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Sleep Medicine Jan 2023The glymphatic system is thought to be responsible for waste clearance in the brain. As it is primarily active during sleep, different components of sleep, subjective... (Review)
Review
OBJECTIVE
The glymphatic system is thought to be responsible for waste clearance in the brain. As it is primarily active during sleep, different components of sleep, subjective sleep quality, and sleep patterns may contribute to glymphatic functioning. This systematic review aimed at exploring the effect of sleep components, sleep quality, and sleep patterns on outcomes associated with the glymphatic system in healthy adults.
METHODS
PubMed®, Scopus, and Web of Science were searched for studies published in English until December 2021. Articles subjectively or objectively investigating sleep components (total sleep time, time in bed, sleep efficiency, sleep onset latency, wake-up after sleep onset, sleep stage, awakenings), sleep quality, or sleep pattern in healthy individuals, on outcomes associated with glymphatic system (levels of amyloid-β, tau, α-synuclein; cerebrospinal fluid, perivascular spaces; apolipoprotein E) were selected.
RESULTS
Out of 8359 records screened, 51 studies were included. Overall, contradictory findings were observed according to different sleep assessment method. The most frequently assessed sleep parameters were total sleep time, sleep quality, and sleep efficiency. No association was found between sleep efficiency and amyloid-β, and between slow-wave activity and tau. Most of the studies did not find any correlation between total sleep time and amyloid-β nor tau level. Opposing results correlated sleep quality with amyloid-β and tau.
CONCLUSIONS
This review highlighted inconsistent results across the studies; as such, the specific association between the glymphatic system and sleep parameters in healthy adults remains poorly understood. Due to the heterogeneity of sleep assessment methods and the self-reported data representing the majority of the observations, future studies with universal study design and sleep methodology in healthy individuals are advocated.
Topics: Adult; Humans; Amyloid beta-Peptides; Brain; Glymphatic System; Sleep; Sleep Wake Disorders
PubMed: 36481512
DOI: 10.1016/j.sleep.2022.11.012 -
Frontiers in Immunology 2021Parkinson's disease (PD) is one of most common neurodegenerative disorders caused by a combination of environmental and genetic risk factors. Currently, numerous...
Parkinson's disease (PD) is one of most common neurodegenerative disorders caused by a combination of environmental and genetic risk factors. Currently, numerous population genetic studies have shown that polymorphisms in myeloid cell-triggered receptor II (TREM2) are associated with a variety of neurodegenerative disorders. Recently, TREM2 has been verified to represent a promising candidate gene for PD susceptibility and progression. For example, the expression of TREM2 was apparently increased in the prefrontal cortex of PD patients. Moreover, the rare missense mutations in TREM2 (rs75932628, p.R47H) was confirmed to be a risk factor of PD. In addition, overexpression of TREM2 reduced dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of PD. Due to the complex pathogenesis of PD, there is still no effective drug treatment. Thus, TREM2 has received increasing widespread attention as a potential therapeutic target. This review focused on the variation of TREM2 in PD and roles of TREM2 in PD pathogenesis, such as excessive-immune inflammatory response, α-Synuclein aggregation and oxidative stress, to further provide evidence for new immune-related biomarkers and therapies for PD.
Topics: Animals; Disease Models, Animal; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunotherapy; Membrane Glycoproteins; Mice; Molecular Targeted Therapy; Mutation, Missense; Parkinson Disease; Polymorphism, Genetic; Receptors, Immunologic
PubMed: 35003116
DOI: 10.3389/fimmu.2021.795036 -
European Journal of Nuclear Medicine... Jul 2020Imperfect clinical reference standards can preclude accurately estimating the diagnostic accuracy of DAT-SPECT and MIBG myocardial scintigraphy for diagnosing DLB. To... (Meta-Analysis)
Meta-Analysis
PURPOSE
Imperfect clinical reference standards can preclude accurately estimating the diagnostic accuracy of DAT-SPECT and MIBG myocardial scintigraphy for diagnosing DLB. To investigate the validity of unadjusted accuracy, we updated our previous meta-analysis.
METHODS
Literature search was updated to March 18, 2018. We also examined published systematic review reports. Two investigators extracted data and rated study validity using the QUADAS-2 tool. We performed a Bayesian latent class model meta-analysis accounting for imperfect reference standards.
RESULTS
We evaluated 27 studies including 2236 patients. With the exception of two DAT-SPECT studies that involved postmortem neuropathological verification, studies were susceptible to bias from imperfect reference standards. Compared with the unadjusted accuracy estimates, the adjusted sensitivity values were similar, whereas the adjusted specificity values were generally lower for detecting α-synuclein pathology in the brain. The adjusted summary sensitivity and specificity were 0.86 (95% credible interval [CrI], 0.76-0.95) and 0.81 (CrI, 0.70-0.92), and 0.93 (CrI, 0.74-1.00) and 0.75 (CI, 0.47-0.94) for visual and semi-quantitative assessments of DAT-SPECT, respectively; 0.92 (CrI, 0.81-0.99) and 0.80 (CrI, 0.67-0.93), and 0.87 (CrI, 0.74-0.98) and 0.80 (CrI, 0.69-0.93), for delayed- and early-phase scans of MIBG scintigraphy, respectively. When diagnosing the typical clinical syndrome, the adjusted accuracy values were similar to the unadjusted estimates. The adjusted sensitivity and specificity were 0.89 (CrI, 0.75-0.98) and 0.87 (CrI, 0.72-0.97), and 0.97 (CrI, 0.78-1.0) and 0.70 (CrI, 0.43-0.92) for visual and semi-quantitative assessments of DAT-SPECT, respectively; and 0.93 (CrI, 0.81-0.98) and 0.90 (CrI, 0.73-0.97), and 0.85 (CrI, 0.66-0.96) and 0.96 (95% CI, 0.83-1.0) for delayed- and early-phase scans of MIBG scintigraphy, respectively.
CONCLUSIONS
In our adjusted analyses, both imaging biomarkers had high diagnostic accuracy for detecting the hallmark pathology in the brain and for diagnosing the typical clinical syndrome.
Topics: 3-Iodobenzylguanidine; Bayes Theorem; Humans; Latent Class Analysis; Lewy Body Disease; Radionuclide Imaging; Tomography, Emission-Computed, Single-Photon
PubMed: 31423561
DOI: 10.1007/s00259-019-04480-8 -
Frontiers in Aging Neuroscience 2022Parkinson's disease (PD) is one of the common neurodegenerative diseases that is characterized by selective degeneration of dopaminergic neurons in the substantia nigra,...
Parkinson's disease (PD) is one of the common neurodegenerative diseases that is characterized by selective degeneration of dopaminergic neurons in the substantia nigra, and misfolding of α-synuclein into aggregates is thought to contribute to its pathology. Studies have shown that immune-inflammatory responses are involved in the development of PD and play an important role in α-synuclein scavenge. Natural killer (NK) cells are first responders in immune cells and can directly promote immune defense mechanisms by cytotoxicity and by secreting cytokines. Recent discoveries suggest that NK cells are increasingly recognized in the pathological features of PD. However, the mechanisms underlying it have not been fully understood. In this review, we systematically retrieved and evaluated published evidence about the functions of NK cells in PD. We find alterations in the number of NK cells and cytotoxicity during the progression of PD, and it seems that NK cells play a neuroprotective role in PD pathogenesis, which may further reveal novel targets for the management and treatment of PD.
PubMed: 35663564
DOI: 10.3389/fnagi.2022.890816 -
Geriatrie Et Psychologie... Dec 2021Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinsonian dementia (PD), which follows the evolution of Parkinson disease....
BACKGROUND
Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinsonian dementia (PD), which follows the evolution of Parkinson disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the fact that the disease has only recently been described and the first international diagnostic criteria have only recently been published (1996).
METHOD
This article proposes a synthesis of the therapeutic trials carried out into DLB in the last five years, including PD patients, using the Clinicaltrials.gov and Pubmed.gov databases.
RESULTS
We identified 35 therapeutic trials on ClinicalTrials.gov and 14 on PubMed. In line with our temporal criteria, 21 trials were analysed. Of the 11 completed trials with reported results, two drugs showed positive results: two trials with zonisamide (phases 2 and 3) showed improvements in Parkinsonian syndrome and one trial with neflamapimod (phase 2) showed improvements in cognition and walking.
CONCLUSION
In recent years, there has been an increase in therapeutic research into DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, although the proportion of positive trials is significant. Effective treatment to modify the course of the disease would have significant consequences for patients and their relatives.
PubMed: 34933841
DOI: 10.1684/pnv.2021.0981 -
CNS Neuroscience & Therapeutics Feb 2019Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy...
AIMS
Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction.
DISCUSSION
Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia.
CONCLUSION
A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.
Topics: Adult; Aged; Antiparkinson Agents; Child; Humans; Parkinsonian Disorders
PubMed: 30294976
DOI: 10.1111/cns.13068 -
Journal of the Neurological Sciences Aug 2020Frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) are two common forms of neurodegenerative dementia, subsequent to Alzheimer's disease (AD). AD is the... (Review)
Review
RATIONALE
Frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) are two common forms of neurodegenerative dementia, subsequent to Alzheimer's disease (AD). AD is the only dementia that includes clinically validated cerebrospinal fluid (CSF) biomarkers in the diagnostic criteria. FTD and DLB often overlap with AD in their clinical and pathological features, making it challenging to differentiate between these conditions.
AIM
This systematic review aimed to identify if novel fluid biomarkers are useful in differentiating FTD and DLB from AD. Increasing the certainty of the differentiation between dementia subtypes would be advantageous clinically and in research.
METHODS
PubMed and Scopus were searched for studies that quantified and assessed diagnostic accuracy of novel fluid biomarkers in clinically diagnosed patients with FTD or DLB, in comparison to patients with AD. Meta-analyses were performed on biomarkers that were quantified in 3 studies or more.
RESULTS
The search strategy yielded 614 results, from which, 27 studies were included. When comparing bio-fluid levels in AD and FTD patients, neurofilament light chain (NfL) level was often higher in FTD, whilst brain soluble amyloid precursor protein β (sAPPβ) was higher in patients with AD. When comparing bio-fluid levels in AD and DLB patients, α-synuclein ensued heterogeneous findings, while the noradrenaline metabolite (MHPG) was found to be lower in DLB. Ratios of Aβ42/Aβ38 and Aβ42/Aβ40 were lower in AD than FTD and DLB and offered better diagnostic accuracy than raw amyloid-β (Aβ) concentrations.
CONCLUSIONS
Several promising novel biomarkers were highlighted in this review. Combinations of fluid biomarkers were more often useful than individual biomarkers in distinguishing subtypes of dementia. Considering the heterogeneity in methods and results between the studies, further validation, ideally with longitudinal prospective designs with large sample sizes and unified protocols, are fundamental before conclusions can be finalised.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Frontotemporal Dementia; Humans; Lewy Body Disease; Peptide Fragments; Prospective Studies; tau Proteins
PubMed: 32428759
DOI: 10.1016/j.jns.2020.116886 -
Heliyon Mar 2023The aim of this study was to evaluate the effects of probiotics on the treatment of constipation in patients with Parkinson's disease (PD) by analyzing data from... (Review)
Review
OBJECTIVES
The aim of this study was to evaluate the effects of probiotics on the treatment of constipation in patients with Parkinson's disease (PD) by analyzing data from published randomized clinical trials (RCTs). PD is a neurodegenerative disease characterized by clinical symptoms such as rigidity, bradykinesia, and resting tremor. Constipation is a common complaint reported by PD patients. Probiotics are often used to treat functional constipation. The potential mechanisms behind PD-related constipation include dysfunction of the enteric nervous system due to alpha-synuclein aggregation, dyssynergic contractions of the puborectalis muscle, and alterations of the gut microbiome.
METHOD
To conduct this study, we searched Scopus, PubMed, and Google Scholar for published articles on PD, probiotics, and constipation. We selected RCTs from 944 studies, and ultimately included 3 RCTs in our meta-analysis. The frequency of bowel movements per week was the only index that could be summarized among the records. We extracted and analyzed the results as means and standard deviations.
RESULT
We calculated a standardized mean difference (SMD) of 0.92 (95% CI, 0.65 to 1.19; I-squared = 57.0%; p < 0.001) to determine the treatment effect in terms of frequency of bowel movements per week in the RCTs.
CONCLUSION
Our results show that probiotic intake has beneficial effects on constipation in PD patients. Further research, including multicenter studies, is needed to assess the long-term efficacy and safety of probiotic supplements in neurodegenerative diseases.
PubMed: 36938477
DOI: 10.1016/j.heliyon.2023.e14312 -
European Journal of Neurology Feb 2020The aim was to review the existing reports on cognitive and behavioural symptoms in monogenic forms of Parkinson's disease (PD) and to identify recurring patterns of...
The aim was to review the existing reports on cognitive and behavioural symptoms in monogenic forms of Parkinson's disease (PD) and to identify recurring patterns of clinical manifestations in those with specific mutations. A systematic literature search was conducted to retrieve observational studies of monogenic PD. Data pertaining to cognitive and psychiatric manifestations were extracted using standardized templates. The PRISMA guidelines were followed. Of the 1889 citations retrieved, 95 studies on PD-related gene mutations were included: 35 in SNCA, 35 in LRRK2, four in VPS35, 10 in Parkin, three in DJ1 and eight in PINK1. Nineteen studies (20%) provided adequate data from comprehensive cognitive assessment and 31 studies (32.6%) outlined psychiatric manifestations through the use of neuropsychiatric scales. Cognitive impairment was reported in all monogenic PD forms with variable rates (58.8% PINK1, 53.9% SNCA, 50% DJ1, 29.2% VPS35, 15.7% LRRK2 and 7.4% Parkin). In this regard, executive functions and attention were the domains most affected. With respect to psychiatric symptoms, depression was the most frequent symptom, occurring in 37.5% of PINK1 cases and 41.7% of VPS35 and LRRK2 cases. Co-occurrence of cognitive decline with visual hallucinations was evidenced. Widespread accumulation of Lewy bodies, distinctive of SNCA, PINK1 and DJ1 mutations, results in higher rates of cognitive impairment. Similarly, a higher degree of visual hallucinations is observed in SNCA mutations, probably owing to the more widespread accumulation. The lower rates of α-synuclein pathology in LRRK2 and Parkin may underpin the more benign disease course in these patients.
Topics: Cognition Disorders; Humans; Mental Disorders; Parkinson Disease
PubMed: 31686421
DOI: 10.1111/ene.14115 -
Brain Sciences Apr 2020The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate... (Review)
Review
The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, -GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs.
PubMed: 32290481
DOI: 10.3390/brainsci10040232