

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“…Their hallmark is AS pathology manifested as LBs or a variable mixture of AS and AD pathologies, which may interact synergistically [690][691][692]. Both cortical and subcortical AS pathologies have been suggested to be the main determinant [693,694], whereas others suggested AD pathology to be more important, particularly when the Aβ load may be similar to that in AD [695]. The severity and extent of AS are variable, and according to revised guidelines are scored semiquantitatively in specific brain areas [593,[696][697][698][699].…”

Section: Relationship Between α-Synuclein and Lewy Pathologymentioning

confidence: 99%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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Genetic, neuropathological and biochemical evidence implicates α-synuclein, a 140 amino acid presynaptic neuronal protein, in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. The aggregated protein inclusions mainly containing aberrant α-synuclein are widely accepted as morphological hallmarks of α-synucleinopathies, but their composition and location vary between disorders along with neuronal networks affected. α-Synuclein exists physiologically in both soluble and membran-bound states, in unstructured and α-helical conformations, respectively, while posttranslational modifications due to proteostatic deficits are involved in β-pleated aggregation resulting in formation of typical inclusions. The physiological function of α-synuclein and its role linked to neurodegeneration, however, are incompletely understood. Soluble oligomeric, not fully fibrillar α-synuclein is thought to be neurotoxic, main targets might be the synapse, axons and glia. The effects of aberrant α-synuclein include alterations of calcium homeostasis, mitochondrial dysfunction, oxidative and nitric injuries, cytoskeletal effects, and neuroinflammation. Proteasomal dysfunction might be a common mechanism in the pathogenesis of neuronal degeneration in α-synucleinopathies. However, how α-synuclein induces neurodegeneration remains elusive as its physiological function. Genome wide association studies demonstrated the important role for genetic variants of the SNCA gene encoding α-synuclein in the etiology of Parkinson's disease, possibly through effects on oxidation, mitochondria, autophagy, and lysosomal function. The neuropathology of synucleinopathies and the role of α-synuclein as a potential biomarker are briefly summarized. Although animal models provided new insights into the pathogenesis of Parkinson disease and multiple system atrophy, most of them do not adequately reproduce the cardinal features of these disorders. Emerging evidence, in addition to synergistic interactions of α-synuclein with various pathogenic proteins, suggests that prionlike induction and seeding of α-synuclein could lead to the spread of the pathology and disease progression. Intervention in the early aggregation pathway, aberrant cellular effects, or secretion of α-synuclein might be targets for neuroprotection and disease-modifying therapy.

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Section: Relationship Between α-Synuclein and Lewy Pathologymentioning

confidence: 99%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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“…Psychosis is consistently more common in PD patients with dementia, 7,9,11,[19][20][21] and cognitive impairment is a risk factor for later developing hallucinations. 9,22,23 Based on this, many studies have evaluated whether certain cognitive domains are preferentially impaired in PD patients with visual hallucinations.…”

Section: Cognitive and Visual Impairmentmentioning

confidence: 99%

Risk Factors for Psychosis in Parkinson’s Disease

Barrett

2017

US Neurology

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Psychosis is a characteristic neuropsychiatric symptom of Parkinson's disease (PD) that is common and associated with worse outcomes. The purpose of this article is to review identified risk factors for visual hallucinations in PD, the most common manifestation of psychosis. With the possible exception of dopamine agonists, antiparkinsonian medications are only considered modifiers of psychosis in PD. Dementia in PD has consistently been shown to be associated with psychosis, and executive dysfunction and impairment in visual processing appear to play a role in its pathogenesis. The association of psychosis with disorders of sleep-wake dysregulation and autonomic dysfunction supports the involvement of brainstem dysfunction in PD psychosis. Despite many studies evaluating genetic risk factors for hallucinations, GBA mutations are the only variants consistently reported to be associated with an increased risk of hallucinations in PD. Lastly, psychosis in PD is associated with a more severe disease burden, both related and unrelated to PD pathology. Any explanatory model of psychosis in PD must incorporate pharmacological, neuroanatomic, pathological, and genetic factors before there can be a complete understanding of this common and disabling neuropsychiatric symptom. KeywordsParkinson's disease, psychosis, hallucinations, risk factor, dementia, rapid eye movement (REM) sleep behavior disorder Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. had minor hallucinations prior to PD motor symptom onset.3 In addition to being common, psychosis is also associated with worse outcomes: increased institutionalization, 4 decreased quality of life, 5 and increased mortality. Considering its prevalence and association with worse outcomes, many studies have sought to identify risk factors for psychosis, specifically visual hallucinations. These efforts have contributed to an improved understanding of this disabling neuropsychiatric symptom. Some risk factors, i.e. cognitive impairment and rapid eye movement (REM) sleep behavior disorder (RBD), may be integral to the mechanism by which psychotic symptoms emerge and have contributed to development of explanatory models of psychotic symptoms in PD. Other risk factors likely represent correlations arising from concomitant pathology in areas not involved in psychosis but occurring at a similar disease stage. Lastly, multiple studies have helped to clarify the relationship between antiparkinsonian medications, especially dopaminergic medications, and psychosis in PD.The purpose of this article is to review risk factors fo...

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“…Psychotic symptoms were rarely described in idiopathic PD until LDopa was introduced [15]. Because of the clinical and pathological overlap between Dementia with Lewy Bodies (DLB) and PD [16] experts currently argue as to whether these are two separate disorders or not. While DLB had initially been considered "the Lewy body variant of Alzheimer's disease," it is now, more appropriately thought of as a variant of PD.…”

Section: Introductionmentioning

confidence: 99%

“…While DLB had initially been considered "the Lewy body variant of Alzheimer's disease," it is now, more appropriately thought of as a variant of PD. Since one of the cardinal features of DLB is visual hallucinations (VH) [16,17], it is reasonable to wonder whether some psychotic symptoms seen in treated PD patients may be intrinsic to the disease and not related to medications [11]. One report on patients with advanced but untreated PD indicates that psychotic symptoms may occur without dementia [18].…”

Section: Introductionmentioning

confidence: 99%

Parkinson Disease Psychosis: Update

Friedman

2013

Behavioural Neurology

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Abstract. Psychotic symptoms are common in drug treated patients with Parkinson's disease (PD). Visual hallucinations occur in about 30% and delusions, typically paranoid in nature, occur in about 5%. These problems, particularly the delusions, cause great distress for patient and caregivers, and are among the most important precipitants for nursing home placement. Psychotic symptoms carry a poor prognosis. They often herald dementia, and are associated with increased mortality. These symptoms often abate with medication reductions, but this may not be tolerated due to worsened motor function. Only clozapine has level A evidence to support its use in PD patients with psychosis (PDP), whether demented or not. While quetiapine has been recommended by the American Academy of Neurology for "consideration," double blind placebo controlled trials have demonstrated safety but not efficacy. Other antipsychotic drugs have been reported to worsen motor function and data on the effectiveness of cholinesterase inhibitors is limited. PDP remains a serious problem with limited treatment options.

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A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia

Cited by 296 publications

References 36 publications

The role of α-synuclein in neurodegeneration — An update

The role of α-synuclein in neurodegeneration — An update

Risk Factors for Psychosis in Parkinson’s Disease

Parkinson Disease Psychosis: Update

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