scholarly journals Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to visual hallucinations in patients with Parkinson’s and Lewy body diseases

2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Claudio Babiloni ◽  
Susanna Lopez ◽  
Maria Teresa Pascarelli ◽  
Roberta Lizio ◽  
Giuseppe Noce ◽  
...  
Keyword(s):  
Lewy Body ◽  
Visual Hallucinations ◽  
Quiet Wakefulness ◽  
Lewy Body Diseases

scholarly journals Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson’s and Lewy body diseases

2020 ◽  
Vol 16 (S4) ◽  
Author(s):  
Susanna Lopez ◽  
Claudio Del Percio ◽  
Maria Teresa Pascarelli ◽  
Roberta Lizio ◽  
Giuseppe Noce ◽  
...  
Keyword(s):  
Lewy Body ◽  
Visual Hallucinations ◽  
Quiet Wakefulness ◽  
Lewy Body Diseases

scholarly journals Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases

2021 ◽  
Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy M. Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Lewy Body ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Subsequent Development ◽  
Lewy Body Dementia ◽  
Anterior Cingulate ◽  
Lewy Body Diseases

AbstractParkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

scholarly journals The spectrum of cognitive impairment in Lewy body diseases

2014 ◽  
Vol 29 (5) ◽  
pp. 608-621 ◽  
Author(s):  
Jennifer G. Goldman ◽  
Caroline Williams-Gray ◽  
Roger A. Barker ◽  
John E. Duda ◽  
James E. Galvin
Keyword(s):  
Cognitive Impairment ◽  
Lewy Body ◽  
Lewy Body Diseases

scholarly journals Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiki Takamatsu ◽  
Masayo Fujita ◽  
Gilbert J. Ho ◽  
Ryoko Wada ◽  
Shuei Sugama ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Gastrointestinal Symptoms ◽  
Lewy Bodies ◽  
Antagonistic Pleiotropy ◽  
Nonmotor Symptoms ◽  
Novel Therapy ◽  
Wide Range ◽  
Lewy Body Diseases

Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.

Intralaminar nuclei of the thalamus in Lewy body diseases

2009 ◽  
Vol 78 (2-3) ◽  
pp. 97-104 ◽  
Author(s):  
Daniel Brooks ◽  
Glenda M. Halliday
Keyword(s):  
Lewy Body ◽  
Intralaminar Nuclei ◽  
Lewy Body Diseases

The “Sick-but-not-Dead” Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases

2020 ◽  
Vol 40 (05) ◽  
pp. 502-514
Author(s):  
David S. Goldstein
Keyword(s):  
Lewy Body ◽  
Lewy Bodies ◽  
Dopamine Metabolism ◽  
Major Constituent ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Catecholaminergic Neurons ◽  
Disease States ◽  
Dopamine Content ◽  
Lewy Body Diseases

AbstractThe catecholamines dopamine and norepinephrine are key central neurotransmitters that participate in many neurobehavioral processes and disease states. Norepinephrine is also the main neurotransmitter mediating regulation of the circulation by the sympathetic nervous system. Several neurodegenerative disorders feature catecholamine deficiency. The most common is Parkinson's disease (PD), in which putamen dopamine content is drastically reduced. PD also entails severely decreased myocardial norepinephrine content, a feature that characterizes two other Lewy body diseases—pure autonomic failure and dementia with Lewy bodies. It is widely presumed that tissue catecholamine depletion in these conditions results directly from loss of catecholaminergic neurons; however, as highlighted in this review, there are also important functional abnormalities in extant residual catecholaminergic neurons. We refer to this as the “sick-but-not-dead” phenomenon. The malfunctions include diminished dopamine biosynthesis via tyrosine hydroxylase (TH) and L-aromatic-amino-acid decarboxylase (LAAAD), inefficient vesicular sequestration of cytoplasmic catecholamines, and attenuated neuronal reuptake via cell membrane catecholamine transporters. A unifying explanation for catecholaminergic neurodegeneration is autotoxicity exerted by 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in cytoplasmic dopamine metabolism. In PD, putamen DOPAL is built up with respect to dopamine, associated with a vesicular storage defect and decreased aldehyde dehydrogenase activity. Probably via spontaneous oxidation, DOPAL potently oligomerizes and forms quinone-protein adducts with (“quinonizes”) α-synuclein (AS), a major constituent in Lewy bodies, and DOPAL-induced AS oligomers impede vesicular storage. DOPAL also quinonizes numerous intracellular proteins and inhibits enzymatic activities of TH and LAAAD. Treatments targeting DOPAL formation and oxidation therefore might rescue sick-but-not-dead catecholaminergic neurons in Lewy body diseases.

scholarly journals Visuo-Perceptual and Decision-Making Contributions to Visual Hallucinations in Mild Cognitive Impairment in Lewy Body Disease: Insights from a Drift Diffusion Analysis

2020 ◽  
Vol 10 (8) ◽  
pp. 540
Author(s):  
Lauren Revie ◽  
Calum A Hamilton ◽  
Joanna Ciafone ◽  
Paul C Donaghy ◽  
Alan Thomas ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Reaction Time ◽  
Diffusion Model ◽  
Lewy Body ◽  
Drift Rate ◽  
Lewy Body Disease ◽  
Visual Hallucinations ◽  
Drift Diffusion Model ◽  
Drift Diffusion

Background: Visual hallucinations (VH) are a common symptom in dementia with Lewy bodies (DLB); however, their cognitive underpinnings remain unclear. Hallucinations have been related to cognitive slowing in DLB and may arise due to impaired sensory input, dysregulation in top-down influences over perception, or an imbalance between the two, resulting in false visual inferences. Methods: Here we employed a drift diffusion model yielding estimates of perceptual encoding time, decision threshold, and drift rate of evidence accumulation to (i) investigate the nature of DLB-related slowing of responses and (ii) their relationship to visuospatial performance and visual hallucinations. The EZ drift diffusion model was fitted to mean reaction time (RT), accuracy and RT variance from two-choice reaction time (CRT) tasks and data were compared between groups of mild cognitive impairment (MCI-LB) LB patients (n = 49) and healthy older adults (n = 25). Results: No difference was detected in drift rate between patients and controls, but MCI-LB patients showed slower non-decision times and boundary separation values than control participants. Furthermore, non-decision time was negatively correlated with visuospatial performance in MCI-LB, and score on visual hallucinations inventory. However, only boundary separation was related to clinical incidence of visual hallucinations. Conclusions: These results suggest that a primary impairment in perceptual encoding may contribute to the visuospatial performance, however a more cautious response strategy may be related to visual hallucinations in Lewy body disease. Interestingly, MCI-LB patients showed no impairment in information processing ability, suggesting that, when perceptual encoding was successful, patients were able to normally process information, potentially explaining the variability of hallucination incidence.

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