搜索结果：Degenerative neurological and neuromuscular disease

Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time. We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution. In 2023, 60·1 million (95% UI 59·0-61·1) deaths occurred globally, of which 4·67 million (4·59-4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2-38·4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8-67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6-51·7) years for females and 47·9 (47·4-48·4) years for males in 1950 to 76·3 (76·2-76·4) years for females and 71·4 (71·3-71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6-74·8) years for females and 69·3 (69·2-69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0-76·6] years for females and 71·5 [71·2-71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally. This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world. Gates Foundation.

Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Gates Foundation.

Spermidine is a naturally occurring polyamine involved in multiple cellular processes, including growth regulation, protein translation, and autophagy. Increasing attention has been devoted to its potential neuroprotective effects, particularly in Alzheimer's disease (AD), a neurodegenerative disorder characterized by β-amyloid and phosphorylated tau accumulation, synaptic dysfunction, and progressive neuronal loss. In this narrative review, we examine potential mechanisms through which spermidine may influence AD pathophysiology and summarize available preclinical and clinical evidence. Preclinical studies indicate that spermidine induces autophagy, a key cellular clearance pathway responsible for removing damaged organelles and aggregated proteins. Because impaired neuronal autophagy contributes to the accumulation of β-amyloid and tau in AD, increasing intracellular spermidine levels may enhance the degradation of these toxic species. In addition, spermidine exhibits anti-inflammatory and antioxidant properties, attenuates microglial activation, and supports mitochondrial function. In animal models of AD and brain aging, spermidine administration has been associated with improvements in cognitive performance and synaptic function. However, human clinical evidence remains limited and largely inconclusive. Observational studies suggest associations between higher dietary spermidine intake and better cognitive outcomes, but do not establish causality. Randomized clinical trials to date are few, include small and heterogeneous populations, and have not demonstrated consistent effects on primary cognitive endpoints. Overall, spermidine represents a biologically plausible modulator of pathways relevant to neurodegeneration, but translation of preclinical findings into clinical benefit remains uncertain. Current evidence is insufficient to support its use as a therapeutic or preventive intervention in AD, and further well-designed clinical studies are required to clarify its efficacy and mechanisms of action. Alzheimer’s disease is one of the most common causes of memory loss in older adults. Researchers are searching for ways to protect brain cells and slow the biological processes that lead to this disease. One molecule that has recently attracted attention is spermidine, a natural compound found in all living cells and in many foods, including whole grains, legumes, mushrooms, and aged cheeses. Spermidine plays several roles in the body. One of its most important effects is activation of autophagy, a natural cellular process that removes damaged proteins and other cellular waste. This process is relevant to Alzheimer’s disease because the condition is associated with the accumulation of abnormal proteins in the brain. Experimental studies also suggest that spermidine may influence inflammation in the brain, support mitochondrial function (the energy system of cells), and help maintain communication between nerve cells. In this review, we summarized evidence from laboratory experiments, animal studies, and available human research. In animal models of brain aging and Alzheimer’s disease, spermidine consistently shows neuroprotective effects and can improve memory performance. Human evidence is more limited. Observational studies suggest that higher dietary spermidine intake may be associated with better cognitive performance, while clinical trials investigating supplementation have produced mixed results. Spermidine is naturally present in many foods and is increasingly studied in the context of aging and brain health. Overall, current evidence suggests that spermidine may play a role in brain aging. Larger and well-designed clinical studies are needed to clarify its potential relevance for Alzheimer’s disease.

Multiple sclerosis (MS) is a neurological disorder affecting almost 2.8 million people globally, approximately 80-85% of whom have the relapsing-remitting form of the disease (RRMS). There are several autoinjectors available for the administration of injectable disease-modifying therapies for the treatment of MS. The objective of the current study was to gain an understanding of factors related to patients' and nurses' autoinjector preferences, and to evaluate two autoinjectors for glatiramer acetate (MyJECT™ and CSYNC™) against those preferences. Patients with RRMS and nurses experienced in training patients with an autoinjector were recruited from 12 health centers in Germany. Surveys were administered to patients and nurses and their answers to 13 questions over five categories (participants' characteristics, important autoinjector attributes, autoinjector performance, satisfaction with the autoinjector devices and demographics) were scored, where appropriate, using a 5-point Likert scale. A total of 15 patients and 15 nurses were included in the study. Overall, the top four most important attributes, for both nurses and patients, were ease of handling, ability to use independently, ease of gripping the autoinjector and ease of self-injection. MyJECT™ received a mean score of at least 4.5 (out of 5) on more attributes than CSYNC™ and satisfaction with both autoinjectors was high. Nurses and patients with RRMS were highly satisfied with both the MyJECT™ and CSYNC™ autoinjectors, with scores suggesting that MyJECT™ performs better on the attributes they identified as most important. All patients currently using the MyJECT™ were likely or highly likely to recommend it to another patient with RRMS. Multiple sclerosis is a disorder of the brain and spinal cord that affects almost 3 million people worldwide. Some of the multiple sclerosis treatments may need patients to inject the medicine at regular intervals. There are several different injection devices to administer the drugs for the management of multiple sclerosis, these are called autoinjectors. MyJECT™ and CSYNC™ are two different autoinjectors that patients can use with a drug called glatiramer acetate. The current study was done to look at what features of autoinjectors do patients and nurses think are most important. To do this, a survey was completed among “multiple sclerosis nurses” and “patients with a type of multiple sclerosis called relapsing-remitting multiple sclerosis” who visited one of 12 health centers in Germany. The survey had 13 questions covering patient background, important features of autoinjectors, autoinjector performance, satisfaction with the autoinjector, and patient demographics (age, gender and education). Overall, 15 nurses and 15 patients took part. Both nurses and patients answered that the top four features of autoinjectors were ease of handling, ability to use independently, ease of gripping the autoinjector and ease of self-injection. The MyJECT™ autoinjector was given an average score of at least 4.5 out of 5 more often than the CSYNC™ autoinjector, although patients and nurses had high levels of satisfaction with both types of autoinjector. The overall conclusion was that multiple sclerosis nurses and patients were highly satisfied with both the MyJECT™ and CSYNC™ autoinjectors, with higher scores for MyJECT™ for features considered to be most important. All patients currently using MyJECT™ were likely to recommend it to another patient with relapsing-remitting multiple sclerosis.

Parkinson's disease (PD) is the fastest growing progressive neurological disorder globally, characterized by motor symptoms such as bradykinesia, rigidity, resting tremor as well as a wide range of non-motor manifestations. Here, we report the case of a patient with advanced Parkinson's disease diagnosed for PD more than 12 years ago; clinical symptoms included a coarse resting tremor with a focus on the right arm and leg, gait and postural disturbances, sleep disorders and autonomic disfunctions. The patient received several medications for correction of dopamine deficiency, but clinical symptoms progressed over the years. We applied a series of double-filtration apheresis treatments and experienced marked symptomatic improvement, with near-complete resolution of motor deficits and strong decrease of MDS-UPDRS part III score. This case suggests a potential role of extracorporeal blood purification in the management of PD. Parkinson’s disease is a long-term brain disorder that gradually worsens over time. It affects movement, causing symptoms such as slowness, stiffness, and shaking, and can also lead to problems with sleep, sense of smell, balance, and automatic body functions. Current treatments mainly aim to replace dopamine, but do not stop disease progression. This report describes a patient who had Parkinson’s disease for more than 12 years whose condition continued to worsen despite standard therapy. The patient had severe tremor, impaired walking and posture, sleep disturbances, loss of smell and autonomic symptoms. A special blood-cleaning treatment called double-filtration apheresis was used. This treatment filters the blood to remove certain harmful substances of larger mass as, for example, immune complexes, autoantibodies or substances that trigger inflammation, before returning it to the body. After a series of treatments, the patient showed marked improvement, with most movement problems almost completely disappearing and restoration of sense of smell and sleep. The improvement of symptoms was also reflected in improved laboratory results. This is a single case, so firm conclusions cannot be drawn and further clinical studies are needed. Overall, therapeutic apheresis may represent a promising additional treatment option for patients with advanced Parkinson’s disease who do not respond well to standard therapies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.

The dramatic surge of neurodegenerative disorders among elderly population underscore the pressing demand for development of optimal and evidence based noninvasive natural treatment strategies. Paraquat exposure in animal models used in scientific studies can cause a variety of clinical signs of Parkinson disease (PD). The health benefits of thyme include antioxidant, anti-inflammatory, pulmonary, and neurological benefits. Thyme and other herbal treatments are frequently used to treat a variety of conditions, including neurological issues. The primary factor in the etiology of neurodegeneration is oxidative stress. Conventional treatments are indicated to potentially have negative side effects. The primary phytochemicals of Thymus vulgaris (TV), which are responsible for its unique therapeutic property of neuro-protection, include hydrocarbon and phenolic compounds like thymol and carvacrol. The goal of the current investigation was to examine T. vulgaris' potential for neuroprotection while also ensuring its safety. Analyses of the plant's physicochemical and phytochemical composition were performed by liquid chromatographic analysis. Neuro-behavioral and biochemical parameters were evaluated to determine the impact of T. vulgaris in paraquat induced parkinsonian rodents model. The neurobehavioral tests include open field tests for movement and exploration, Y maze test and elevated plus maze test for natural behavior, memory, and anxiety, hole board tests for exploratory behavior, ladder climbing, foot printing, and wire hanging tests for estimating neuromuscular coordination. T. vulgaris treatment significantly improved neurobehavioral parameters dose-dependently, Biochemical analysis revealed that extract treatment mitigated the declined level of antioxidant enzymes. RT-PCR analysis showed that in paraquat treated group mRNA expression of IL-1α, IL-1β, Alpha-Synuclein, TNF-α, and IL-6 was upregulated markedly. However, T. vulgaris treatment dose dependently down-regulated the mRNA expression of these genes. The groundbreaking results of current study revealed that T. vulgaris restored the degenerative alterations, neuro-inflammation, and nerve loss in the brain structure, as evident by histopathological investigation. Particularly remarkable restoration in neuropsychological and biochemical markers emphasize the medicinal potential of T. vulgaris as a revolutionary treatment for neurodegenerative disorders, offering new hope for millions worldwide afflicted by these devastating conditions.

Conventional therapeutic interventions for Alzheimer's disease (AD) are limited by multiple drawbacks, including anticholinesterase inhibitors, glutamate receptor antagonists, intestinal flora regulators and Aβ-targeting monoclonal antibodies, which only achieve modest symptomatic relief, are accompanied by notable adverse events (e.g., intracerebral hemorrhage, cerebral edema) and have suboptimal clinical efficacy. In recent years, the cerebral lymphatic system, consisting of the glial lymphatic system (GLS) and meningeal lymphatic vessels (MLVs), has been identified as a key mediator of amyloid β-protein (Aβ) clearance and a critical driver of AD pathogenesis. Lymphatic dysfunction in this system precedes and exacerbates Aβ deposition and cognitive decline in AD patients, revealing the close association between cerebral lymphatic system impairment and AD progression. This study aims to focus on the emerging therapeutic advancements for AD targeting the cerebral lymphatic system, moving beyond the conventional symptomatic treatments and Aβ-centric interventions. It also intends to systematically summarize the relevant mechanisms of the cerebral lymphatic system in AD and the diverse therapeutic strategies targeting this system, thus providing a framework for developing innovative clinical interventions for AD. This study adopted a review approach, systematically collating and analyzing existing research on the cerebral lymphatic system and AD, including the cerebral lymphatic pathway of Aβ clearance, the pathological consequences of lymphatic impairment in AD, and various therapeutic strategies targeting the cerebral lymphatic system that have been reported in current studies. The review identified and summarized multiple categories of effective therapeutic strategies targeting the cerebral lymphatic system for AD, covering pharmacological agents (VEGF-C, traditional Chinese medicines, oxytocin), photobiotherapies (808 nm near-infrared light, 40 Hz multisensory stimulation), physiotherapies (aerobic exercise, rTMS), gene therapy (DSCR1 upregulation), and surgical interventions (lymphatic-venous anastomosis). All these strategies are designed to optimize cerebral lymphatic function and thereby enhance Aβ drainage in the brain. Optimizing cerebral lymphatic function to enhance Aβ drainage is a viable, disease-modifying therapeutic direction for AD. This therapeutic approach targeting the cerebral lymphatic system can serve as a complementary or alternative method to current symptomatic or Aβ-targeted treatments for AD, and also provides a theoretical and practical framework for the development of innovative clinical interventions for the disease.

Multisystem proteinopathy (MSP) is a pleiotropic group of disorders initially presenting as inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and/or Paget disease of bone (PDB). Additional genes including MATR3, OPTN, and ANXA11, have recently been implicated in MSP-like disorders, further expanding the genetic spectrum. This research aims to study the genetic and clinical characteristics of MSP and related disorders in a large Chinese cohort. Twenty-nine patients were identified in 953 patients diagnosed with ALS, IBM, or dementia at Huashan Hospital between 2000 and 2024. Variants in MSP-related genes were detected using next-generation sequencing and confirmed by Sanger sequencing. Clinical, pathological, imaging, and electromyography data were collected and analyzed. A total of 29 patients (3.0%) were identified as carrying MSP-related gene variants. Most patients were male (72.4%), with disease onset predominantly in the third to fifth decades of life. The majority of patients (21/29) presented with a single clinical phenotype. ALS was the most common phenotype (20/29), followed by IBM (10/29), FTD (7/29), and PDB (1/29). The most frequent variants were in ANXA11 (34.5%) and VCP (20.7%), followed by OPTN (17.2%), SQSTM1 (10.3%), MATR3 (10.3%), and HNRNPA1 (6.9%). All patients with VCP variants presented with initial lower limb involvement, whereas those carrying ANXA11 or OPTN variants predominantly showed upper limb or bulbar onset. Patients harboring OPTN variants had a later age at onset compared with those carrying VCP or MATR3 variants. Patients with ALS-onset exhibited faster progression compared with those with myopathy-onset, even when harboring identical variants. This study broadens the clinical and genetic landscape of MSP and related disorders in a Chinese cohort. These results emphasize the clinical utility of next-generation sequencing for improving diagnostic accuracy in patients with unexplained neuromuscular or cognitive presentations, especially in the presence of multisystem involvement.

The symptoms of patients with early to mid-stage Parkinson's disease (PD) are closely associated with their quality of life. However, few studies have explored the relationship between symptoms and quality of life. This study aims to investigate the symptom profiles of patients with early to mid-stage PD, construct a symptom network to identify core symptoms, and examine their associations with quality of life. This cross-sectional study was conducted from November 2024 to February 2025 among 954 patients with early to mid-stage PD in China, with stages 1-2 classified as early stage and stage 3 as mid stage. All participants completed the PD Symptom Experience Scale. Network models were constructed using R version 4.4.3 to identify core symptoms, describe inter-symptom relationships, and calculate centrality indices. The top three symptoms in terms of prevalence were bradykinesia (77.46%), resting tremor (75.05%), and rigidity (59.01%). The most severe symptom was resting tremor. In the symptom network analysis, the top three symptoms with the highest node centrality were bradykinesia (re=1.27), postural instability (re=1.16), and limb stiffness (re=1.96). In the quality of life network, the dimensions with the highest node centrality were "mobility" (rbe=0.52), "emotional well-being" (rbe=0.50), and "cognitions" (rbe=0.49). "Mobility" was positively correlated with difficulty turning over in bed (r=0.19), freezing of gait (r=0.09), and difficulty standing up or sitting down (r=0.08). Multiple symptoms were simultaneously experienced by patients with early to mid-stage PD, and interrelationships among symptoms were observed. Bradykinesia was identified as the core symptom, and the "mobility" dimension was recognized as the central node in the quality of life network. Healthcare providers are advised to comprehensively consider patients' overall symptom profiles and their relationships with quality of life, and to implement targeted, integrated interventions.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aβ) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aβ oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagnosis. The advent of ultra-sensitive detection methodologies, including single-molecule enzyme-linked immunosorbent assay and immunoprecipitation-mass spectrometry, has revolutionized the detection of AD plasma biomarkers, supplanting previous low-sensitivity techniques. This rapid advancement in detection technology facilitates the more accurate quantification of pathological brain proteins and AD-associated biomarkers in the bloodstream. This manuscript meticulously reviews the landscape of current research on immunological markers for AD, anchored in the National Institute on Aging-Alzheimer's Association AT(N) research framework. It highlights a selection of forefront ultra-sensitive detection technologies now integral to assessing AD blood immunological markers. Additionally, this review examines the crucial pre-analytical processing steps for AD blood samples that significantly impact research outcomes and addresses the practical challenges faced during clinical testing. These discussions are crucial for enhancing our comprehension and refining the diagnostic precision of AD using blood-based biomarkers. The review aims to shed light on potential avenues for innovation and improvement in the techniques employed for detecting and investigating AD, thereby contributing to the broader field of neurodegenerative disease research.

Dementia diagnosis in sub-Saharan Africa is constrained by limited access to specialist neuroimaging interpretation and reduced specificity of brief cognitive tools in low-literacy populations. We evaluated the agreement, incremental value, and comparative performance of Mini Mental State Exam (MMSE), visual MRI medial temporal atrophy (MTA), and automated brain morphometry in older Ugandan adults with suspected dementia. In this cross-sectional study, adults aged &#x2265;50 years with suspected dementia were recruited from neurology and psychiatry clinics at two hospitals and from a community cohort. Participants underwent MMSE and standardized 1.5T brain MRI. Visual MRI ratings were performed by radiologists blinded to clinical data, and automated morphometry was generated using NeuroQuant&#xae; normative percentiles. Hippocampal occupancy (HOC <5th percentile) was used as a reference MRI biomarker for comparative classification. Agreement between visual and automated measures was assessed using Spearman correlation and intraclass correlation. Incremental value was assessed using regression models, and comparative performance using area under the curve (AUC). Sixty-three participants were included (mean age 75.6 &#xb1; 8.7 years; 49 female). Agreement between visual ratings and automated morphometry was poor. MMSE correlated inversely with MTA (&#x3c1; = -0.47; p = 0.049) and correlated positively with hippocampal volume percentile (&#x3c1; = 0.46; p = 0.056). Adding hippocampal volume to MTA did not improve model fit for MMSE (&#x394;R2 = 0.028; p = 0.18). For comparative classification, MMSE alone was sensitive but poorly specific, while the combined MMSE-MTA model improved specificity and discrimination (AUC 0.70 vs 0.62 for either measure alone). Visual and automated MRI measures were not interchangeable in this heterogeneous cohort. Automated hippocampal volumetry added limited value beyond visual MTA for global cognition, while combining MMSE with visual MTA showed modest improvement in comparative classification and warrants further validation.

To report the clinical and genetic characteristics of a rare Charcot-Marie-Tooth disease type 2F (CMT2F) pedigree, and to explore the phenotypic diversity and diagnostic essentials of the mutation in combination with literature review. The clinical data, electrophysiological findings, and genetic testing results of the proband and pedigree members were retrospectively analyzed, and relevant literatures were reviewed for comparative analysis. Both patients had an onset in middle and old age (50/66 years), presenting with distal lower limb muscle weakness (Grade III), muscle atrophy, absent tendon reflexes, pes cavus, and sensory abnormalities. Serum creatine kinase (CK) was elevated (474 U/L), and electromyography indicated axonal peripheral nerve damage. Genetic testing revealed a heterozygous mutation of HSPB1 gene c.418C>G [p.Arg140Gly], which was verified by co-segregation in the pedigree. Literature review showed that this mutation causes axonal transport dysfunction by impairing the chaperone function of HSP27. This study expands the phenotypic spectrum of late-onset CMT2F, with some patients showing mild elevation of serum CK. It provides new clinical evidence for the pathogenicity of this mutation.

To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer's disease (AD) based on the expression of miRNAs in AD patients. We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1-67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways.

Apoptosis and immune inflammation play important roles in the pathological process of Alzheimer's disease (AD), but their specific pathogenesis is still unclear. Therefore, this article focuses on exploring the effects of Danzhi Xiaoyao Powder (DXP) on the learning and memory ability of AD model rats from the dual mechanisms of apoptosis and immune inflammation. The AD model was replicated by injecting Okadaic acid (100 ng) into the bilateral hippocampus of rats. Successful rats were selected and orally administered with donepezil hydrochloride and DXP decoction for 42 days. Their learning and memory abilities, hippocampal morphology, A&#x3b2; expression, inflammatory factors, apoptotic factors, anti apoptotic factors, as well as the expression of pathway proteins and mRNA were detected. After DXP intervention, the learning and memory abilities of rats improved, the neuronal cell arrangement was more complete, the expression of A&#x3b2; decreased, the expression of pro-inflammatory cytokine and apoptotic factors decreased, the expression of anti apoptotic factors increased, Protein Kinase B (Akt) expression and activity significant up-regulation, and nuclear factor kappa-B (NF-&#x3ba;B), p38 MAPK (p38), MAPKAPK-2 (MK2), Cyclooxygenase-2 (COX-2) protein and mRNA expression were significantly down-regulated. DXP can improve the learning and cognitive abilities of AD model rats, and its mechanism of action may be related to the regulation of the Akt/NF-&#x3ba;B apoptosis pathway mediated by NF-&#x3ba;B interaction and the p38MAPK/MK2/COX-2 immune inflammatory dual pathway.

X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India. We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD. ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.

Exploring the effects of acupuncture at the "Yizhi Tiaoshen" acupoint on blood oxygen metabolism and neurological function changes in the brain regions of AD model rats. The AD model was replicated by intraperitoneal injection of D-galactose combined with bilateral hippocampal CA1 injection of Okadaic acid (OA). Thirty rats with successfully replicated model were selected through Morris water maze experiment and randomly divided into model group, donepezil hydrochloride group, and acupuncture group, with 10 rats in each group. After treatment, fNIRs were used to detect changes in Oxy Hb, Deoxy Hb, and Total Hb in the cerebral cortex of rats in each group, in order to evaluate the neurological function changes in key brain areas. The escape latency of the donepezil hydrochloride group and the acupuncture group was shortened, the number of crossings through the original platform increased, and the duration of stay in the quadrant where the original platform was located was prolonged. Based on fNIRs detection, the main differential channels of blood oxygen metabolism in AD rats were identified as 2-2 and 8-7, corresponding to the prefrontal and parietal lobes, respectively. The concentrations of Oxy Hb and Total Hb were significantly increased in both treatment groups, while the concentration of Deoxy Hb was significantly decreased. Acupuncture with the "Yizhi Tiaoshen" acupoint formula and donepezil hydrochloride can improve the learning and memory function of AD rats, and its mechanism may be related to improving blood oxygen metabolism in the prefrontal and parietal regions and protecting neuronal function.

Parkinson's disease is a neurodegenerative disorder that leads to neuronal loss. Though a variety of genetic and environmental factors may be involved in the etiology, the presentation of the disorder is very similar. Trace minerals such as manganese are essential for brain development and function though effective concentrations are paramount. Exposure to high concentrations of manganese is known to cause neurotoxicity and has been recently associated with manganese-induced parkinsonism, which will be explored in this review. This review synthesizes findings from peer-reviewed clinical, epidemiological, and experimental studies to explore the underlying mechanisms and contributing factors of manganese-induced parkinsonism. Specifically, it examines alterations in lipidomic and oxidative profiles, enhancement of redox cycling, transporter dysfunction and deficiency, ion homeostasis, dysregulation of signaling pathways and autophagy, mRNA disruption, dopamine toxicity, manganese contamination, and neuroprotective mechanisms. Preventative and therapeutic interventions-including chelation therapy with ethylene-diamine-tetra-acetic acid (CaNa2EDTA), with or without plasma exchange and para-aminosalicylic acid (PAS), as well as natural compounds such as vinpocetine (VIN), punicalagin (PUN), niacin, vitamin E, DNLA, curcumin, and sesame oil-are also reviewed. Given manganese's role as an oxidant in the synthesis of neurotoxic compounds, therapeutic strategies targeting both manganese, its associated molecular pathways, and its downstream neurotoxic effects may represent the most promising direction for future research.