Current Alzheimer research最新文献

{"title":"Associations between Handwriting Decline and Cognitive-Motor Impairment in Dementia.","authors":"Yury Chernov","doi":"10.2174/0115672050459901260112045555","DOIUrl":"https://doi.org/10.2174/0115672050459901260112045555","url":null,"abstract":"<p><strong>Introduction: </strong>Handwriting reflects the integration of cognitive and motor functions, making it a potential indicator of neurodegenerative changes. Handwriting deterioration often mirrors cognitive and motor decline in dementia, particularly Alzheimer's disease (AD). However, objective assessment methods remain limited. This study is based on the AD-HS instrument, which includes 42 handwriting features and three linguistic features. Their assessment is non-trivial. To ensure an objective and reliable evaluation, the features are given exact and unambiguous definitions. The formal, quantitative association of handwriting dimensions with cognitive and motor changes in dementia enriches previously published statistical results.</p><p><strong>Materials and methods: </strong>Handwriting samples from 53 individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) were analyzed against a reference group across six dimensions: spatial organization, letter formation, writing dynamics, stroke building, and overall appearance. Statistical analysis determined the significance of each dimension and its contribution to the overall AD-index (ADI).</p><p><strong>Results: </strong>The ADI effectively distinguished dementia samples from the reference group. The strongest diagnostic indicators were found in writing dynamics, followed by letter formation and spatial organization. The characteristics of early deterioration reflect cognitive impairment rather than purely motor impairment, which are less prevalent in the early stages.</p><p><strong>Discussion: </strong>Longitudinal data show that handwriting in early dementia deteriorates gradually, with diagnostic value arising from the combined presence of multiple affected features. The earliest changes appear in dynamic aspects, followed by spatial and organizational deficits, reflecting early cognitive disruption while motor programs remain largely intact. These findings support the validity of the AD-HS instrument for capturing handwriting changes associated with emerging dementia.</p><p><strong>Conclusion: </strong>The ADI offers a concise, quantitative measure of handwriting deterioration related to cognitive decline. Future research should focus on collecting longitudinal data and more strictly differentiating between age-related changes and cognitive decline.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Smell Disorder Diagnostics: A Comparative Review of Portable Test Kits and Self-Reported Tools.","authors":"Jayasurya Ramesh, Lakshmi Kanakaraj, Mohammad Badrud Duza","doi":"10.2174/0115672050427159251203090611","DOIUrl":"https://doi.org/10.2174/0115672050427159251203090611","url":null,"abstract":"<p><p><p> Olfactory Dysfunction (OD) is a prevalent yet underdiagnosed sensory disorder with profound implications for quality of life and for the early detection of neurodegenerative diseases such as Parkinson's and Alzheimer's. Beyond its sensory role, OD has emerged as an early, noninvasive biomarker of neurodegenerative pathology, often preceding measurable cognitive decline in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Quantitative smell loss correlates with pathological changes in the olfactory bulb and entorhinal cortex, highlighting its diagnostic potential for early screening and longitudinal monitoring. </p><p> Traditional diagnostic tools, though validated, often require specialized personnel, laboratory infrastructure, and extended testing time, limiting accessibility. This review critically examines recent innovations in the detection of olfactory dysfunction, focusing on portable, user-friendly smell test kits and their comparative performance with self-reported tools such as the Mini Olfactory Questionnaire (Self-MOQ) and 4-CAST. We synthesize evidence on diagnostic reliability, usability, and cultural adaptability, evaluating how these methods align with emerging needs in Alzheimer's and dementia research. </p><p> Portable kits such as PT-Smell and SSomix demonstrate high diagnostic precision and cultural adaptability, while self-administered and self-report tools enable scalable deployment in memory clinics and community screening programs. Within Alzheimer's research, these approaches present practical solutions for early identification of sensory biomarkers linked to cognitive decline. </p><p> To optimize diagnostic integration, a two-step framework is proposed: first-line screening with self-administered tools such as Self-MOQ or 4-CAST, followed by confirmatory psychophysical testing with portable kits such as PT-Smell or SSomix. This tiered model supports early AD and MCI detection, enhances accessibility, and promotes digital health integration for widespread olfactory monitoring. </p>.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Diagnosis of Alzheimer's: Machine Learning Analysis Leveraging Structural MRI.","authors":"Suhail Ahmad Dar, Nasheed Imtiaz, Rameez Ahmad Dar","doi":"10.2174/0115672050421991260125153049","DOIUrl":"https://doi.org/10.2174/0115672050421991260125153049","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Alzheimer's disease (AD) is characterized by significant brain atrophy, detectable via structural MRI. There has been less focus on cortical degeneration in subcortical regional deterioration-particularly during the transition from Mild Cognitive Impairment (MCI) to AD-which remains underexplored. This study aims to identify subcortical regions with progressive atrophy using surface-based morphometry (SBM) and evaluate their potential for early AD diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This longitudinal study collected data from MCI patients (6 months) who later progressed to Alzheimer's within 3 years, alongside healthy controls followed across four time points (6 months-3 years). Reported in line with STARD guidelines, the study aimed to evaluate model performance in distinguishing progressive MCI-to-AD from healthy controls to advance early Alzheimer's diagnosis. The study leveraged the ADNI dataset to analyse 68 subcortical regions in MCI-to-AD converters (MCI-AD) and Healthy Controls (HC) over 6 months to 3 years (i.e., at 6 months, 1 year, 2 years, and 3 years). The groups were classified beforehand using the Clinical Dementia Rating and the Mini-Mental Status Examination scores. Accordingly, three surfacebased morphometry (SBM) metrics-cortical thickness (CTh), gyrification index (GI), and sulcal depth (SD)-were evaluated in the progressive MCI group (individuals with MCI who later converted to Alzheimer's disease) as well as in healthy controls, to quantify morphological changes. Finally, the morphological data were utilized to train and test machine learning models for classification and prediction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Cortical regions exhibiting significant atrophy were identified using paired-samples ttests between 6 months and 3 years. In parallel, machine learning (ML) models were trained and tested on the same dataset to differentiate progressive MCI-to-AD cases from healthy controls across multiple time points (6 months, 1 year, 2 years, and 3 years), and subsequently to predict the progression to Alzheimer's disease. Certain evaluation metrics were considered for the classifier performance, i.e., Accuracy, F1-score, and AUC-ROC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Sub-cortical SBM metrics, particularly CTh, are sensitive to early AD-related atrophy, offering potential biomarkers for disease progression. ML models trained on these features enable accurate classification, with performance peaking near diagnosis-highlighting their utility in early intervention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;SBM-derived subcortical atrophy patterns aid early AD detection and, when combined with ML, offer a scalable predictive framework. Among metrics, CTh showed the greatest decline in MCI-AD, followed by SD and GI. Progressive deterioration was observed in specific subcortical regions, accelerating near diagnosis. Classifiers achieved higher accuracy in distinguishing MCI-AD from HC at later time ","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PREFACE.","authors":"Thomas van Groen","doi":"10.2174/0115672050468468260128100916","DOIUrl":"https://doi.org/10.2174/0115672050468468260128100916","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Microstructural MRI of Neuroinflammation in Alzheimer's Disease.","authors":"Banafsheh Baniasadipour, Fariba Bagheri, Farzane Hendudari, Soheila Koopaee, Seyed Mohammad Amini, Mahdieh Ahmadi Kamalabadi, Asieh Fatemidokht","doi":"10.2174/0115672050420458251115070244","DOIUrl":"https://doi.org/10.2174/0115672050420458251115070244","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a leading cause of cognitive decline in older adults, often diagnosed late when pathology and symptoms are established, reducing treatment effectiveness. Both AD and mild cognitive impairment (MCI) trigger neuroinflammation, leading to molecular and microstructural changes, including oxidative stress, mitochondrial dysfunction, glial activation, synaptic and neurotransmitter disturbances, myelin degradation, and white matter dysfunction. The blood-brain barrier (BBB) is also compromised.</p><p><strong>Methods: </strong>Advanced magnetic resonance imaging (MRI) techniques, such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), magnetization- transfer imaging (MTI), chemical exchange saturation transfer (CEST), contrast-enhanced MRI (CE-MRI), and arterial spin labeling (ASL), offer promise for the early detection of Alzheimer's disease (AD)-related molecular and microstructural changes.</p><p><strong>Results: </strong>Based on recent studies, advanced MRI modalities-including magnetic resonance spectroscopy, diffusion imaging, contrast-enhanced imaging, and chemical shift imaging-can highlight metabolic dysfunction, white matter degradation, microstructural disruption, blood-brain barrier dysfunction, cerebral hypoperfusion, vascular dysfunction, and pH alterations caused by neuroinflammation in Alzheimer's patients.</p><p><strong>Discussion: </strong>The integration of advanced MRI modalities into clinical practice could improve the diagnosis and management of Alzheimer's disease (AD). Magnetic resonance spectroscopy and diffusion imaging can identify metabolic and microstructural changes years before brain atrophy occurs, aiding professionals in the early detection of AD. Additionally, perfusion imaging and magnetization transfer imaging can help distinguish between Alzheimer's disease, frontotemporal dementia (FTD), and vascular dementia. Finally, contrast-enhanced MRI can monitor the integrity of the blood-brain barrier to evaluate responses to drug treatments.</p><p><strong>Conclusion: </strong>Despite challenges, such as longer scan times and limited specificity, advanced MRIbased approaches are at the forefront of identifying reliable biomarkers for early detection of Alzheimer's disease and determining optimal management and treatment strategies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Medication Factors Associated with Cognitive Decline in Dementia: A Healthcare Database Study.","authors":"Chen-Chih Chung, Jia-Hung Chen, Lung Chan, Hung-Yi Liu, Joni Yu-Hsuan Shao, Yi-Chieh Hung, Chien-Tai Hong","doi":"10.2174/0115672050420540251027112136","DOIUrl":"https://doi.org/10.2174/0115672050420540251027112136","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.","authors":"Akshay Thakur, Kaunava Roy Chowdhury, Ankush Kumar, Vir Vikram Sharma, Rohit Bhatia","doi":"10.2174/0115672050421604251108045622","DOIUrl":"https://doi.org/10.2174/0115672050421604251108045622","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Nose-to-Brain Delivery Systems for Effective Alzheimer's Disease Management.","authors":"Alka Sahu, Khileshwari, Kavita Patle, Parag Jain, Ajazuddin","doi":"10.2174/0115672050395356251106100427","DOIUrl":"https://doi.org/10.2174/0115672050395356251106100427","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effects Between Neurodegenerative Diseases, Metabolites, and Brain Volume.","authors":"Hengjian Liu, Sarah Hescham, Hans Clusmann, Yasin Temel, Dennis van der Meer","doi":"10.2174/0115672050413060251107021634","DOIUrl":"https://doi.org/10.2174/0115672050413060251107021634","url":null,"abstract":"<p><strong>Introduction/objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vagus Nerve Stimulation in the Management of Neurodegenerative Diseases: A Systematic Review of Advances in Animal Research and Clinical Applications.","authors":"Brandon Edelbach, Lei Huang, Warren Boling","doi":"10.2174/0115672050373772251103053036","DOIUrl":"https://doi.org/10.2174/0115672050373772251103053036","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}