-
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159 -
Journal of Thoracic Disease Aug 2023The sleep onset process is an ill-defined complex process of transition from wakefulness to sleep, characterized by progressive modifications at the subjective,... (Review)
Review
BACKGROUND
The sleep onset process is an ill-defined complex process of transition from wakefulness to sleep, characterized by progressive modifications at the subjective, behavioural, cognitive, and physiological levels. To this date, there is no international consensus which could aid a principled characterisation of this process for clinical research purposes. The current review aims to systemise the current knowledge about the underlying mechanisms of the natural heterogeneity of this process.
METHODS
In this systematic review, studies investigating the process of the sleep onset from 1970 to 2022 were identified using electronic database searches of PsychINFO, MEDLINE, and Embase.
RESULTS
A total of 139 studies were included; 110 studies in healthy participants and 29 studies in participants with sleep disorders. Overall, there is a limited consensus across a body of research about what distinct biomarkers of the sleep onset constitute. Only sparse data exists on the physiology, neurophysiology and behavioural mechanisms of the sleep onset, with majority of studies concentrating on the non-rapid eye movement stage 2 (NREM 2) as a potentially better defined and a more reliable time point that separates sleep from the wake, on the sleep wake continuum.
CONCLUSIONS
The neurophysiologic landscape of sleep onset bears a complex pattern associated with a multitude of behavioural and physiological markers and remains poorly understood. The methodological variation and a heterogenous definition of the wake-sleep transition in various studies to date is understandable, given that sleep onset is a process that has fluctuating and ill-defined boundaries. Nonetheless, the principled characterisation of the sleep onset process is needed which will allow for a greater conceptualisation of the mechanisms underlying this process, further influencing the efficacy of current treatments for sleep disorders.
PubMed: 37691675
DOI: 10.21037/jtd-23-325 -
Brazilian Journal of Cardiovascular... Jul 2023People with type 2 diabetes mellitus present multiple complications and comorbidities, such as peripheral autonomic neuropathies and reduced peripheral force and... (Review)
Review
INTRODUCTION
People with type 2 diabetes mellitus present multiple complications and comorbidities, such as peripheral autonomic neuropathies and reduced peripheral force and functional capacity. Inspiratory muscle training is a widely used intervention with numerous benefits for various disorders. The present study aimed to conduct a systematic review to identify inspiratory muscle training effects on functional capacity, autonomic function, and glycemic indexes in patients with type 2 diabetes mellitus.
METHODS
A search was carried out by two independent reviewers. It was performed in PubMed®, Cochrane Library, Latin American and Caribbean Literature in Health Sciences (or LILACS), Physiotherapy Evidence Database (PEDro), Embase, Scopus, and Web of Science databases. There were no restrictions of language or time. Randomized clinical trials of type 2 diabetes mellitus with inspiratory muscle training intervention were selected. Studies' methodological quality was assessed using PEDro scale.
RESULTS
We found 5,319 studies, and six were selected for qualitative analysis, which was also conducted by the two reviewers. Methodological quality varied - two studies were classified as high quality, two as moderate quality, and two as low quality.
CONCLUSION
It was found that after inspiratory muscle training protocols, there was a reduction in the sympathetic modulation and an increase in functional capacity. The results should be carefully interpreted, as there were divergences in the methodologies adopted, populations, and conclusions between the studies evaluated in this review.
Topics: Humans; Breathing Exercises; Diabetes Mellitus, Type 2; Physical Therapy Modalities; Muscles; Caribbean Region; Muscle Strength; Respiratory Muscles
PubMed: 37403864
DOI: 10.21470/1678-9741-2022-0366 -
International Journal of Molecular... Jul 2023Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer's disease (AD),... (Review)
Review
Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and others. In these diseases, many pathogenic proteins, such as amyloid-β, tau, α-Syn, Htt, and FUS, form aggregates that disrupt the normal physiological function of cells and lead to associated neuronal lesions. Protein aggregates in NDs are widely recognized as one of the important targets for the treatment of these diseases. Natural products, with their diverse biological activities and rich medical history, represent a great treasure trove for the development of therapeutic strategies to combat disease. A number of in vitro and in vivo studies have shown that natural products, by virtue of their complex molecular scaffolds that specifically bind to pathogenic proteins and their aggregates, can inhibit the formation of aggregates, disrupt the structure of aggregates and destabilize them, thereby alleviating conditions associated with NDs. Here, we systematically reviewed studies using natural products to improve disease-related symptoms by reducing or inhibiting the formation of five pathogenic protein aggregates associated with NDs. This information should provide valuable insights into new directions and ideas for the treatment of neurodegenerative diseases.
Topics: Humans; Neurodegenerative Diseases; Protein Aggregates; Biological Products; Parkinson Disease; Alzheimer Disease
PubMed: 37511037
DOI: 10.3390/ijms241411275 -
International Journal of Psychology :... Dec 2023Early-onset depression contributes significantly to the global health burden and has long-term negative effects. This meta-analysis collates and examines the... (Meta-Analysis)
Meta-Analysis Review
Early-onset depression contributes significantly to the global health burden and has long-term negative effects. This meta-analysis collates and examines the effectiveness of family-based interventions, where family members are involved in the treatment of depression in children and adolescents. A literature search was performed up to 8th March 2023. Randomised controlled trials of family-based interventions were included for participants aged 3-18 years with a diagnosis of major depressive disorder or dysthymia, according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) or with a score above a cut-off on a standardised self-report depression measure. The overall effect size for treatment versus active control was g = 0.22 (95% confidence interval [CI]: -0.05-0.50) (nine studies; 659 participants), and for treatment versus non-active control it was g = 0.46 (95% CI: -0.09-1.01) (four studies; 385 participants). Effect sizes were not statistically significant, and heterogeneity was high, ranging between I = 64.3-81.1%. Subgroup analysis comparing attachment-based family therapy with family therapy using other theoretical frameworks did not yield a significant difference between the two. The effects of family-based therapies were larger than those in the comparison groups, but family-based therapy did not demonstrate a significant treatment benefit compared to the controls. More randomised controlled trials are warranted, considering that evidence for other psychotherapies for depression in children and adolescents, indicates modest effects. Family-based therapy may be an alternative for children and adolescents whose needs are not addressed by these treatments.
Topics: Child; Humans; Adolescent; Family Therapy; Depression; Depressive Disorder, Major; Psychotherapy
PubMed: 37409629
DOI: 10.1002/ijop.12926 -
International Journal of General... 2023Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or... (Review)
Review
BACKGROUND
Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or MRI findings are inconsistent or clinical symptoms and imaging findings do not appear simultaneously. We aimed to compile the cases in which imaging findings appeared on MRI retests and to examine in a systematic review whether temporal differences in the appearance of imaging findings correlate with clinical characteristics.
CASE PRESENTATION
An 80-year-old man with type 2 diabetes mellitus came to a hospital with abnormal movements of the left upper and lower extremities. Two days after the first visit, his symptoms flared up, and his head MRI showed an old cerebral infarction and no new lesion. On day 14, he retested T1-weighted imaging and showed a high signal in the right putamen, which was considered diabetic chorea. Blood glucose was controlled with insulin, and the involuntary movements disappeared.
METHODS
PubMed and ICHUSHI were searched to identify patients with diabetic chorea who had undergone MRI retests. Patients grouped by the temporal change in the presence/absence of imaging findings were compared on age, sex, duration of diabetes mellitus, blood glucose level, HbA1c level, side of involuntary movement, time to first MRI, and follow-up MRI.
RESULTS
Of the 64 cases analyzed, 43 (67.2%) were female. The mean age was 69.0 years. 16 (25.0%) had worsening findings upon MRI retesting, 37 (57.8%) had improvement, and 10 (15.6%) had unchanged findings. There were no significant differences in age, sex, mean blood glucose level or HbA1c at onset among the groups.
CONCLUSION
There was no association between the pattern of appearance of imaging findings over time and clinical characteristics, including glucose levels. If initial MRI findings are negative, MRI retesting after a certain time may help diagnose diabetic chorea.
PubMed: 37808208
DOI: 10.2147/IJGM.S423400 -
PloS One 2023Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically...
Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project.
Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.
Topics: Humans; Parkinson Disease; Palliative Care
PubMed: 37788254
DOI: 10.1371/journal.pone.0292180 -
BMJ Mental Health May 2024Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the...
BACKGROUND
Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the literature on HS in patients with neurological disorders. We conducted a systematic review to identify studies that reported HS in neurological disorders. HS was defined as a condition characterized by excessive and persistent preoccupation with sexual thoughts, urges, and behaviors that cause significant distress or impairment in personal, social, or occupational functioning. Data on demographics, assessment techniques, associated elements, phenotypic manifestations, and management strategies were also extracted. The final analysis included 79 studies on HS, encompassing 32 662 patients across 81 cohorts with neurological disorders. Parkinson's disease was the most frequently studied condition (55.6%), followed by various types of dementia (12.7%). Questionnaires were the most common assessment approach for evaluating HS, although the techniques varied substantially. Alterations in the dopaminergic pathways have emerged as contributing mechanisms based on the effects of medication cessation. However, standardized treatment protocols still need to be improved, with significant heterogeneity in documented approaches. Critical deficiencies include risks of selection bias in participant sampling, uncontrolled residual confounding factors, and lack of blinded evaluations of reported outcomes. Despite growth in the last decade, research on HS remains limited across neurological conditions, with lingering quality and methodological standardization deficits. Key priorities include advancing assessment tools, elucidating the underlying neurobiology, and formulating management guidelines.
PROSPERO REGISTRATION NUMBER
CRD42017036478.
Topics: Humans; Nervous System Diseases; Sexual Dysfunctions, Psychological; Male; Female; Parkinson Disease; Sexual Behavior
PubMed: 38777563
DOI: 10.1136/bmjment-2024-300998 -
Journal of Translational Medicine Sep 2023Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.
METHODS
We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.
RESULTS
The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the 'off' state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6-100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the 'off' state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.
CONCLUSIONS
This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760.
Topics: Humans; Parkinson Disease; Levodopa; Transplantation, Autologous; Transplantation, Homologous; Allogeneic Cells
PubMed: 37679754
DOI: 10.1186/s12967-023-04484-x -
International Journal of Molecular... Aug 2023This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has... (Review)
Review
This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has begun to elucidate the multifaceted ways in which HS influences the epigenetic landscape and, subsequently, the progression of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease. HS can modulate key components of the epigenetic machinery, such as DNA methylation, histone modifications, and non-coding RNAs, impacting gene expression and cellular functions relevant to neuronal survival, inflammation, and synaptic plasticity. We synthesize recent research that positions HS as an essential player within this intricate network, with the potential to open new therapeutic avenues for these currently incurable conditions. Despite significant progress, there remains a considerable gap in our understanding of the precise molecular mechanisms and the potential therapeutic implications of modulating HS levels or its downstream targets. We conclude by identifying future directions for research aimed at exploiting the therapeutic potential of HS in neurodegenerative diseases.
Topics: Humans; Hydrogen Sulfide; Epigenesis, Genetic; Neurodegenerative Diseases; Huntington Disease; Cell Survival
PubMed: 37628735
DOI: 10.3390/ijms241612555