Neurodegenerative Diseases最新文献

{"title":"Sex Differences in Biofluid Biomarkers for Alzheimer's Disease.","authors":"Mari Aksnes, Mari Aksnes","doi":"10.1159/000545717","DOIUrl":"10.1159/000545717","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), the most common cause of dementia, affects twice as many women as men. Moreover, sex is increasingly recognised as an important factor for AD, influencing symptom presentation, progression, disease biology, and treatment responses. In parallel, AD biomarkers are becoming more accessible with the discovery of specific and accurate blood-based biomarkers and their incorporation in AD diagnostic frameworks. This narrative review aimed to summarise sex differences in the concentration and interpretation of biofluid biomarkers for AD.</p><p><strong>Summary: </strong>Biological sex may influence both the concentration and interpretation of biofluid biomarkers for AD pathology such as amyloid-β aggregation, tau neurofibrillary tangles, neurodegeneration, or neuroinflammation. While some biofluid biomarkers display consistent sex differences in absolute levels, most biomarker levels have not been found to differ consistently by sex. Nonetheless, even biomarkers that do not differ in absolute levels display sex-specific associations with clinically relevant variables such as brain atrophy, cognitive impairment, and disease progression.</p><p><strong>Key message: </strong>Sex may influence the interpretation of AD biomarkers depending on their context of use, and more research is required to develop sex-specific guidelines. Future research should aim to study sex differences and sex-specific associations with variables of interest, as well as the underlying factors driving sex differences in AD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"134-144"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Glymphatic System in Cerebrospinal Fluid Dynamics: Clinical Implications, Its Evaluation, and Application to Therapeutics.","authors":"Masahiro Ohara, Takaaki Hattori","doi":"10.1159/000546286","DOIUrl":"10.1159/000546286","url":null,"abstract":"<p><strong>Background: </strong>The glymphatic system is a waste clearance system that facilitates the efficient removal of interstitial solutes, including neurotoxic substances such as β-amyloid, from the central nervous system. Numerous studies have highlighted its pivotal role in the pathophysiology of neurodegenerative diseases and cerebrospinal fluid (CSF) disorders. A comprehensive understanding and accurate evaluation of the glymphatic system are of significant clinical importance. Furthermore, emerging evidence suggests that modulating glymphatic activity holds therapeutic potential, including enhancing drug delivery across the brain.</p><p><strong>Summary: </strong>This review consolidates current insights into the glymphatic system, addressing areas of consensus as well as ongoing controversies. The relationship between glymphatic dysfunction and CSF disorders is discussed, alongside advancements in evaluation methodologies. Additionally, therapeutic applications of glymphatic modulation are summarized, particularly its role in optimizing drug distribution within the brain.</p><p><strong>Key messages: </strong>This review provides a comprehensive overview of the current knowledge on the glymphatic system and highlights imaging techniques used to assess human glymphatic function, including magnetic resonance imaging (MRI) with contrast agents, diffusion tensor imaging, and emerging techniques such as MRI with 17O-labeled water. Furthermore, the therapeutic implications of glymphatic modulation are discussed, and directions for future research are proposed.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"189-201"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Developing Alzheimer Disease in Relation to Common Infections.","authors":"Alejandra Camacho-Soto, Irene Faust, Osvaldo J Laurido-Soto, Jordan A Killion, Natalie Senini, Brittany Krzyzanowski, Brad A Racette","doi":"10.1159/000546589","DOIUrl":"10.1159/000546589","url":null,"abstract":"<p><strong>Introduction: </strong>Many studies demonstrate positive associations between infections and Alzheimer disease (AD), suggesting that brain and/or systemic inflammation may impact AD pathogenesis. However, studies of meningitis and AD risk have been limited to animal models or small human cohorts in the USA. The objective of this study was to examine the relationship between incident AD and three different types of infections (meningitis, pneumonia, and urinary tract infections [UTIs]) using a population-based sample of US Medicare beneficiaries.</p><p><strong>Methods: </strong>We created a case-control dataset by frequency matching 4:1 (control:case) by age group, sex, and month/year of the date of AD diagnosis or control selection date. We identified 52,628 newly diagnosed AD cases and 210,512 population-based controls ≥67 years of age using comprehensive Medicare claims data from 2016 to 2018. We classified infections using ICD-9-CM and ICD-10-CM diagnosis codes. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between AD and each infection separately. We lagged exposures up to 18 months and examined hospitalization or comorbid sepsis as a proxy for infection severity. Covariates included age, sex, race/ethnicity, and health care utilization.</p><p><strong>Results: </strong>AD was positively associated with meningitis in individuals hospitalized without superimposed sepsis with a 6-month lag (OR = 2.713, 95% CI: 1.277-5.764), and UTIs without superimposed sepsis with an 18-month lag (OR = 1.231, 95% CI: 1.101-1.376), and with superimposed sepsis with an 18-month lag (OR = 1.388, 95% CI: 1.050-1.835). There was no association between AD and pneumonia in individuals hospitalized with or without superimposed sepsis. When examining infections that occurred in the outpatient setting, the association between AD and UTI remained positive yet attenuated at all time points, however, the association became inverse between AD and pneumonia.</p><p><strong>Conclusion: </strong>More severe infections, particularly meningitis, may be associated with a higher risk of AD, due to either unmasking of prodromal AD or acceleration of AD pathogenesis in susceptible individuals.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"180-188"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Amyloid Treatments: A Therapeutic Revolution, Ready for Europe.","authors":"Paolo Salvioni Chiabotti, Paolo Salvioni Chiabotti, Giulia Bommarito, Patrik Michel, Beatrice Pizzarotti, Fabrizio Piazza, Federica Agosta, Ralf J Jox, Simon Wieser, Philippe Ryvlin, Giovanni B Frisoni, Bruno Dubois, Olivier Rouaud, Gilles Allali","doi":"10.1159/000545800","DOIUrl":"10.1159/000545800","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"107-113"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's Disease, β-Amyloid Peptides, and Ubiquitin-Proteasome System: Nutritherapeutic Insights.","authors":"Philippe Yves Rémy Simon, Renaud David","doi":"10.1159/000545170","DOIUrl":"10.1159/000545170","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease - an age-related neurodegenerative disorder leading to progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble β-amyloid (Aβ) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aβ oligomers - a central dysfunction in the etiology of the disease.</p><p><strong>Summary: </strong>The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment. In particular, the potential for synergistic strategies combining diet-derived proteasome activators, immunoproteasome inhibitors, and modulators of Aβ peptide aggregation to prevent, delay or even reverse disease progression over time is currently arousing growing interest.</p><p><strong>Key messages: </strong>From that perspective, and in light of the recent advances in the understanding of the key molecular and cellular mechanisms underlying Alzheimer's disease pathogenesis, the present review highlights the mechanisms of action and the preventive and therapeutic potential of some diet-derived bioactive compounds and other natural substances of interest. This article is a translated, updated, and expanded version of an article originally published in French in Médecine/Sciences, August/September 2023 (https://doi.org/10.1051/medsci/2023094).</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"76-87"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Neuromuscular Ultrasound in Patients with Amyotrophic Lateral Sclerosis.","authors":"Jieying Wu, Hongsong Song, Mukadas Arkin, Shuo Zhang, Xiao Huang, Dongsheng Fan, Yingsheng Xu","doi":"10.1159/000546425","DOIUrl":"10.1159/000546425","url":null,"abstract":"<p><strong>Introduction: </strong>Neuromuscular ultrasound has been increasingly used in the detection and diagnosis of amyotrophic lateral sclerosis (ALS), commonly characterized by peripheral nerve atrophy, degeneration, and muscle fasciculations. The aim of this study was to assess the ultrasound characteristics of ALS patients.</p><p><strong>Methods: </strong>A total of 67 consecutive patients with sporadic ALS and 19 with ALS mimics (63.16% peripheral neuropathy) were recruited. Ultrasound and electrophysiological examinations were performed; the peripheral nerve cross-sectional area (CSA) and fasciculation grades were compared between the groups, and correlations between ultrasound and electrophysiological data in ALS patients were determined.</p><p><strong>Results: </strong>ALS patients had smaller proximal median and ulnar nerve CSAs than those of ALS mimics, who exhibited asymmetric changes. Fasciculation differences in the trapezius, triceps brachii, extensor digitorum communis, thenar, and first dorsal interosseous muscles were observed. In ALS patients, the CSA and fasciculation relative scores were correlated with electrophysiological indicators.</p><p><strong>Conclusion: </strong>Ultrasound is a valuable tool for monitoring peripheral nerve CSA and muscle fasciculations, both of which correlate with electrophysiological indices, in ALS patients.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"169-179"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Sex Differences in Neurodegeneration and Psychological Comorbidities in Multiple Sclerosis and Related Disorders.","authors":"Jelena Brasanac, Josephine Heine, Claudia Chien","doi":"10.1159/000544813","DOIUrl":"10.1159/000544813","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic neuroinflammatory conditions that disproportionately affect women, with a 2:1 ratio in MS and up to 8.9:1 in NMOSD. Cognitive impairment is one of the earliest and most debilitating symptoms of MS, while mood disorders are common and significantly impact the quality of life and disease prognosis. Understanding sex differences in disease progression, particularly the potential differences in the mechanisms behind disability, is critical for advancing patient care.</p><p><strong>Summary: </strong>This review synthesizes current knowledge of sex-specific differences in MS and NMOSD, with a focus on neuroinflammation and neurodegeneration, as well as cognitive symptoms, and psychiatric comorbidities. The current state of research highlights the role of hormonal changes over the patient's lifespan, such as estrogen and testosterone, as well as their role in modulating neuroinflammatory responses and subsequent neurodegeneration.</p><p><strong>Key messages: </strong>Sex differences research in MS and NMOSD is scarce. Here, we discuss implications of disease monitoring and furthering knowledge in the field with a sex-specific lens, including recommendations for evaluating sex differences and personalized care in MS and NMOSD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"21-35"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huntington's Disease in Hospitalized Patients Infected with SARS-CoV-2 in Brazil: Three-Year Update.","authors":"Jéssica Paula Martins, Juliana Mozer Sciani, Fernando Augusto Lima Marson","doi":"10.1159/000538170","DOIUrl":"10.1159/000538170","url":null,"abstract":"<p><strong>Introduction: </strong>Huntington's disease (HD) is considered a rare and fatal neurodegenerative disease; despite that, only one study has described the outcomes among individuals with HD and COVID-19. In this context, an epidemiological investigation was conducted in Brazil using data from Open-Data-SUS (<ext-link ext-link-type=\"uri\" xlink:href=\"https://opendatasus.saude.gov.br/\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">https://opendatasus.saude.gov.br/</ext-link>), a Brazilian open dataset encompassing demographic and clinical information of hospitalized patients.</p><p><strong>Method: </strong>The study comprised 2,180,403 hospitalized patients due to COVID-19 in Brazil from December 29, 2019, to April 6, 2023. From the total original database, patients with HD and three control groups were selected (control 1 [CG-1] - hospitalized patients with COVID-19 and a neurological disorder [except those with HD], control 2 [CG-2] - hospitalized patients with COVID-19 and no comorbidities, and control 3 [CG-3] - hospitalized patients with COVID-19 except for those with HD). The study described the following characteristics of these patients: sex, age, race, place of residence, presence of nosocomial infection, clinical signs, comorbidities, use of antiviral medication for the flu, need for intensive care unit, need for mechanical ventilation support, discharge criteria, and outcome.</p><p><strong>Results: </strong>A total of 60 patients with HD were enrolled, representing a prevalence of 2.8 per 100,000 inhabitants. Of these, 23 were men, 30 were aged between 25 and 60 years, 38 were White, 58 lived in urban areas, and two had a nosocomial infection. The main clinical signs presented were fever (N = 45), dyspnea (N = 45), peripheral oxygen saturation <95% (N = 45), cough (N = 38), and respiratory discomfort (N = 37). The main comorbidities were cardiopathy (N = 13), asthma (N = 2), and chronic lung disease (N = 2). Four patients received antiviral medication for the flu. During hospitalization, 18 patients required admission to an intensive care unit, 10 used invasive mechanical ventilation, 42 used noninvasive mechanical ventilation, and eight did not use ventilatory support. Regarding outcomes, 36 patients were cured, 23 died due to COVID-19, and 1 died from a cause not associated with COVID-19. In the comparison of markers between patients with HD and the controls, the following significant associations were described: (CG-1) patients with HD were younger and presented fewer clinical signs and comorbidities; (CG-2) patients with HD were commonly female, older, presented fewer clinical signs, and had a higher chance of death (OR = 2.354 [95% CI = 1.395-3.973]); and (CG-3) patients with HD were more commonly female and presented fewer clinical signs and comorbidities.</p><p><strong>Conclusions: </strong>Patients with HD can be considered an at-risk population due to the poor clinical outcomes compared to patients without comorbidities. E","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"88-105"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluid and Waste Clearance in Central Nervous System Health and Diseases.","authors":"Marie-Renee El Kamouh, Marie-Renee El Kamouh, Stéphanie Lenck, Stéphane Lehericy, Helene Benveniste, Jean-Léon Thomas","doi":"10.1159/000546018","DOIUrl":"10.1159/000546018","url":null,"abstract":"<p><p><p>Background: In respect to the circulatory system, the central nervous system (CNS) differs from other organs in the body by three main features. First, the CNS is surrounded by a compartment filled with cerebrospinal fluid (CSF). Second, the CNS is devoid of lymphatic vessels, which are found in the dura mater of the meninges. Third, the CNS blood vasculature serves as a scaffold to perivascular spaces allowing CSF to circulate into the CNS parenchyma via the glymphatic system. Summary: This review highlights the contribution of the glymphatic system and meningeal lymphatic vasculature to CNS homeostasis and also recapitulates the alterations of glymphatic-meningeal lymphatic systems that have been associated to neurological disorders, especially neurodegenerative diseases. Key Message: We discuss the controversies and limitations in current research, emphasizing the need for cautious interpretation while highlighting the potential of glymphatic and meningeal lymphatic pathways as therapeutic targets in neurological disorders. </p>.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"145-166"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurology of Aging: Adapting Neurology Provision for an Aging Population.","authors":"Patrick Stancu, Lisa Hentsch, Margitta Seeck, Dina Zekry, Christophe Graf, Vanessa Fleury, Frédéric Assal","doi":"10.1159/000540972","DOIUrl":"10.1159/000540972","url":null,"abstract":"<p><strong>Background: </strong>Over the past few decades, advances in the neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research, and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise.</p><p><strong>Summary: </strong>Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric healthcare providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have not only helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage.</p><p><strong>Key messages: </strong>Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"14-20"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}