Neurodegenerative disease management最新文献

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.

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.

Aims: This retrospective cohort study describes real-world safety and tolerability outcomes in United States-based edaravone-treated patients with ALS.

Patients & methods: Amerita Specialty Infusion Services provided IV edaravone to patients with ALS treated with their first dose between 25 September 2017-30 September 2022. Mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) %-predicted measures were recorded within ± 100 days from care initiation to approximate baseline values.

Results: Included patients (n = 243) received/were still receiving IV edaravone/edaravone oral suspension as of 30 September 2022. At initiation, 66.7% were male, mean age ± SD was 61.2 ± 11.2 years, and 61.3% were covered by government insurance. In patients with provider-recorded ALSFRS-R (n = 115) and FVC (n = 84) %-predicted measures within ± 100 days from care initiation, mean ± SD values were 35.1 ± 8.9 and 72.3% ± 21.7%, respectively. Mean ± SD therapy duration was 13.5 ± 11.4 months. Discontinuation reasons included death/hospice (n = 82), patient's choice (n = 38), doctor's choice (n = 31), insurance (n = 18), and other (n = 12). Reasons for IV edaravone discontinuation and IV edaravone administration access device were not associated.

Conclusions: Treatment discontinuation was primarily related to ALS disease progression/death, rather than safety or tolerability. This study representative of real-world patients with ALS suggests that edaravone showed consistent safety and tolerability profiles with previous studies.

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.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder. Hypokinetic dysarthria, a motor speech disorder affects approximately 90% of PD patients. In Morocco, linguistic features of Moroccan Arabic may influence how voice impairment appear in PD. This study investigates the acoustic characteristics of Moroccan PD patients' voices. This was a case-control study involving 30 Moroccan PD patients, both medicated and unmedicated) and 30 healthy control participants. Voice recordings were collected from participants before and after dopaminergic treatment. Four tasks were performed: sustained vowel production, spontaneous speech, diadochokinesis, and reading tasks in both Arabic and French. The Unified Parkinson's Disease Rating Scale was computed for each state and data were analyzed using PRAAT software (v6.2), for phonatory and articulatory parameters. PD patients exhibited significant alterations in shimmer, jitter, and Harmonics-to-Noise and Noise-to-Harmonic Ratios, reflecting pitch and vocal intensity instability. A "hoarse" and "breathy" vocal quality was noted. Rhythm disturbances were marked by an increased number of long pauses (≥500 ms), indicating difficulty in sustaining speech flow. No adverse events were reported. Moroccan PD patients exhibit distinctive voice and rhythm abnormalities, particularly in vowel articulation, phonation, and timing. These markers may serve as reliable indicators for PD diagnosis and progression.

Multiple sclerosis [MS] is an immune-mediated disease driven by peripherally mediated and central nervous system compartmentalized pathophysiologic processes. Major advances have led to a plethora of disease modifying therapies [DMTs] available for the treatment of MS. Among the wide range of DMTs, the immune reconstitution therapies [IRTs] are a unique subset of therapy that have the potential for durable benefit without the need for chronic administration. Cladribine tablets are a higher-efficacy oral IRT that selectively targets lymphocytes, causing a transient lymphopenia, followed by immune reconstitution of a different repertoire of lymphocytes that may result in durable benefit. The intermittent dosing schedule and efficacy in reducing measures of disease activity in both the short and long-term make cladribine an attractive DMT choice for a broad range of individuals with relapsing forms of MS. This narrative review summarizes the available efficacy and safety data from clinical trials and real-world studies on cladribine tablets.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no known cure, affecting both motor and non-motor functions. This review examines the therapeutic potential of dance as a holistic intervention to complement conventional PD treatments.

Methods: This systematic review followed PRISMA guidelines. Studies included were randomized controlled trials, longitudinal studies, and meta-analyses evaluating dance interventions in PD. Databases searched included PubMed, Scopus, and Web of Science. Exclusion criteria were case studies and non-peer-reviewed sources.

Results: Sixty-six studies involving over 1,200 participants were identified. Evidence shows that dance improves motor functions such as gait, balance, and coordination, while also enhancing non-motor outcomes including mood, anxiety, depression, and cognition. Dance's rhythmic movements, cognitive demands, and social interaction stimulate neurochemical pathways linked to motor and emotional regulation. Furthermore, group dance fosters social connectedness and reduces isolation. Online and community-based programs demonstrate feasibility and accessibility across diverse populations.

Conclusions: Dance provides multidimensional benefits for individuals with PD, spanning physical, cognitive, emotional, and social domains. Despite these promising findings, limitations such as small sample sizes, methodological heterogeneity, and lack of direct comparisons with other exercise modalities remain. Larger standardized trials are needed to confirm efficacy and support integration of dance into PD treatment programs.

Background: To identify if a combination of blood-based biomarkers related to inflammation and oxidative stress predict treatment response to nabilone for Alzheimer's disease (AD)-associated agitation.

Research design and methods: Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Serum concentrations of 13 markers were quantified. Univariable and multivariable regression were used to determine differences in CMAI change given nabilone and placebo. A model combining biomarkers with clinical predictors was also evaluated.

Results: Overall, 38 participants enrolled in the original trial (76% male, mean ± SD age 87 ± 10). Nabilone was more efficacious in participants with higher IL-6, higher 8-ISO, higher 24S-OHC, and lower clusterin. Participants in the first tertile (T1) of index scores demonstrated better response to nabilone compared to placebo with a mean difference in CMAI change of -20.6 (95%CI: -30.3, -10.4). During the nabilone phase, 83% of participants in T1 were responders versus 38% in T2 + 3 (Fisher's p = .01). In the combined model, T1 showed better response to nabilone with a mean difference in CMAI change of -26.4 (95%CI: -34.0, -19.6). The proportion of responders was significantly higher in T1 (91%, n = 11) compared to T2 + 3 (32%, n = 19) (Fisher's p = .002).

Conclusion: A combination of biomarkers could help characterize responders and non-responders to nabilone.

Background: We designed this systematic review and meta-analysis to estimate a pooled odds ratio of developing MS by coffee consumption.

Methods: PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, and google scholar were searched by an expert researcher for articles published before January 2024. The gray literature including references from included studies, and conference abstracts was searched.

Results: The literature search revealed 521 articles; after deleting duplicates, 323 articles remained. Eight studies were included for meta-analysis. A total of 2193 MS cases and 2344 controls were evaluated. In cases, 1072 individuals were coffee users, while 1295 individuals in the control group were coffee consumers. The pooled odds ratio (OR) of coffee consumption and risk of MS was 0.78 (95%CI:0.69-0.88) (I² = 92.9%, p < 0.001).

Conclusion: Coffee consumption was associated with a lower risk of MS in pooled analysis, but the substantial heterogeneity limits the strength and generalizability of this conclusion. Larger, multi-centric studies are recomended.