Neurodegenerative disease management最新文献

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.

Background: Carbidopa/levodopa (CD/LD) remains the primary treatment for Parkinson's disease (PD) motor control symptoms. With progressing disease, for better symptom management, patients often split immediate-release CD/LD tablets-research on this practice is limited.

Objective: Survey patients with PD/caregivers, and neurologists on CD/LD pill-splitting practices and motor complications' impact on quality of life (QoL).

Methods: We surveyed 101 patients/caregivers and 120 neurologists.

Results: All agreed that motor control symptoms substantially affect QoL, particularly as PD progresses. 47% of patients surveyed halved immediate-release CD/LD tablets, and 27% fragmenting them further, with 27% and 18% finding it easy and accurate, respectively. Pill splitters reported longer disease duration, more advanced PD, worse motor fluctuations/dyskinesia control, and QoL. Neurologists reported dissatisfaction with CD/LD treatments for advanced disease, noting 44.9% of patients split tablets with, and 21.9% without, physician recommendation.

Conclusions: Pill splitting is common but burdensome and imprecise. Further research is needed to evaluate clinical impact.

Aim: Compare three straight-path configurations of the six-minute walk test (6MWT) in persons with Parkinson disease with and without freezing of gait (FOG).

Materials & methods: Experiment 1 participants performed the 30-m standardized and 7.5-m straight-path configurations of the 6MWT. Experiment 2 participants performed the 30-m standardized and 15-m straight-path configurations of the 6MWT. Tests were performed a week apart at the same time of day.

Results: Participants walked 60 meters less in the 7.5-m than in the 30-m configuration (p < .001), and those with FOG walked 108 meters less than those without FOG (p = .044). Participants walked 12 meters less in the 15-m than in the 30-m configuration (p = .046).

Conclusions: When limited clinic space prevents setup of the standard 30-m configuration of the 6MWT, shortening the configuration to less than 15 meters may result in substantially smaller outcomes that are not comparable to published norms for persons with Parkinson disease.

Introduction: Dysphagia is common among individuals with Progressive Supranuclear Palsy (PSP). Expiratory muscle strength training (EMST) is a treatment used to increase expiratory muscle force production for airway protection deficits. To our knowledge, no studies have tested EMST in this population. The objective of this study was to determine the feasibility of EMST in individuals with PSP.

Methods: Twenty-nine participants completed baseline measures of maximum expiratory pressure and underwent a trial session of EMST. EMST was considered feasible if participants were able to complete at least 10 repetitions at 30% of their maximum expiratory pressure. Qualitative analyses were also completed to investigate types and frequency of clinician support.

Results: Twenty-seven participants (93%) successfully met the criteria for feasibility of EMST. Qualitative analysis revealed 20 individuals required clinician support with most requiring more than one type of assistance.

Conclusions: EMST appears to be feasible for most people with PSP though additional clinician support is often required.

Background: Quality of life is an important goal of care for people living with amyotrophic lateral sclerosis (ALS) and their carers. The ALS Specific Quality of Life instrument Short Form (ALSSQOL-SF) has been translated and validated in various cultural contexts, however its utility in the Malaysian cultural context has not yet been evaluated.

Methods: The quality of life of 21 patients with ALS was evaluated using the ALSSOL-SF in either the English version or translated to the Malay language. A cognitive interview approach was utilized and the responses were transcribed and thematically analyzed.

Results: Culture and language-related factors affecting the application of the ALSSQOL-SF were identified. Interpretations of intimacy and religiosity varied and sometimes differed significantly from the constructs underlying the ALSSQOL-SF domains.

Conclusion: The ALSSQOL-SF captured items from the physical domain better than those from the psycho-social and spiritual domains. Cognitive interviewing showed that patients mostly could not grasp the intended meaning of the items from the psycho-social and spiritual domains despite translation into the Malay language. There are limitations in adapting the ALSSQOL-SF for use in evaluation of QOL in Malaysian ALS patients. In the local setting a better understanding is needed about how aspects such as religion, intimacy and spiritual well-being are culturally reflected and expressed.

Neurodegenerative disorders (NDDs), characterized by gradual decline of neuronal function and structure, present a major threat to global public health. Recent advances in neuropharmacology have opened promising avenues for novel therapeutic approaches. This review highlights promising neuropharmacological targets that may alleviate the debilitating effects of neurodegenerative disorders. This review examines established yet emerging molecular targets in neurodegeneration, including protein aggregation, synaptic dysfunction, oxidative stress, neuroinflammation, and Rho-associated protein kinase (ROCK) signaling. The review also explores ground-breaking therapeutic strategies that have transformed modern neuropharmacology. Recent advances in nanotechnology, gene therapy, immunotherapy, and in silico studies have revolutionized neurotherapeutics by enabling precise drug delivery, enhancing treatment efficacy, and facilitating personalized therapies. These innovations have also accelerated the discovery of novel compounds and improved prediction of therapeutic outcomes.

Purpose: To evaluate treatment perceptions of diroximel fumarate (DRF) for relapsing multiple sclerosis (MS), with contextual data from dimethyl fumarate (DMF) users, based on patient and healthcare provider (HCP) surveys.

Methods: A prospective web-based survey was conducted among MyMSTeam users aged ≥ 21 years in the United States, who provided information about their MS disease and treatment history. The Spherix HCP survey collected retrospective chart data from HCPs for patients who switched disease-modifying therapies (DMTs).

Results: Of 535 MyMSTeam respondents, 77 (14%) received DMF and 46 (9%) received DRF. DRF users reported physical and emotional benefits such as slowed disease progression, decreased relapses, and new symptom prevention, with 70% noting at least one physical benefit and 46% reporting emotional/quality of life benefits. Additionally, 83% found DRF tolerable. HCPs reported prescribing DRF due to good tolerability (58%) and a preference for oral administration (50%). The most common reasons for switching to DRF were lack of efficacy (52%) or poor tolerability (49%) of previous DMTs.

Conclusion: A real-world, patient-focused survey on MS treatment suggested DRF was well tolerated and associated with patient-reported physical benefits. HCP-reported reasons for selecting DRF included efficacy and tolerability issues with prior DMT.

Fruits' popularity has grown due to their ability to protect against neurodegenerative illnesses and to be an important dietary component for good brain activity. This review focuses on fruits' potential for preventing such, taking into account their bioactive compounds and mode of action. It emphasizes the abundance of flavonoids, polyphenols, vitamins, and minerals found in berries, citrus, and other tropical fruits, which have been shown to reduce oxidative damage, prevent neuroinflammation, and improve synaptic plasticity. There is an extensive literature on the neuroprotective actions of compounds such as resveratrol, quercetin, and anthocyanins in neurogenesis and mitochondrial process functions. The review also mentions emerging literature with the gut-brain axis, where it underscores the way in which fruit-derived prebiotics and dietary fibers regulate gut microbiota, which in turn affects brain health. This study analyzes gaps by adopting a comprehensive approach to studying fruits' preventive power in the treatment of neurodegenerative illness. This study combines molecular biology, clinical trial, and dietary science findings to highlight the use of fruits in ordinary diets as a sustainable, natural way of promoting neuroprotection and slowing the course of NDs.

Background: Autonomic dysfunction is a common non-motor symptom of Parkinson's disease (PD). However, reliable biomarkers for predicting autonomic symptoms in PD remain unidentified. Neurofilament light chain (NfL), a biomarker of neuronal impairment, is closely correlated with disease progression in PD.

Objective: This study examines the relationship between serum NfL levels and autonomic impairment in patients with early-stage PD.

Methods: A total of 312 patients with PD were included in the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic symptoms were assessed using the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). Kaplan-Meier survival analysis and linear mixed-effects models were used to evaluate associations between serum NfL and autonomic symptoms.

Results: Higher baseline serum NfL levels were significantly associated with increased SCOPA-AUT scores and greater autonomic symptoms over time. Patients with the highest tertile of baseline serum NfL levels had an increased risk of developing OH over the five-year follow-up period (p = 0.004). However, the rate of NfL change was not significantly associated with autonomic symptoms progression.

Conclusions: Elevated baseline serum NfL levels may be a valuable biomarker for predicting autonomic symptoms in early-stage Parkinson's disease, which might be a new target in disease monitoring and early intervention.