Neurodegenerative disease management最新文献

Background: Gait analysis is essential tool for tracking neurological disorders-Parkinson's disease (PD), stroke, Alzheimer's disease (AD), and multiple sclerosis (MS). Wearable technologies enable continuous, noninvasive gait tracking beyond clinical settings but face challenges in accuracy and adoption. This review investigates wearable gait assessment, identifying patterns and future needs.

Methods: This rapid umbrella review was conducted, synthesizing systematic reviews and meta-analyses of wearable technologies for gait assessment in PD, stroke, AD, and MS. Following PRISMA guidelines two reviewers screened, extracted data on gait outcomes, and assessed quality using AMSTAR-2.

Results: Seventeen reviews (13systematic, 4meta-analyses) encompassing 308 primary studies were included. Most focused-on PD (n = 12), followed by stroke (n = 8), MS (n = 4), and AD (n = 2). Gait was primary outcome, alongside balance, fall risk, and mobility. Wearables (e.g. inertial sensors,) showed good diagnostic accuracy. Real-time biofeedback and exoskeletons improved function. Sensor placement differed greatly, usability was underreported.

Conclusions: Lack of standardization, validation, and usability limits clinical adoption. Future efforts must prioritize real-world testing and user-centered design.

Background: Parkinson's disease (PD) involves progressive motor and non-motor decline, linked to oxidative stress and glutathione depletion. N-acetylcysteine (NAC), a glutathione precursor and antioxidant, is a potential disease-modifying therapy.

Objective: To evaluate preclinical and clinical evidence on NAC in PD, focusing on motor and non-motor outcomes, dopaminergic function, and oxidative stress biomarkers.

Methods: A PRISMA-compliant review of MEDLINE and Embase (May 2025) identified prospective studies in animal models or adults with PD. Outcomes included Unified Parkinson's Disease Rating Scale (UPDRS), dopamine transporter (DAT) imaging, glutathione levels, and safety.

Results: Twelve studies met criteria. Preclinical models showed consistent neuroprotection. Intravenous NAC raised brain glutathione levels; high-dose oral NAC reached CSF. Two open-label trials (n = 65), reported ~ 13% improvement in UPDRS scores and 4-9% dopamine transporter signal increases over three months. No serious adverse events were attributed to NAC.

Conclusions: Larger randomized controlled trials are needed to test efficacy and disease-modifying potential.

Aim: This study aims to systematically evaluate and synthesize preclinical evidence on the neuroprotective effects of Triptolide (Tri) in Alzheimer's disease (AD) models, focusing on its impact on amyloid-beta accumulation, synaptic dysfunction, neuroinflammation, oxidative stress, autophagy, and apoptosis.

Introduction: AD is the most common cause of dementia, yet current treatments largely target symptoms rather than underlying pathology. Tri, a bioactive compound from Tripterygium wilfordii, has shown promise due to its anti-inflammatory, antioxidant, and neuroprotective properties.

Methods: A systematic search of PubMed, Embase, and Web of Science was conducted up to 16 March 2024. English-language in vivo and in vitro studies on Tri's effects in AD models were included. Methodological quality was assessed using SYRCLE and SciRAP tools. The review is registered in PROSPERO (CRD42024521822).

Results: Out of 403 studies, 15 met the inclusion criteria (6 in vivo, 8 in vitro, 1 both). Tri reduced Aβ burden, enhanced memory and synaptic integrity, suppressed neuroinflammation and oxidative stress, and modulated autophagy and apoptosis.

Conclusion: Tri demonstrates significant multi-target neuroprotective effects in AD preclinical models. Further high-quality studies are warranted to optimize dosing, delivery, and safety for clinical translation.

Parkinson's disease is a neurodegenerative disorder of aging with dopaminergic neuronal degeneration in the substantia nigra leading to motor dysfunction. Mitochondrial dysfunction is central to its pathophysiology, leading to oxidative stress, derangement of energy metabolism, and induction of neuronal apoptosis. Current therapeutic interventions are symptomatic but fail to stop disease progression. Stem cell-based regenerative strategies have been recognized as potential disease-modifying treatments. Mitochondria-augmented stem cell therapy offers a new mechanism for the correction of cellular bioenergetic deficits. Through genetic manipulations or preconditioning protocols, mesenchymal stem cells and induced pluripotent stem cells are engineered to enhance mitochondrial function and transfer. The engineered cells enable delivery of functional mitochondria into damaged neurons through tunneling nanotubes or extracellular vesicles, promoting ATP production, inhibiting reactive oxygen species, and restoring mitophagy. Preclinical models have demonstrated improved neuronal survival and motor function, and novel technologies like CRISPR gene editing and 3D bioprinting offer improved translational relevance.

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.