Current Alzheimer research最新文献

Introduction: Dementia is the most common neurodegenerative disease, but the risk factors associated with its progression remain incompletely understood. Identifying clinical and medication-related determinants of cognitive decline may inform patient management and guide treatment strategies.

Materials and methods: Individuals with dementia who underwent paired Mini-Mental State Examination (MMSE) assessments between 2013 and 2019 were identified from the Taipei Medical University Clinical Research Database. To ensure adequate follow-up, paired assessments were required to be at least 90 days apart, with an actual mean follow-up interval of 21.5 ± 18.0 months. Demographic data, comorbidities, medication prescriptions, and blood biochemistry results were extracted. Generalized estimating equations were applied to evaluate associations between these factors and MMSE changes.

Results: A total of 3,054 individuals with dementia were included (mean age 78.0 ± 9.2 years, 61.1% women). The mean baseline MMSE score was 18.5 ± 6.7 and it declined to 16.0 ± 7.5 at follow-up. Male sex was significantly associated with greater MMSE decline (estimate: -0.920, 95% CI: -1.552 to -0.289, p = 0.004). Antidementia medications were significantly associated with less decline in MMSE scores (estimate: 1.245, 95% CI: 0.676 to 1.815, p < 0.001). In contrast, non-aspirin antiplatelet agent use was associated with a greater decline among men (estimate: -1.346, 95% CI: -2.518 to -0.173, p = 0.025).

Discussion: These findings highlighted that both clinical and pharmacological factors influence cognitive decline in dementia. Antidementia medications were linked to slower deterioration, supporting their role in disease management. Conversely, the association of non-aspirin antiplatelet agents with faster decline in men suggested potential adverse effects that warrant further investigation.

Conclusion: In this large real-world cohort, sex and medication use were key determinants of cognitive decline in dementia. Antidementia medications mitigated decline. Notably, only non-aspirin antiplatelet agents, but not aspirin, were associated with greater cognitive decline in men., underscoring the need for personalized treatment approaches.

Non-coding RNA (ncRNA)-based therapies represent an emerging and transformative approach in the treatment of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)/Motor Neuron Disease (MND). This review explored the potential for targeting microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, reinforced by promising results from clinical trials demonstrating their capacity to modulate disease pathways. The incorporation of cutting-edge computational methodologies, including RNA structure prediction and gene regulatory network analysis, has been at the forefront in enhancing the efficacy of ncRNA-based treatments. Moreover, chemical methods have improved RNA molecules' stability, accuracy, and directed delivery, enhancing their therapeutic effects. Moreover, cutting-edge RNA editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein 13 (CRISPR/Cas13) are advancing our ability to directly manipulate ncRNA expression, offering a powerful avenue for addressing the molecular origins of neurodegeneration. Despite these advances, challenges persist, particularly in ensuring the specificity, delivery efficiency, and long-term efficacy of these treatments. Nanotechnology provides innovative solutions to these obstacles, facilitating more efficient and precise RNA delivery, especially to neuronal tissue. In conclusion, ncRNA-based therapies, while still in nascent stages, represent a hopeful frontier in the fight against NDs. With ongoing research and technological advancements, these therapies could not only halt disease progression but also redefine the future of ND treatment, offering new avenues for patients' care and clinical success.

Neurodegenerative diseases comprise a heterogeneous group of disorders characterized by the progressive structural and functional deterioration of neurons in the central nervous system. Among them, Alzheimer's disease is the most prevalent worldwide. Despite their distinct clinical manifestations, many neurodegenerative disorders share convergent pathophysiological mechanisms such as protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, and neuroinflammation, which ultimately drive neuronal loss. These processes lead to profound impairments in cognitive performance, motor coordination, and overall functional capacity, making such diseases exceptionally difficult to diagnose early and manage effectively. Traditional treatment approaches administered orally or parenterally face limitations, including high hepatic metabolism, poor penetration across the blood-brain barrier (BBB), and systemic side effects. This review highlights the potential of the nose-to-brain (N2B) delivery system as an emerging and promising therapeutic strategy. N2B delivery utilizes the olfactory and trigeminal nerve pathways in the nasal cavity to rapidly and precisely deliver drugs to the central nervous system without crossing the blood-brain barrier. Because the system is non-invasive, it offers high bioavailability, reduced systemic exposure, and improved patient compliance. The use of lipid nanocarriers, nanoparticles, dendrimers, and nanogels to enhance the stability of drugs, facilitating efficient targeting and controlled release, is a crucial factor in optimizing N2B drug delivery systems. Various attributes influence drug transport, which are physiological, physicochemical and formulation-dependent characteristics. The main challenges faced by the N2B delivery system are enzymatic degradation and mucociliary clearance. Emerging technologies, such as AI, 3D Printing, and personalized medicine, all hold promise for future inventions in this area. Preclinical and clinical trials demonstrate the efficacy of delivering N2B in treating neurodegenerative diseases; however, its full potential remains to be seen due to regulatory, safety, and scalability concerns. Hence, this review emphasizes the research required to pursue interdisciplinary collaboration and unlock the full potential of N2B delivery, as well as a new approach to transforming neurodegenerative conditions.

Introduction/objective: Neurodegenerative diseases such as Alzheimer's disease (AD), Lewy dody dementia (LBD), and Parkinson's disease (PD) are linked to changes in brain volume. However, causal evidence on how these diseases affect brain volume and whether metabolites mediate these causal effects remains limited.

Methods: We applied mediation Mendelian randomization analysis using GWAS summary statistics. The inverse variance-weighted method was used to assess causal effects and identify potential metabolite mediators.

Results: The MR analyses indicated that bilateral thalamus and putamen volumes (FDR < 0.05) had causal effects on PD. AD and LBD showed causal effects on bilateral thalamus and hippocampus (FDR < 0.01), with LBD specifically showing a causal effect on bilateral putamen (FDR < 0.05). Mediation analyses revealed that AD had a genetically predicted association with Nervonoy- L-carnitine and 1-linoleoyl-2-arachidonoyl-GPC (p-value = 0.04 and 0.01, respectively). Moreover, Nervonoy-L-carnitine was suggestively negatively associated with hippocampus volume (p-value = 0.03 and 0.02, respectively). 1-linoleoyl-2-arachidonoyl-GPC exhibited a negative genetically predicted association with hippocampus volume (p-value < 0.05). Additionally, LBD showed a negative genetically predicted association on the ratio of retinol to linoleoyl-arachidonoyl- glycerol (p-value = 0.02), and a positive genetically predicted association on Nervonoy-L-- carnitine (p-value < 0.05) and 1-linoleoyl-2-arachidonoyl-GPC (p-value = 0.03).

Discussion: These results suggest that AD and LBD affect brain regions through causal pathways. The involvement of specific metabolites highlights potential mechanisms linking neurodegeneration to brain volume.

Conclusion: Nervonoylcarnitine and 1-linoleoyl-2-arachidonoyl-GPC may mediate the predicted effects of AD and LBD on hippocampal volumes, while the ratio of retinol to linoleoyl-arachidonoyl- glycerol mediates only LBD.

Introduction: Vagus Nerve Stimulation (VNS) has been approved by the FDA as a treatment for epilepsy, depression, post-ischemic stroke rehabilitation, and migraine in patients. It is emerging as a potential treatment for neurodegenerative diseases. Herein, we summarize the research on VNS and its application in common neurodegenerative diseases.

Methods: A literature search was completed in PubMed, ScienceDirect, and Google Scholar using the terms: "neurodegeneration," "neuromodulation," "Vagus Nerve Stimulation," "Parkinson's Disease (PD)," "Alzheimer's Disease (AD)," "dementia," "neuroinflammation," and "cognitive dysfunction." Animal and clinical studies using VNS as a primary intervention in neurodegenerative diseases were included.

Results: The studies of VNS application in Parkinson's and Alzheimer's models were reviewed. In animal studies, VNS was associated with increased locomotion and balance, as well as reduced cognitive impairments. The underlying neuroprotective mechanisms included: increased dopaminergic neurons, reduced α-synuclein concentration in the brain, preservation of the nigrostriatal dopaminergic pathway, increased α7nAChR expression, reduced apoptotic markers, reduced neuroinflammation, and significant reductions in microglial and astrocytic densities. In clinical studies with small patient populations of PD or AD/mild cognitive impairment, VNS was associated with improved gait parameters and enhanced performance in memory-based tasks.

Discussion: Vagus Nerve Stimulation (VNS) shows neuroprotective and anti-inflammatory effects in animal models of Alzheimer's and Parkinson's disease, but clinical results remain inconsistent due to variability in treatment duration, outcome measures, and reliance on subjective assessments. Emerging physiologic biomarkers such as VSEP, EEG, and magnetoencephalography may provide more objective measures of therapeutic response.

Conclusions: The systematic review highlights the potential of VNS as a therapeutic approach for managing neurodegenerative diseases. The efficacy of VNS in animal models of Parkinson's and Alzheimer's diseases involves both neuroprotection and anti-neuroinflammation, while additional protective mechanisms require further exploration.

Introduction: The relationship between Alzheimer's disease (AD) and normal-tension glaucoma (NTG) is an emerging area of interest owing to shared neurodegenerative features. Nevertheless, few studies have ascertained circulating microRNAs (miR) across both conditions. This study aimed to compare the expression of miR-128 and miR-455-3p in patients with NTG and AD and in controls, and to explore their potential as circulating biomarker candidates.

Materials and methods: In this cross-sectional study, serum miRNAs were extracted using a column- based kit and quantified by SYBR Green qRT-PCR (normalized to U6). Each reaction was run in triplicate. Data were analyzed via ANCOVA adjusted for age and sex, followed by Bonferroni post-hoc tests.

Results: Both miR-128 and miR-455-3p were significantly upregulated in the AD and NTG groups compared with controls (p < 0.001 for both). Adjusted mean expression for miR-128 was approximately 2.1 in AD, 2.6 in NTG, and 0.3 in controls, while the corresponding miR-455-3p values were 2.9, 3.1, and 0.8, respectively. Post-hoc comparisons confirmed higher expression in both disease groups compared with controls, but not between AD and NTG. Power analysis revealed >0.99 power for group comparisons with controls, consistent with robust group-level differences.

Discussion: miR-128 and miR-455-3p are implicated in neuronal stress responses, mitochondrial regulation, and amyloid-beta processing. Their parallel upregulation in AD and NTG suggests overlapping molecular signatures and may reflect systemic responses to neurodegenerative stress. These findings are also consistent with growing evidence that the eye and brain share vulnerability to similar cellular processes in neurodegeneration.

Conclusion: Elevated serum miR-128 and miR-455-3p in both AD and NTG indicate overlapping expression profiles across conditions. These miRNAs may serve as promising circulating biomarker candidates and support the concept of a molecular interplay between ocular and cerebral pathologies. However, their diagnostic and mechanistic potential warrants validation in largescale, longitudinal studies.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta (Aβ) peptides, especially the toxic Aβ42 isoform, which induces excessive reactive oxygen species (ROS) production leading to oxidative damage, lipid peroxidation, and neuronal loss. Given the critical role of oxidative stress in AD pathogenesis, antioxidants such as ascorbic acid (AA) are being explored for their therapeutic potential.

Objective: This study aimed to investigate the neuroprotective efficacy of ascorbic acid in a transgenic Drosophila melanogaster model expressing human Aβ42 in neuronal tissues.

Methods: Transgenic and wild-type flies were maintained on diets supplemented with optimized, non-toxic concentrations of AA. Biochemical assays were performed to evaluate oxidative stress and antioxidant defense, including glutathione (GSH) levels, glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content (PCC). Acetylcholinesterase (AChE) activity and locomotor performance were also assessed.

Results: Ascorbic acid supplementation significantly enhanced GSH levels, normalized GST, SOD, and CAT activities, and reduced TBARS and PCC levels, indicating restoration of redox balance. Partial recovery of AChE activity suggested protection of cholinergic neurotransmission. Functionally, AA-fed AD flies exhibited improved locomotor performance, delayed onset of memory impairment, and extended lifespan compared to untreated AD flies.

Conclusion: The findings demonstrate that ascorbic acid provides multifaceted neuroprotection by mitigating oxidative stress, stabilizing cholinergic function, improving behavioural outcomes, and enhancing longevity. AA emerges as a promising, low-cost natural antioxidant for potential use in Alzheimer's disease management.

Alzheimer's Disease (AD) is a neurodegenerative disorder accounting for 60-80% of dementia cases globally. Several risk factors are associated with increased AD onset, including genetics, physical activity, and varying levels of social interaction. Extensive research has explored potential treatments for AD, among which oxytocin (OX) has shown beneficial effects on memory-related neurological processes. OX has been suggested to modulate neuroplasticity within the hippocampus in rat and mouse AD models. Further studies indicate that intranasal administration of OX may lead to significant improvements in memory and cognition. In addition, a non-peptide agonistic analogue, LIT-001, has been investigated. This review aims to provide insight into the potential of OX as a therapeutic target for AD and to explore alternatives that activate similar cellular signaling pathways.

Introduction: Quality of life (QoL) in dementia care can be enhanced through nonpharmacological interventions. This systematic review and meta-analysis aimed to evaluate the effectiveness of such interventions across demographic groups in Saudi Arabia.

Methods: A systematic search identified 11 studies assessing sensory stimulation, mindful walking, functional independence, caregiver support, and public awareness interventions. Data were extracted on study design, population, and outcome measures. Three outcome studies were narratively synthesized.

Results: Sensory stimulation interventions (n = 62) showed the strongest behavioral improvements, with a large effect size (Hedges' g = -2.03). Data from other studies were insufficient for quantitative pooling, and no formal meta-regression or heterogeneity analyses were conducted.

Discussion: Findings suggest that behavioral and psychological interventions tailored to older adults yield the most significant QoL benefits. Caregiver support and awareness programs offer important supplementary benefits, although limited data restrict broader generalizations.

Conclusion: Non-pharmacological interventions, particularly those targeting behavioral and psychological outcomes, improve QoL in dementia care. However, further high-quality studies with comprehensive outcome reporting are needed to strengthen the evidence base and guide populationspecific strategies.

Alzheimer's disease is a neurodegenerative disorder characterized by impairments in cognitive functions such as thinking, behavior, and memory. The major pathological abnormalities associated with the disease include the formation of neurofibrillary tangles and amyloid plaques, which further cause neuroinflammation and nerve cell death. Currently, treatments for the disease focus on symptomatic management rather than addressing the root cause of neurological changes. Therefore, the current status of therapy highlights the need for more effective therapeutic substances that can either prevent abnormal deposition or slow neurodegeneration to preserve nerve cells. In this respect, ATP-sensitive potassium channel openers may have a potential role in prevention and protection. The present article focuses on several cellular mechanisms of this class, including the limitation of neuronal excitability, modulation of neurotransmitter release, prevention of aberrant protein buildup, reduction of excessive calcium influx, reduction of reactive oxygen species levels, and reduction of microglial activation.