Neurodegenerative disease management最新文献

Background: Despite emerging therapeutic options, Alzheimer´s disease (AD) management remains suboptimal due to multimodal pathogenesis. We investigated curcumin-donepezil combination therapy, as curcumin demonstrates antioxidant, anti-inflammatory, and anti-amyloidogenic properties that may complement donepezil's cholinesterase inhibition.

Research design and methods: We employed the elav-Gal4/UAS-hAPP-BACE-1 Drosophila melanogaster model alongside molecular docking simulation and ADMET prediction to evaluate curcumin-donepezil combination versus monotherapy. Fruit flies received the treatment regimen, and were tested for survival, memory performance, and biochemical markers, including BACE-1 activity and oxidative stress parameters.

Results: Combination therapy significantly improved survival rates and memory performance compared to individual treatment. The combination effectively modulated multiple AD-related pathways, demonstrating reduced BACE-1 activity and decreased oxidative stress markers. Molecular docking confirmed favorable drug interactions, and ADMET profiles supported therapeutic viability.

Conclusions: Curcumin-donepezil combination therapy shows promise as a multi-target approach for AD management. However, translation to clinical applications requires validation in higher-order models and human trials.

Introduction: Parkinsonian symptoms are one of the core features of Dementia with Lewy bodies (DLB), which has a prevalence of more than 80%. Management of DLB poses unique challenges as the treatment of one condition leads to the worsening of another. Rivastigmine's efficacy and tolerability for cognitive and neuropsychiatric symptoms are well-studied. However, its effect on parkinsonian symptoms of DLB is inconclusive.

Clinical case series: In this case series, we elucidated five clinically diagnosed subjects of DLB with varying severity of parkinsonian motor symptoms. Beyond the cardinal signs of parkinsonism (tremor, rigidity, bradykinesia); rigidity, hypomimia, and gait disturbances were common in all the subjects. All five subjects on Rivastigmine dosage of 3-4.5 mg/day showed a greater than 50% reduction in the Unified Parkinson's Disease rating scale part III without any untoward side effects. Hypomimia, stiffness, gait, and postural abnormalities were the motor signs that were substantially improved while resting tremors showed the least improvement.

Discussion: The study findings focus on the need to reflect upon the non-cholinergic deficiency hypothesis in developing motor symptoms in DLB. The distinct pathophysiology of DLB and the complex interactions of cholinergic and dopaminergic neurons in the striatum can explain the improvement in parkinsonian symptoms with Rivastigmine.

Conclusion: This case series highlights the positive effect of low-dose Rivastigmine on parkinsonian motor symptoms of DLB prompting the need for further multicentric trials.

Background: Alzheimer's disease (AD) is considered to be one of the neurodegenerative diseases with possible cognitive deficits related to dementia in human subjects. High priority should be put on efforts aimed at early detection of AD.

Research design and methods: Here, images undergo a pre-processing phase that integrates image resizing and the application of median filters. After that, processed images are subjected to data augmentation procedures. Feature extraction from WOA-based ResNet, together with extracted convolutional neural network (CNN) features from pre-processed images, is used to train proposed DL model to classify AD. The process is executed using the proposed Attention Gated-VGG model.

Results: The proposed method outperformed normal methodologies when tested and achieved an accuracy of 96.7%, sensitivity of 97.8%, and specificity of 96.3%.

Conclusion: The results have proven that Attention Gated-VGG model is a very promising technique for classifying AD.

Background: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder with diverse symptoms that complicate diagnosis. We aimed to characterize MSA-related symptoms, medications, and healthcare resource utilization (HCRU).

Research design and methods: This retrospective cohort study used a large US claims database. Newly diagnosed patients >30 years old with ≥2 MSA diagnosis (2017 - 2021) were matched to controls. Endpoints related to MSA symptoms, prescriptions, and HCRU were compared between the two groups during the first year after diagnosis. Conditional logistic regression models examined the association between each outcome and MSA.

Results: A total of 1187 MSA patients and 4748 matched-controls were compared. MSA patients had significantly higher rates of various symptoms, respectively (OR and 95% CI): orthostatic hypotension (38.7% and 0.8%; 89.6, 57.3 - 140.2); memory disorders (22.4% and 3.6%; 9.2, 7.3 - 11.6); motor symptoms (78.1% and 33.1%; 7.5, 6.4 - 8.7); falls (11.1% and 2.2%; 6.4, 4.8 - 8.5); fatigue (46.6% and 13.6%; 5.8, 5.0 - 6.7); mood disorder (62.3% and 24.2%; 5.5, 4.8 - 6.4); and urinary dysfunction (30.8% and 9.1%; 4.9, 4.1 - 5.8), among other. They also received more medications for these conditions and had higher rates of hospitalizations and other HCRU.

Conclusions: This real-world study of MSA-related symptoms, treatments, and HCRU demonstrates the significant disease burden associated with MSA.

Alzheimer's disease (AD), the most common form of dementia, remains a leading neurodegenerative disorder that necessitates the development of diagnostic markers. While current cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers facilitate diagnostic accuracy, their invasive and pricey nature limits widespread application. Blood-based biomarkers, such as plasma Aβ42/40 and phosphorylated tau isoforms, are emerging as accessible alternatives. Biomarkers reflecting neurodegeneration (e.g. neurofilament light chain, brain-derived tau) and neuroinflammation (e.g. glial fibrillary acidic protein, TSPO-PET) provide additional insights into disease progression. Novel approaches - including exosomal and Aβ seeds biomarkers, omics techniques, and retinal imaging - further broaden the diagnostic landscape. Despite the promising perspectives, challenges remain in validity and utility. This review highlights recent advances of AD diagnostic markers, evaluates their clinical potential and limitations, and outlines future directions guided by the Geneva five-phase roadmap. The ultimate aim is to facilitate earlier detection and timely intervention of this burdensome disorder.

Background: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.

Methods: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20 years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.

Results: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.

Conclusion: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.

Objectives: We investigated the relationship between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) and amyotrophic lateral sclerosis (ALS) outcomes.

Methods: We enrolled ALS patients diagnosed between January 2014 and December 2019. Experienced neurologists followed up the participants until January 2022. Absolute difference between eGFR (eGFRabdiff) and relative difference between eGFR (eGFRrediff) were obtained. Cox proportional hazard models were used to evaluate the relationship between eGFRdiff and ALS survival.

Results: Negative eGFRabdiff were common in the patients (74.7%). For each SD increase of eGFRabdiff, the risk of poor prognosis for ALS patients decreased by 1.9% (HR, 0.981; 95% CI, 0.973-0.989). For each 10% increment in eGFRrediff, the risk of poor prognosis for ALS patients decreased by 17.7% (HR, 0.823; 95% CI, 754-0.898).

Conclusions: We found that large eGFRdiff was associated with poor prognosis in ALS. Monitoring eGFRdiff in ALS population facilitates prognostic stratification assessment and precise management.

Aim: To evaluate the effects of isokinetic hamstring and quadriceps muscle (IHGM)-strengthening and home exercises on balance, proprioception, fear of falling (FoF), kinesiophobia, and quality of life in persons with multiple sclerosis (PwMS).

Methods: The peak torque/body mass of the IHGMs, the absolute angular error (AAE) and mean AAE of the less and more affected legs, and the scores of the Dynamic Gait Index, 10-meter walk test, Berg Balance Scale (BBS), Modified Falls Efficacy Scale, Multiple Sclerosis Quality of Life-54 (MSQoL-54), Visual Analog Scale, and Tampa Scale of Kinesiophobia-17 (TSK-17) were evaluated before and after the training programs.

Results: Isokinetic exercises resulted in significantly higher improvements in the BBS (p = 0.008) and MSQoL-54 physical (p = 0.006) scores and the quadriceps muscle strength at 180°/s angular velocity in the less affected leg (p = 0.001) compared to home exercises.

Conclusions: Isokinetic exercises can improve muscle strength, QoL, and balance in PwMS without complications or exacerbations.

Hereditary transthyretin amyloidosis is a progressive life-threatening disease characterized by deposition of abnormally folded amyloid fibrils into tissues leading to polyneuropathy and cardiomyopathy. Eplontersen, an antisense oligonucleotide has been FDA approved for the treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States. Eplontersen inhibits the translation of both variant and wildtype transthyretin in the liver, thereby preventing deposition in tissues. In the pivotal Phase III NEURO-TTRansform trial, Eplontersen significantly lowered serum transthyretin concentrations, improving neuropathic impairment and quality of life. Eplontersen was generally well tolerated in the treatment group, with the primary safety effects not significantly different from the control group. Eplontersen is suitable for long term use in patients with disease related polyneuropathy and is currently being studied for use in patients with cardiomyopathy. In this review, we discuss the clinical efficacy, mechanism of action, pharmacology, tolerability, and social determinants of health affecting the use of Eplontersen.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.

Methods: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.

Results: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.

Conclusion: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.