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Pharmaceuticals (Basel, Switzerland) May 2024Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing... (Review)
Review
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.
PubMed: 38794180
DOI: 10.3390/ph17050610 -
Life (Basel, Switzerland) May 2024Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain... (Review)
Review
Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain primary, increasing evidence supports the role of non-pharmacological strategies like physical activity in managing these conditions. This systematic review critically evaluates the effectiveness of Nursing based physical activity interventions in improving cognitive function, physical functioning, mobility, and overall quality of life among older adults with neurodegenerative diseases. We conducted a comprehensive search across PubMed, EMBASE, Web of Science, CENTRAL, and other relevant databases, focusing on randomized controlled trials and observational studies that examined the impact of structured physical activity. Our findings from nineteen studies involving 1673 participants indicate that interventions ranging from aerobic exercises, resistance training, to mind-body exercises like Tai Chi and yoga have beneficial effects. Specifically, physical activity was consistently found to enhance cognitive performance, increase mobility, and improve balance and daily living activities, contributing to a better quality of life. However, these benefits vary depending on the type, intensity, and duration of the activity performed. Despite promising results, limitations such as small sample sizes, study heterogeneity, and short-term follow-up periods call for more robust, long-term studies to solidify these findings. This review underscores the potential of tailored physical activity programs as adjunctive therapy in the comprehensive management of neurodegenerative diseases among the elderly population.
PubMed: 38792618
DOI: 10.3390/life14050597 -
International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198 -
Brain Sciences May 2024People with Parkinson's disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that... (Review)
Review
BACKGROUND
People with Parkinson's disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that dual-task gait training improves spatiotemporal gait parameters, it remains unclear whether dual-task gait training specifically improves dual-task gait performance compared to single-task gait training. The aim of this review is to assess the effect of dual-task training relative to single-task gait training on specific gait parameters during dual-task tests in pwPD.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), searching three electronic databases. Two reviewers independently selected RCTs, extracted data, and applied the Cochrane risk-of-bias tool for randomized trials (Version 2) and the GRADE framework for assessing the certainty of evidence. The primary outcomes were dual-task gait speed, stride length, and cadence. Secondary outcomes included dual-task costs on gait speed, balance confidence, and quality of life.
RESULTS
We included 14 RCTs (548 patients). Meta-analyses showed effects favoring dual-task training over single-task training in improving dual-task gait speed (standardized mean difference [SMD] = 0.48, 95% confidence interval [CI] = 0.20-0.77; 11 studies; low certainty evidence), stride length (mean difference [MD] = 0.09 m, 95% CI = 0.04-0.14; 4 studies; very low certainty evidence), and cadence (MD = 5.45 steps/min, 95% CI = 3.59-7.31; 5 studies; very low certainty evidence). We also found a significant effect of dual-task training over single-task training on dual-task cost and quality of life, but not on balance confidence.
CONCLUSIONS
Our findings support the use of dual-task training relative to single-task training to improve dual-task spatiotemporal gait parameters in pwPD. Further studies are encouraged to better define the features of dual-task training and the clinical characteristics of pwPD to identify better responders.
PubMed: 38790495
DOI: 10.3390/brainsci14050517 -
Ageing Research Reviews Jul 2024We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive.
METHODS
We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses.
RESULTS
We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 - 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 - 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 - 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 - 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 - 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 - 1.27). The effect of hearing loss did not vary across potential moderators.
CONCLUSIONS
Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.
Topics: Aged; Humans; Age of Onset; Cognitive Dysfunction; Cohort Studies; Dementia; Hearing Loss; Incidence; Risk Factors
PubMed: 38788800
DOI: 10.1016/j.arr.2024.102346 -
Frontiers in Aging Neuroscience 2024Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the...
Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD.
PubMed: 38784446
DOI: 10.3389/fnagi.2024.1382593 -
Cureus Apr 2024Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, poses a significant healthcare challenge worldwide. The accumulation of... (Review)
Review
Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, poses a significant healthcare challenge worldwide. The accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein drives neuronal degeneration and neuroinflammation, perpetuating disease progression. Despite advancements in understanding the cellular and molecular mechanisms, treatment hurdles persist, emphasizing the need for innovative intervention strategies. Quantum dots (QDs) emerge as promising nanotechnological tools with unique photo-physical properties, offering advantages over conventional imaging modalities. This systematic review endeavors to elucidate the theranostic potential of QDs in AD by synthesizing preclinical and clinical evidence. A comprehensive search across electronic databases yielded 20 eligible studies investigating the diagnostic, therapeutic, or combined theranostic applications of various QDs in AD. The findings unveil the diverse roles of QDs, including inhibiting Aβ and tau aggregation, modulating amyloidogenesis pathways, restoring membrane fluidity, and enabling simultaneous detection of AD biomarkers. The review highlights the potential of QDs in targeting multiple pathological hallmarks, delivering therapeutic payloads across the blood-brain barrier, and facilitating real-time imaging and high-throughput screening. While promising, challenges such as biocompatibility, surface modifications, and clinical translation warrant further investigation. This systematic review provides a comprehensive synthesis of the theranostic potential of QDs in AD, paving the way for translational research and clinical implementation.
PubMed: 38770476
DOI: 10.7759/cureus.58677 -
Respiratory Medicine Jul 2024Sex and gender are related concepts, but they have distinct meanings and implications. Respiratory diseases are a major driver of morbi-mortality. It is frequent that... (Review)
Review
CONTEXT
Sex and gender are related concepts, but they have distinct meanings and implications. Respiratory diseases are a major driver of morbi-mortality. It is frequent that respirologists, primary care doctors, or other specialists, when dealing with respiratory patients, and aiming for a holistic management of their patients, they all skip any question or matter associated with sexual activity or behavior.
OBJECTIVES
To review how sexual activity is explored in respiratory patients.
METHODS
To conduct this review, we endorse PRISMA guidance for reporting systematic reviews, and also the sex and gender equity in research (SAGER) guidelines.
RESULTS
Compared to other conditions such as heart disease, mental disorders, Alzheimer's, or even COVID-19, to date there is no review focused on sexual activity and respiratory health and disease. Asthma, COPD and other respiratory patients can have their sexual activity and behaviors affected by their disease, but also limitations in sex might be the sentinel event of an incident respiratory disease. Asking on sexual desire and related sex issues should not be considered taboo in any respiratory consultation. Importantly, any marketed stereotypes on cigarettes after any sexual activity should be counteracted. Many clinical trials of respiratory drugs keep recruiting few or no women, so research on women's sexual desire and satisfaction lags behind that of men's. By using the available objective tools and validated questionnaires summarized in this review, these important domains of respiratory patients and their partners can be properly identified and managed.
CONCLUSIONS
Sexual activity, depending on age and individual specific conditions, is a fundamental driver of overall health, and therefore of lung health.
Topics: Humans; Sexual Behavior; Female; Male; Asthma; Pulmonary Disease, Chronic Obstructive; COVID-19; Sex Factors; Respiratory Tract Diseases
PubMed: 38768665
DOI: 10.1016/j.rmed.2024.107665 -
Frontiers in Aging Neuroscience 2024Mild cognitive impairment (MCI) is commonly defined as a transitional subclinical state between normal aging and dementia. A growing body of research indicates that...
BACKGROUND
Mild cognitive impairment (MCI) is commonly defined as a transitional subclinical state between normal aging and dementia. A growing body of research indicates that health behaviors may play a protective role against cognitive decline and could potentially slow down the progression from MCI to dementia. The aim of this study is to conduct a bibliometric analysis of literature focusing on health behaviors and MCI to summarize the factors and evidence regarding the influence of health behaviors on MCI.
METHODS
The study performed a bibliometric analysis by retrieving publications from the Science Citation Index and Social Sciences Citation Index sub-databases within the Web of Science Core Collection. Utilizing VOSviewer and CiteSpace software, a total of 2,843 eligible articles underwent co-citation, co-keywords, and clustering analyses. This methodology aimed to investigate the current status, trends, major research questions, and potential future directions within the research domain.
RESULTS
The bibliometric analysis indicates that research on healthy behaviors in individuals with MCI originated in 2002 and experienced rapid growth in 2014, reflecting the increasing global interest in this area. The United States emerged as the primary contributor, accounting for more than one-third of the total scientific output with 982 articles. Journals that published the most articles on MCI-related health behaviors included "Journal of Alzheimer's Disease," "Neurobiology of Aging," "Frontiers in Aging Neuroscience," and other geriatrics-related journals. High-impact papers identified by VOSviewer predominantly cover concepts related to MCI, such as diagnostic criteria, assessment, and multifactorial interventions. Co-occurrence keyword analysis highlights five research hotspots in health behavior associated with MCI: exercise, diet, risk factors and preventive measures for dementia, cognitive decline-related biomarkers, and clinical trials.
CONCLUSION
This study provides a comprehensive review of literature on health behavior in individuals with MCI, emphasizing influential documents and journals. It outlines research trends and key focal points, offering valuable insights for researchers to comprehend significant contributions and steer future studies.
PubMed: 38765772
DOI: 10.3389/fnagi.2024.1402347 -
The Cochrane Database of Systematic... May 2024Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and well-being). Interventions that aim to prevent obesity involve behavioural change strategies that promote healthy eating or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective and numerous new studies have been published over the last five years, since the previous version of this Cochrane review.
OBJECTIVES
To assess the effects of interventions that aim to prevent obesity in children by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was February 2023.
SELECTION CRITERIA
Randomised controlled trials in children (mean age 5 years and above but less than 12 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our outcomes were body mass index (BMI), zBMI score and serious adverse events, assessed at short- (12 weeks to < 9 months from baseline), medium- (9 months to < 15 months) and long-term (≥ 15 months) follow-up. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
This review includes 172 studies (189,707 participants); 149 studies (160,267 participants) were included in meta-analyses. One hundred forty-six studies were based in high-income countries. The main setting for intervention delivery was schools (111 studies), followed by the community (15 studies), the home (eight studies) and a clinical setting (seven studies); one intervention was conducted by telehealth and 31 studies were conducted in more than one setting. Eighty-six interventions were implemented for less than nine months; the shortest was conducted over one visit and the longest over four years. Non-industry funding was declared by 132 studies; 24 studies were funded in part or wholly by industry. Dietary interventions versus control Dietary interventions, compared with control, may have little to no effect on BMI at short-term follow-up (mean difference (MD) 0, 95% confidence interval (CI) -0.10 to 0.10; 5 studies, 2107 participants; low-certainty evidence) and at medium-term follow-up (MD -0.01, 95% CI -0.15 to 0.12; 9 studies, 6815 participants; low-certainty evidence) or zBMI at long-term follow-up (MD -0.05, 95% CI -0.10 to 0.01; 7 studies, 5285 participants; low-certainty evidence). Dietary interventions, compared with control, probably have little to no effect on BMI at long-term follow-up (MD -0.17, 95% CI -0.48 to 0.13; 2 studies, 945 participants; moderate-certainty evidence) and zBMI at short- or medium-term follow-up (MD -0.06, 95% CI -0.13 to 0.01; 8 studies, 3695 participants; MD -0.04, 95% CI -0.10 to 0.02; 9 studies, 7048 participants; moderate-certainty evidence). Five studies (1913 participants; very low-certainty evidence) reported data on serious adverse events: one reported serious adverse events (e.g. allergy, behavioural problems and abdominal discomfort) that may have occurred as a result of the intervention; four reported no effect. Activity interventions versus control Activity interventions, compared with control, may have little to no effect on BMI and zBMI at short-term or long-term follow-up (BMI short-term: MD -0.02, 95% CI -0.17 to 0.13; 14 studies, 4069 participants; zBMI short-term: MD -0.02, 95% CI -0.07 to 0.02; 6 studies, 3580 participants; low-certainty evidence; BMI long-term: MD -0.07, 95% CI -0.24 to 0.10; 8 studies, 8302 participants; zBMI long-term: MD -0.02, 95% CI -0.09 to 0.04; 6 studies, 6940 participants; low-certainty evidence). Activity interventions likely result in a slight reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.18 to -0.05; 16 studies, 21,286 participants; zBMI: MD -0.05, 95% CI -0.09 to -0.02; 13 studies, 20,600 participants; moderate-certainty evidence). Eleven studies (21,278 participants; low-certainty evidence) reported data on serious adverse events; one study reported two minor ankle sprains and one study reported the incident rate of adverse events (e.g. musculoskeletal injuries) that may have occurred as a result of the intervention; nine studies reported no effect. Dietary and activity interventions versus control Dietary and activity interventions, compared with control, may result in a slight reduction in BMI and zBMI at short-term follow-up (BMI: MD -0.11, 95% CI -0.21 to -0.01; 27 studies, 16,066 participants; zBMI: MD -0.03, 95% CI -0.06 to 0.00; 26 studies, 12,784 participants; low-certainty evidence) and likely result in a reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.21 to 0.00; 21 studies, 17,547 participants; zBMI: MD -0.05, 95% CI -0.07 to -0.02; 24 studies, 20,998 participants; moderate-certainty evidence). Dietary and activity interventions compared with control may result in little to no difference in BMI and zBMI at long-term follow-up (BMI: MD 0.03, 95% CI -0.11 to 0.16; 16 studies, 22,098 participants; zBMI: MD -0.02, 95% CI -0.06 to 0.01; 22 studies, 23,594 participants; low-certainty evidence). Nineteen studies (27,882 participants; low-certainty evidence) reported data on serious adverse events: four studies reported occurrence of serious adverse events (e.g. injuries, low levels of extreme dieting behaviour); 15 studies reported no effect. Heterogeneity was apparent in the results for all outcomes at the three follow-up times, which could not be explained by the main setting of the interventions (school, home, school and home, other), country income status (high-income versus non-high-income), participants' socioeconomic status (low versus mixed) and duration of the intervention. Most studies excluded children with a mental or physical disability.
AUTHORS' CONCLUSIONS
The body of evidence in this review demonstrates that a range of school-based 'activity' interventions, alone or in combination with dietary interventions, may have a modest beneficial effect on obesity in childhood at short- and medium-term, but not at long-term follow-up. Dietary interventions alone may result in little to no difference. Limited evidence of low quality was identified on the effect of dietary and/or activity interventions on severe adverse events and health inequalities; exploratory analyses of these data suggest no meaningful impact. We identified a dearth of evidence for home and community-based settings (e.g. delivered through local youth groups), for children living with disabilities and indicators of health inequities.
Topics: Child; Child, Preschool; Female; Humans; Male; Bias; Body Mass Index; Diet, Healthy; Energy Intake; Exercise; Pediatric Obesity; Randomized Controlled Trials as Topic; Sedentary Behavior; Sleep
PubMed: 38763517
DOI: 10.1002/14651858.CD015328.pub2