scholarly journals Cortical Lewy Body Dementia

1990 ◽  
Vol 3 (3) ◽  
pp. 189-196 ◽  
Author(s):  
W. R. G. Gibb

In cortical Lewy body dementia the distribution of Lewy bodies in the nervous system follows that of Parkinson's disease, except for their greater profusion in the cerebral cortex. The cortical tangles and plaques of Alzheimer pathology are often present, the likely explanation being that Alzheimer pathology provokes dementia in many patients. Pure cortical Lewy body dementia without Alzheimer pathology is uncommon. The age of onset reflects that of Parkinson's disease, and clinical features, though not diagnostic, include aphasias, apraxias, agnosias, paranoid delusions and visual hallucinations. Parkinsonism may present before or after the dementia, and survival duration is approximately half that seen in Parkinson's disease without dementia.

Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy M. Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  

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.


BJPsych Open ◽  
2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Ajenthan Surendranathan ◽  
Joseph P. M. Kane ◽  
Allison Bentley ◽  
Sally A. H. Barker ◽  
John-Paul Taylor ◽  
...  

Background Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series. Aims This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences. Method We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions. Results The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs. Conclusions Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.


2021 ◽  
Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  

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.


2009 ◽  
Vol 4 (1) ◽  
pp. 32 ◽  
Author(s):  
Bo Su ◽  
Haihua Liu ◽  
Xinglong Wang ◽  
Shu G Chen ◽  
Sandra L Siedlak ◽  
...  

2013 ◽  
Vol 27 (4) ◽  
pp. 479-493 ◽  
Author(s):  
M. Onofrj ◽  
J. P. Taylor ◽  
D. Monaco ◽  
R. Franciotti ◽  
F. Anzellotti ◽  
...  

Visual Hallucinations (VH) are a common non-motor symptom of Parkinson’s Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance.More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery.Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH.We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.


Author(s):  
Maarten C Hardenberg ◽  
Tessa Sinnige ◽  
Sam Casford ◽  
Samuel Dada ◽  
Chetan Poudel ◽  
...  

Abstract Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy body formation remains unclear. Here we show, both in vitro and in a Caenorhabditis elegans model of Parkinson’s disease, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.


2008 ◽  
Vol 2 (4) ◽  
pp. 261-266
Author(s):  
Jorge Lorenzo Otero

Abstract Dementia with Parkinson's disease represents a controversial issue in the complex group of alpha-synucleinopathies. The author acknowledges the concept of a "continuum" between Parkinson disease's (PD), Lewy body dementia (LBD), and dementia in Parkinson's disease (PDD). However, the practicing neurologist needs to identify the phenotypic signs of each dementia. The treatment and prognosis are different in spite of the overlaps between them. The main aim of this review was to characterize the clinical diagnoses of dementia associated with Parkinson's disease (PDD). Secondarily, the review discussed some epidemiological and neuropsychological issues. Selection of articles was not systematic and reflects the author's opinion, where the main text selected was the recommendations from the Movement Disorder Society Task Force for PDD diagnosis. The Pub Med, OVID, and Proquest data bases were used for the search.


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