Neurodegenerative disease management最新文献

Background: Degenerative cerebellar disorders (DCDs) are a group of conditions that involve deterioration of neurons in the cerebellum. People with DCDs (PwDCD) present with multifaceted symptoms across motor (e.g., ataxia, imbalance, impaired gait) and cognitive systems (e.g., altered executive functioning, communication, emotional regulation, and visuospatial skills). The impact of exercise and physical activity on improving cognitive deficits has been investigated in many neurodegenerative conditions including DCDs; however, there is limited evidence for the impact of cognitive impairments in PwDCD on the ability to engage in regular exercise.

Methods: This narrative review explores literature related to cognition and exercise in PwDCD, as well as a wider range of neurodegenerative disorders.

Results: We discuss potential cognitive factors contributing to barriers in exercise engagement in PwDCD, as well as highlighting current research regarding the importance of exercise engagement, and ways to overcome barriers to exercise in PwDCD.

Conclusions: While evidence is limited, we highlight the effects of cognition on exercise and suggest future directions to foster multidisciplinary collaboration in DCD management.

Aim: Ozanimod is a second-generation sphingosine 1-phosphate receptor (S1PR) modulator approved for treatment of relapsing multiple sclerosis (MS). Data are lacking for ozanimod use in real-world clinical practice. This study aims to determine characteristics of people with MS (pwMS) prescribed ozanimod as well as ozanimod persistence, tolerability, safety, and effectiveness over one year.

Methods: Data were retrospectively collected for adults with MS or clinically isolated syndrome who received ozanimod at two tertiary MS centers.

Results: We identified 206 pwMS for inclusion. Many (n = 146, 71%) had prior disease-modifying therapy (DMT) experience. The most common reasons for switching to ozanimod were cost (n = 48, 33%) and prior DMT intolerance (n = 29, 20%). Most individuals (n = 149, 72%) remained on ozanimod at last data collection. The most frequent reason for discontinuation was side effects (n = 21, 37% of discontinuers, 10.2% of total cohort). Few pwMS reported tolerability concerns (7.5% at 12 months). When comparing pre-ozanimod baseline to 12-month data, the annualized relapse rate was reduced by 56% (p = 0.034), and fewer pwMS had new/enlarging brain MRI T2 lesions (6.6% versus 40%, p < 0.001) and gadolinium-enhancing lesions (3.9% versus 27%, p = 0.027).

Conclusion: Ozanimod was well-tolerated with good treatment persistence, a favorable safety profile, and reductions in clinical and radiographic disease.

Introduction: Pain and fatigue are frequent symptoms in individuals with Amyotrophic Lateral Sclerosis (ALS) and the literature is controversial regarding the effectiveness of physiotherapy practices for managing these symptoms.

Objective: To analyze the profile of pain and fatigue symptoms in a Brazilian sample with ALS and identify physiotherapy practices.

Methods: A multimethods study composed of prospective cross-sectional design and systematic retrospective design. Data on pain and fatigue were collected and literature searches were conducted and risk of bias (PEDRro scale) and evidence quality (SIGN system) were evaluated.

Results: The sample (72 individuals) had a mean score of 4.31 (pain) and 37.2 (fatigue), indicating moderate levels of symptoms. The systematic review identified various physiotherapy practices for treating pain and fatigue.

Conclusion: Prospective analysis of pain and fatigue profiles in individuals with ALS in Brazil revealed moderate levels of both symptoms. The systematic retrospective analysis indicated uncertainty regarding the effect of physiotherapy.

Aims: To assess the impact of an Expert Patient Program on the quality of life and lifestyle habits of multiple sclerosis patients and their caregivers from Costa Rica, Honduras, and Dominican Republic.

Materials & methods: Quasi-experimental design, with repeated measures, without control group. The sessions taught self-care, problem-solving, nutrition, physical activity, fatigue, sleep, pain, and emotions. Data was collected using online questionnaires, such as the Short Version of the World Health Organization Quality of Life questionnaire. Data analysis included Student's t-test for related samples and Cohen's d.

Results: 65 cases, with 75.4% patients. Participants increased adherence to healthy lifestyle habits, physical activity, and reduced sedentarism. Those living with the disease for more than five years improved the physical (p = 0,019) and psychological domains (p = 0,008), while individuals with lower education levels improved their environmental domain (p = 0,005).

Conclusion: This pilot study provides evidence supporting the impact of this Program on quality of life.

Aims: To examine how specific non-motor symptoms (NMS) are associated with physical activity engagement in individuals with Parkinson's disease (PD).

Materials and methods: Data from 24,813 individuals with PD were obtained from the Fox Insight dataset (Michael J. Fox Foundation). Variables included sex, age, disease duration, Physical Activity Scale for the Elderly (PASE), and Non-Motor Symptoms Questionnaire (NMSQ). Ridge regression and linear modeling were used to assess associations between NMS and PASE scores.

Results: Delusions, falls, apathy, leg swelling, hallucinations, bowel incontinence, depressive mood, dysphagia, difficulty concentrating, and constipation were significantly associated with lower PASE scores. Female sex, older age, and longer disease duration were also linked to reduced physical activity. The model explained 10.51% of the variance in PASE scores.

Conclusions: Specific NMS are linked to reduced physical activity in PD. Targeting these symptoms may help increase activity levels and improve quality of life.

Frataxin is an evolutionarily conserved mitochondrial protein essential for energy metabolism. Biallelic GAA repeat expansions in the FXN gene reduce frataxin expression, causing Friedreich's ataxia. Frataxin deficiency impairs key mitochondrial metabolic enzymes, leading to widespread mitochondrial dysfunction with disrupted glucose and fatty acid oxidation. Although systemic mitochondrial dysfunction affects multiple organ systems, neurological deficits are the only feature uniformly observed in all FRDA patients. This review highlights recent insights into the neuropathology of FRDA, emphasizing the detailed developmental timing of neuroanatomical changes. It also focuses on selective mitochondrial metabolic pathways, including fatty acid metabolism, ceramide synthesis, and ketogenesis, which may underlie neuron-specific vulnerability and serve as potential targets for pharmacological or dietary intervention. The possibility of non-traditional interventions based on metabolic features of FRDA offers hope for ameliorating the severity of FRDA.

Background: Fatigue affects up to 95% of individuals with multiple sclerosis (MS), significantly impairing daily functioning. Management is multidisciplinary, and although amantadine lacks U.S. FDA approval for this indication, it remains the most commonly prescribed pharmacologic option despite inconsistent supporting evidence. This systematic review and meta-analysis evaluated the effectiveness of amantadine for MS-related fatigue.

Design/methods: We searched MEDLINE, EMBASE, and Web of Science for randomized controlled trials (RCTs) comparing amantadine to placebo in the treatment of MS-related fatigue. Statistical analyses were conducted using R. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess fatigue severity and adverse effects incidence, respectively. A random-effects model was applied to all analyses.

Results: A total of nine RCTs were included, involving 601 patients, 66% of whom received amantadine. Amantadine use was not associated with a significant reduction in fatigue severity compared to placebo (SMD -0.22; [95% CI -0.72; 0.27]; p = 0.37). However, it was associated with higher odds of insomnia (OR = 2.33; [95% CI 1.27; 4.29]; p = 0.006).

Conclusion: This meta-analysis suggests that amantadine is not effective for treating MS-related fatigue and is associated with an increased risk of adverse effects, particularly insomnia. These results cast doubt on its continued first-line use.

Background: Motor neuron disease (MND) is a rare, fatal neurodegenerative disorder associated with high mortality and disability, posing a significant healthcare burden. This study analyzed the United States mortality trends from 1999 to 2020 using data from the CDC WONDER database.

Methods: A retrospective analysis was conducted, calculating age-adjusted mortality rates (AAMRs per 100,000) and annual percentage changes, with stratification by age, sex, race, and census region.

Results: There were 140,805 MND-related deaths during the period. The overall mortality rate remained stable from 1999-2015 and 2016-2020. Rates varied significantly by age, being highest in the 75-84 group and lowest in the 25-34 group. Mortality was highest among males and non-Hispanic whites. The AAMR was also highest in the Midwest and in rural areas.

Conclusion: In conclusion, while overall MND mortality in the U.S. was stable, the age-adjusted rate was highest among men, non-Hispanic whites, and rural populations in the Midwest, and increased with age. This underscores the need for targeted interventions, including education, environmental improvements, enhanced healthcare access, and screening promotion for high-risk groups.

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.