scholarly journals Mini Review: Correlations of Cognitive Domains With Cerebrospinal Fluid α-Synuclein Levels in Patients With Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hidetomo Murakami ◽  
Kenjiro Ono ◽  
Tomotaka Shiraishi ◽  
Tadashi Umehara ◽  
Shusaku Omoto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Performance ◽  
Lewy Bodies ◽  
Executive Dysfunction ◽  
Cognitive Outcome ◽  
The Other ◽  
Cognitive Domains ◽  
Csf Levels

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

scholarly journals Cerebrospinal fluid biomarkers and cognitive performance in non-demented patients with Parkinson’s disease

2011 ◽  
Vol 17 (1) ◽  
pp. 61-64 ◽  
Author(s):  
James B. Leverenz ◽  
G. Stennis Watson ◽  
Jane Shofer ◽  
Cyrus P. Zabetian ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Performance ◽  
Cerebrospinal Fluid Biomarkers

scholarly journals Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1429-1442
Author(s):  
Marianne von Euler Chelpin ◽  
Linda Söderberg ◽  
Johanna Fälting ◽  
Christer Möller ◽  
Marco Giorgetti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Corticobasal Degeneration ◽  
Alpha Synuclein ◽  
Cross Reactivity ◽  
Potential Biomarker ◽  
Csf Levels

Background: Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. Objective: To develop a novel method to quantify cerebrospinal fluid (CSF) levels of α-synuclein protofibrils (α-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. Methods: A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer’s disease (AD, tau<350 pg/mL, amyloid-beta 42 (Aβ42)>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total α-synuclein (α-syn) levels were analyzed with a commercial ELISA-kit. Results: The assay is specific to α-syn PF, with no cross-reactivity to monomeric α-syn, or the β- and γ-synuclein variants. CSF α-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using α-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total α-syn were significantly different between the PD and CBD groups (p = 0.04). Conclusion: The developed method specifically quantifies α-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.

scholarly journals Cognitive Impact of Deep Brain Stimulation on Parkinson’s Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Raja Mehanna ◽  
Jawad A. Bajwa ◽  
Hubert Fernandez ◽  
Aparna Ashutosh Wagle Shukla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Negative Impact ◽  
Cognitive Outcome ◽  
Cognitive Domains ◽  
The Impact ◽  
Deep Brain

Subthalamic nucleus (STN) or globus pallidus interna (GPi) deep brain stimulation (DBS) is considered a robust therapeutic tool in the treatment of Parkinson’s disease (PD) patients, although it has been reported to potentially cause cognitive decline in some cases. We here provide an in-depth and critical review of the current literature regarding cognition after DBS in PD, summarizing the available data on the impact of STN and GPi DBS as monotherapies and also comparative data across these two therapies on 7 cognitive domains. We provide evidence that, in appropriately screened PD patients, worsening of one or more cognitive functions is rare and subtle after DBS, without negative impact on quality of life, and that there is very little data supporting that STN DBS has a worse cognitive outcome than GPi DBS.

scholarly journals Comparisons of cardiovascular dysautonomia and cognitive impairment between de novo Parkinson’s disease and de novo dementia with Lewy bodies

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hisayoshi Oka ◽  
Tadashi Umehara ◽  
Atsuo Nakahara ◽  
Hiromasa Matsuno
Keyword(s):  
Blood Pressure ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
De Novo ◽  
Blood Pressure Monitoring ◽  
Lewy Bodies ◽  
Executive Dysfunction

Abstract Background Cognitive impairment may be correlated with cardiovascular dysautonomia, including blood pressure (BP) dysregulation, in Parkinson’s disease (PD), but the association between these factors in dementia with Lewy bodies (DLB) is uncertain. This study aimed to clarify whether cardiovascular dysautonomia had an influence on cognitive function in Lewy body disease or not. Methods Ninty-nine patients with de novo PD (n = 75) and DLB (n = 24) were evaluated using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension (PPH), nocturnal BP fall in 24-h ambulatory blood pressure monitoring (ABPM) and constipation were estimated. Associations of these factors with cognitive and executive dysfunction were examined. Results In DLB, MIBG uptake was reduced and OH, PPH and SH were severely disturbed, compared to PD. The nocturnal BP fall in ABPM was lower in DLB, and the failure of nocturnal BP fall in PD was associated with MMSE, after adjustment for other clinical features. FAB was significantly associated nocturnal BP fall, age and SH in PD, but no significant correlations among factors were found for DLB. Conclusion The significant association between nocturnal BP dysregulation and cognitive or executive decline in PD might be due to impaired microvascular circulation or invasion of α-synuclein in the CNS. The lack of a correlation of BP insufficiency with cognitive impairment in DLB suggests initial involvement of Lewy body pathology in the neocortex, regardless of Lewy body invasion of the autonomic nervous system.

scholarly journals Dementia with Lewy bodies and Parkinson’s disease dementia-two independent disorders or one clinical entity within a clinical spectrum of synucleinopathies?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ewa Papuć
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Features ◽  
Dementia With Lewy Bodies ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Executive Dysfunction ◽  
Clinical Entity ◽  
Parkinson’S Disease Dementia ◽  
Visual Spatial

AbstractIntroduction: Introduction: Both dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are important dementia syndromes that overlap in their clinical features and clinical course, neuropathological abnormalities, and also therapeutic approach. Nevertheless it is still unclear whether DLB and PDD are two different disorders that require differentiation or are one clinical entity within a spectrum of Lewy body disease. Currently these disorders are mainly distinguished on the basis of the relative timing of the onset of symptoms of dementia and parkinsonism. The present paper presents current concepts on the pathogenesis of both disorders and their possible overlap.Material and methods: Online databases in the field of DLB and PDD were searched for to find potentially eligible articles. Only most recent articles published after the year 2000 were chosen.Results: The clinical features of DLB and PDD are similar and include dementia with hallucinations and cognitive fluctuations, as well as parkinsonian signs. Also cognitive deficits are similar in PDD and in DLB, with predominance of executive dysfunction, visual-spatial deficits and memory impairment. Neuropathological changes in both disorders involve the presence of Lewy bodies and Lewy neurites within brainstem, limbic and neocortex, as well as loss of midbrain dopamine cells, and loss of cholinergic neurons in the nuclei of ventral forebrain.Conclusions: Similarities in clinical manifestation, neuropsychological deficits and neuropathological abnormalities may suggest that both DLB and PDD are two different phenotypes of the same disorder. This review article presents current knowledge on similarities and differences between these two clinical entities and raises the question whether they require differentiation or not.

scholarly journals HIGHER LEVELS OF CEREBROSPINAL FLUID NITRITE AND NITRATE IN LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE

2020 ◽  
Author(s):  
Bruno L. Santos-Lobato ◽  
Mariza Bortolanza ◽  
Marcelo E. Batalhão ◽  
Ângela V. Pimentel ◽  
Evelin Capellari-Carnio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
List Type ◽  
Healthy Controls ◽  
Clinical Variables ◽  
Csf Levels ◽  
Nitric Oxide Metabolites

AbstractIntroductionLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID.MethodsWe measured CSF NOx levels in patients with PD with and without LID, and in healthy controls. The levels of CSF NOx levels were measured by ozone-based chemiluminescence.Results67 participants were enrolled. CSF NOx levels were higher in patients with PD with LID than in healthy controls (Kruskal-Wallis statistics = 7.24, p = 0.02). CSF NOx levels did not correlate with other clinical variables.ConclusionWe reported higher levels of nitric oxide in the CSF of patients with PD and LID.Highlights–Nitric oxide has a role on levodopa-induced dyskinesias in Parkinson’s disease–We measured CSF nitrite and nitrate in Parkinson’s disease patients with dyskinesias–CSF nitrite and nitrate were higher in Parkinson’s disease patients with dyskinesias

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