Neurodegenerative Diseases最新文献

{"title":"Lithium: An Old Drug for New Therapeutic Strategy for Alzheimer's Disease and Related Dementia.","authors":"Seong Sool Shim, Ken Berglund, Shan Ping Yu","doi":"10.1159/000533797","DOIUrl":"10.1159/000533797","url":null,"abstract":"<p><strong>Background: </strong>Although Alzheimer's disease (AD) is the most common form of dementia, the effective treatment of AD is not available currently. Multiple trials of drugs, which were developed based on the amyloid hypothesis of AD, have not been highly successful to improve cognitive and other symptoms in AD patients, suggesting that it is necessary to explore additional and alternative approaches for the disease-modifying treatment of AD. The diverse lines of evidence have revealed that lithium reduces amyloid and tau pathology, attenuates neuronal loss, enhances synaptic plasticity, and improves cognitive function. Clinical studies have shown that lithium reduces the risk of AD and deters the progress of mild cognitive impairment and early AD.</p><p><strong>Summary: </strong>Our recent study has revealed that lithium stabilizes disruptive calcium homeostasis, and subsequently, attenuates the downstream neuropathogenic processes of AD. Through these therapeutic actions, lithium produces therapeutic effects on AD with potential to modify the disease process. This review critically analyzed the preclinical and clinical studies for the therapeutic effects of lithium on AD. We suggest that disruptive calcium homeostasis is likely to be the early neuropathological mechanism of AD, and the stabilization of disruptive calcium homeostasis by lithium would be associated with its therapeutic effects on neuropathology and cognitive deficits in AD.</p><p><strong>Key messages: </strong>Lithium is likely to be efficacious for AD as a disease-modifying drug by acting on multiple neuropathological targets including disruptive calcium homeostasis.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154771","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":"Predicting the Rapid Progression of Mild Cognitive Impairment by Intestinal Flora and Blood Indicators through Machine Learning Method.","authors":"Lingling Wang, Jing Yan, Huiqin Liu, Xiaohui Zhao, Haihan Song, Juan Yang","doi":"10.1159/000538023","DOIUrl":"10.1159/000538023","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the work was to establish a prediction model of mild cognitive impairment (MCI) progression based on intestinal flora by machine learning method.</p><p><strong>Method: </strong>A total of 1,013 patients were recruited, in which 87 patients with MCI finished a two-year follow-up. To establish a prediction model, 61 patients were randomly divided into a training set and 26 patients were divided into a testing set. A total of 121 features including demographic characteristics, hematological indicators, and intestinal flora abundance were analyzed.</p><p><strong>Results: </strong>Of the 87 patients who finished a two-year follow-up, 44 presented rapid progression. Model 1 was established based on 121 features with the accuracy 85%, sensitivity 85%, and specificity 83%. Model 2 was based on the first fifteen features of model 1 (triglyceride, uric acid, alanine transaminase, F-Clostridiaceae, G-Megamonas, S-Megamonas, G-Shigella, G-Shigella, S-Shigella, average hemoglobin concentration, G-Alistipes, S-Collinsella, median cell count, average hemoglobin volume, low-density lipoprotein), with the accuracy 97%, sensitivity 92%, and specificity 100%. Model 3 was based on the first ten features of model 1, with the accuracy 97%, sensitivity 86%, and specificity 100%. Other models based on the demographic characteristics, hematological indicators, or intestinal flora abundance features presented lower sensitivity and specificity.</p><p><strong>Conclusion: </strong>The 15 features (including intestinal flora abundance) could establish an effective model for predicting rapid MCI progression.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"43-52"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990706","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":"A Paradigm Shift in the Management of Patients with Parkinson's Disease.","authors":"Konstantinos I Tsamis, Per Odin, Angelo Antonini, Heinz Reichmann, Spyridon Konitsiotis","doi":"10.1159/000533798","DOIUrl":"10.1159/000533798","url":null,"abstract":"<p><strong>Background: </strong>Technological evolution leads to the constant enhancement of monitoring systems and recording symptoms of diverse disorders.</p><p><strong>Summary: </strong>For Parkinson's disease, wearable devices empowered with machine learning analysis are the main modules for objective measurements. Software and hardware improvements have led to the development of reliable systems that can detect symptoms accurately and be implicated in the follow-up and treatment decisions.</p><p><strong>Key messages: </strong>Among many different devices developed so far, the most promising ones are those that can record symptoms from all extremities and the trunk, in the home environment during the activities of daily living, assess gait impairment accurately, and be suitable for a long-term follow-up of the patients. Such wearable systems pave the way for a paradigm shift in the management of patients with Parkinson's disease.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"13-19"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425415","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":"Cerebral Tau Deposition in Comorbid Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis: An [18F]-Flortaucipir and 7T MRI Study.","authors":"Ian Cheong, Yong Du, Gwenn Smith, Jun Hua, Xu Li, Alexander Pantelyat","doi":"10.1159/000536614","DOIUrl":"10.1159/000536614","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS).</p><p><strong>Method: </strong>[18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson's syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively.</p><p><strong>Results: </strong>In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions.</p><p><strong>Conclusion: </strong>In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"35-42"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288635","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":"Epidemiological Impact of Neurodegenerative Diseases in the Rural Spanish-Portuguese Cross-Border Region.","authors":"Montserrat Alonso-Sardón, Manuel Paulino, Adília Fernandes, María Antonia Martín-Delgado, Raixa Noemí Pérez-Martín, Carlos Pires Magalhães, Helena Pimentel, Augusta Mata, Justina Silvano, Agostinha Corte, Teresa Paiva, Ermelinda Marques","doi":"10.1159/000535683","DOIUrl":"10.1159/000535683","url":null,"abstract":"<p><strong>Introduction: </strong>Epidemiological data indicate that neurodegenerative diseases show a high prevalence with a progressive increasing trend, especially in aging populations, as is the case in rural areas. The objective of this study was to assess the quantitative impact of neurodegenerative diseases in rural areas of the Spanish-Portuguese border region and to describe the epidemiological profile of the most prevalent disorders in one of the most depopulated and aged regions of Europe.</p><p><strong>Methods: </strong>A cross-sectional descriptive study was designed to estimate the prevalence of subjects diagnosed with the most common neurodegenerative disorders: dementia (Alzheimer's disease and other dementias), Parkinson's disease and Parkinsonism, and multiple sclerosis in the Spanish-Portuguese cross-border border region in 2020. It includes Bragança and Guarda Districts (Portugal) and Salamanca (Castilla y León, Spain).</p><p><strong>Results: </strong>Neurodegenerative diseases accounted for 1.85% in the Spanish-Portuguese cross-border region in 2020; a total of 5,819 records were reported: 987 (prevalence, 2.51%) in Salamanca (Spain); 2,332 (prevalence, 1.87%) in Bragança; and 2,500 (prevalence, 1.66%) in Guarda. Female population suffered from them in higher proportion (2.35 vs. 1.32%). Dementia represented 1.19% (3,744), Parkinson's disease and Parkinsonism 0.58% (1,823), and multiple sclerosis 0.08% (252). These disorders impacted older age groups. In the rural border region of Spain, 1 out of 4 cases were institutionalized.</p><p><strong>Conclusion: </strong>The findings reveal the health impact of neurodegenerative diseases in the Spanish-Portuguese cross-border region. The epidemiological data emphasize the region's circumstances and highlight research priorities. Intervention strategies must be implemented in the region to ensure quality healthcare in rural areas.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"25-34"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830740","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":"Neuroimaging and Neurodegeneration.","authors":"Daniele Botta, Karl-Olof Lövblad","doi":"10.1159/000536438","DOIUrl":"10.1159/000536438","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"53-55"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723481","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":"Verbal Learning Impairment in Parkinson's Disease: Role of the Frontostriatal System in Working and Strategic Memory.","authors":"Alessandro Cocuzza, Teresa Difonzo, Edoardo Nicolò Aiello, Luca Pietro Ernesto Sbrissa, Stefano Zago, Claudia Gendarini, Martina Andrea Sirtori, Barbara Poletti, Nicola Ticozzi, Giulia Franco, Alessio Di Fonzo, Giacomo Pietro Comi, Maria Cristina Saetti","doi":"10.1159/000534307","DOIUrl":"10.1159/000534307","url":null,"abstract":"<p><strong>Introduction: </strong>Learning is a long-term memory process, influenced by working memory control processes, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of the study was to investigate the verbal learning strategies of individuals with Parkinson's disease (PD).</p><p><strong>Methods: </strong>Thirty individuals with idiopathic PD and healthy control (HC) subjects were tested with a multi-trial word list learning, under two conditions: without cue and then with an explicit cue suggesting the categories in the list, respectively.</p><p><strong>Results: </strong>In comparison to HC subjects, individuals with PD recalled fewer words and achieved a reduced number of categorical clusters; the strategical cue did not improve their performance.</p><p><strong>Conclusion: </strong>This suggests, besides a difficulty in identifying the correct learning strategy, a deficit in working memory, which undermines the strategy implementation.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"20-24"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138016","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":"Contents Vol. 21, 2021","authors":"","doi":"10.1159/000525982","DOIUrl":"https://doi.org/10.1159/000525982","url":null,"abstract":"<br />Neurodegener Dis 2021;21:I–VI","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138509449","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":"Acknowledgement to Reviewers","authors":"","doi":"10.1159/000525916","DOIUrl":"https://doi.org/10.1159/000525916","url":null,"abstract":"<br />Neurodegener Dis 2021;21:150","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 10","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138509459","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":"Juvenile-Onset Kufs Disease in a Chinese Consanguineous Family due to CLN6 Mutation","authors":"Weimin Jia, Yalin Luo, Jiuxiang Wang, Yue Yang, Wenming Yang, Xianqin Zhang","doi":"10.1159/000524784","DOIUrl":"https://doi.org/10.1159/000524784","url":null,"abstract":"Objective: The aim of this study was to identify the genetic cause of two cases of Kufs disease in the same family. The two affected individuals exhibited different levels of severity under magnetic resonance imaging (MRI). Methods: Whole-exome sequencing was performed on affected individuals, and the candidate gene was confirmed by Sanger sequencing. Western blot analysis was used to evaluate the level of expression of CLN6 protein in 239T cells. Results: We identified a novel homozygous mutation of the CLN6 gene (c.14G>T, p.Arg5Leu) in a consanguineous Chinese family in which two people had Kufs disease. Both patients exhibited seizures and progressive psychomotor decline and mental deterioration without visual impairment. They had different ages of onset, although they carried the same missense mutation. The affected female showed a pronounced abnormal MRI signal in the bilateral hippocampus, while her younger brother only showed a very slight abnormal signal. Further study showed that this missense mutation could decrease the level of expression of CLN6 protein. Conclusions: A novel homozygous mutation of the CLN6 gene was identified, and patients with the same mutation showed different ages of onset and different levels of severity under MRI. Significance: Our study established that the same CLN6 mutation could produce different phenotypes in patients, and it has expanded the mutational and phenotypical spectrum of the CLN6 gene.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":"126 - 131"},"PeriodicalIF":3.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48590932","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}