ABSTRACT
BACKGROUND: The physical function of elderly individuals reflects whether they have had a history of regular physical activity over the long term. Such indicators have been found to have a certain connection with cognitive function these years. However, there is limited research that associates it with mechanisms such as cerebral Aß deposition. We aim to investigate this relationship and unveil the underlying mechanisms. METHOD: Physical function and cognition data of 4189 participants were obtained from the Chinese preclinical Alzheimer's disease study. Participants were divided into six groups according to disease severity. Among them, 1048 participants underwent the positron emission tomography-computed tomography (PET-CT) and plasma biomarker test. Grip strength and gait were combined into a score indicating physical function. Multiple linear regression models and logistic regression models were mainly used to conduct the analysis. RESULTS: There was a significant positive correlation between physical function and cognitive function (R = 0.48, p < 0.001), independent of sex, age, apolipoprotein E-ε4 genotype, and disease stages (p < 0.001). Physical function was effective in distinguishing individuals with cognitive impairment from those without (AUC = 0.835). Physical function was negatively associated with brain Aß deposition (p = 0.008) and brain Aß had an intermediary effect (p < 0.01) on the association between physical function and cognition in women. This association was mainly evident in the lateral parietal, lateral temporal, posterior cingulate, frontal, occipital, and precuneus regions. Physical function was negatively associated with plasma neurofilament light-chain (Nfl) level (p < 0.001). CONCLUSIONS: Physical function is strongly associated with cognitive function in the Chinese elderly, and brain Aß deposition partly mediates the linkage in women. Plasma Nfl can be used as a potential target for exercise intervention in cognitive function. Improving physical function will contribute to the alleviation of cognition decline.
Subject(s)
Amyloid beta-Peptides , Biomarkers , Brain , Humans , Female , Male , Aged , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/metabolism , Biomarkers/blood , Brain/metabolism , Brain/diagnostic imaging , Asian People , Aged, 80 and over , Middle Aged , Cognition/physiology , Cognitive Dysfunction/blood , Positron Emission Tomography Computed Tomography , Hand Strength/physiology , China , Neurofilament Proteins/blood , East Asian PeopleABSTRACT
Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.
Subject(s)
Aging , Ammonia , Bile Acids and Salts , Cognitive Dysfunction , Intestinal Absorption , Animals , Bile Acids and Salts/metabolism , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Intestinal Absorption/drug effects , Male , Female , Humans , Mice , Aging/metabolism , Ammonia/metabolism , Aged , Mice, Inbred C57BL , Cholestyramine Resin/pharmacology , Symporters/metabolism , Organic Anion Transporters, Sodium-Dependent/metabolism , Organic Anion Transporters, Sodium-Dependent/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Hippocampus/metabolism , Hippocampus/pathology , Rats , Aged, 80 and overABSTRACT
The metabolic implications in Alzheimer's disease (AD) remain poorly understood. Here, we conducted a metabolomics study on a moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, and brain amyloid-ß deposition (n = 421). These features demonstrated synergistic performances across clinical stages and subpopulations and enhanced the differentiation of AD stages beyond demographics and Apolipoprotein E ε4 allele (APOE-ε4). We validated their performances in eight data sets (total n = 7685) obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Memory and Aging Project (ROSMAP). Importantly, identified features are linked to blood ammonia homeostasis. We further confirmed the elevated ammonia level through AD development (n = 1060). Our findings highlight AD as a metabolic disease and emphasize the metabolite-mediated ammonia disturbance in AD and its potential as a signature and therapeutic target for AD.
Subject(s)
Alzheimer Disease , Ammonia , Metabolomics , Phenotype , Humans , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Ammonia/metabolism , Aged , Female , Male , Middle Aged , Brain/metabolism , Brain/diagnostic imaging , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/genetics , Amyloid beta-Peptides/metabolism , Apolipoprotein E4/genetics , Apolipoprotein E4/metabolism , Bile Acids and Salts/metabolism , Aged, 80 and over , Cohort StudiesABSTRACT
OBJECTIVE: The study aims to investigate and visualize the hotspots of acupuncture for Allergic rhinitis (AR) over the past two decades and pinpoint future trends in this field. METHOD: We conducted a systematic search of English-language articles or reviews on acupuncture for AR in the Web of Science Core Collection from 2002 to 2022. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles. RESULT: The study identified 197 documents, 80 journals, 458 keywords, and 928 authors associated with acupuncture for AR. Although article publication fluctuated over the past 20 years, an overall upward trend emerged, with rapid growth during the second decade. China contributed the most to acupuncture research on AR and had the closest collaborations with the United States and Germany. China Medical University was the most prolific institution, and Benno Brinkhaus was the most productive and influential author. The most published journal was Medicine, while the Journal of Allergy and Clinical Immunology was the most frequently cited journal. The highest frequency keywords included acupuncture, allergic rhinitis, and asthma. Randomized controlled trials and alternative & complementary medicine remained significant research hotspots, while rhinoconjunctivitis is expected to be the emerging focus of future investigations. CONCLUSION: acupuncture has experienced robust development for the treatment of allergic rhinitis over the last two decades, with rhinoconjunctivitis and clinical research being the anticipated trends and frontiers of future research.
Subject(s)
Acupuncture Therapy , Asthma , Rhinitis, Allergic , Humans , Rhinitis, Allergic/therapy , Bibliometrics , ChinaABSTRACT
Background: A traumatic spinal cord injury (TSCI) can lead to severe nerve damage and disability. Cell transplantation therapy has shown great potential in the reconstruction of damaged spinal cords and promoting functional recovery. However, there is a lack of frontiers and futures analysis in the study of cell transplantation in TSCI. Methods: We used CiteSpace, VOSviewer and biblilometrix R package to perform bibliometric analysis on cell transplantation in TSCI from 2013 to 2023. Bibliometric records were extracted from English articles and reviews from the Web of Science core collection. Results: The bibliometric analysis included 284 papers published in 154 journals by 1,780 authors from 487 institutions in 41 countries and regions. The number of articles published in the past decade has fluctuated slightly, while the number of article citations has steadily increased. Mainland China and the United States are the leading countries and regions in this field, with the National Natural Science Foundation of China being the most funded foundation, and the United States being the country with the most funded articles. The University of Toronto in Canada is a prolific institution. Michael G. Fehlings has published the most articles, and D Michele Basso is the most cited author. Cell transplantation is the most published journal, and the Journal of Neurotrauma is the most cited journal. Cell and tissue engineering and clinical neurology are the basic disciplines in this field, and cutting-edge disciplines include developmental biology, biochemistry and molecular biology, and materials science and multidisciplinary. This study also helps scholars understand the current hotspots and future trends in this field. Marrow stromal cells, glial progenitor, and cell therapy are current research hotspots in this field, while nerve regeneration, cell therapy, and the safety of transplantation of transplantation may be potential research directions in the future. Conclusion: Cell transplantation after TSCI is receiving increasing attention. Cell therapy is both the frontier and a possible future trend in TSCI research. In addition, glial progenitor and marrow stromal cells are also current research hotspots. Meanwhile, nerve regeneration and safety of transplantation may be potential research directions. These findings will help further deepen research on cell transplantation for TSCI in scientific work.
ABSTRACT
Introduction: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, are heavy burdens to global health and economic development worldwide. Mounting evidence suggests that exercise, a type of non-invasive intervention, has a positive impact on the life quality of elderly with neurodegenerative diseases. X-omics are powerful tools for mapping global biochemical changes in disease and treatment. Method: Three major databases were searched related to current studies in exercise intervention on neurodegenerative diseases using omics tools, including metabolomics, metagenomics, genomics, transcriptomics, and proteomics. Result: We summarized the omics features and potential mechanisms associated with exercise and neurodegenerative diseases in the current studies. Three main mechanisms by which exercise affects neurodegenerative diseases were summed up, including adult neurogenesis, brain-derived neurotrophic factor (BDNF) signaling, and short-chain fatty acids (SCFAs) metabolism. Conclusion: Overall, there is compelling evidence that exercise intervention is a feasible way of preventing the onset and alleviating the severity of neurodegenerative diseases. These studies highlight the importance of exercise as a complementary approach to the treatment and intervention of neurodegenerative diseases in addition to traditional treatments. More mechanisms on exercise interventions for neurodegenerative diseases, the specification of exercise prescriptions, and differentiated exercise programs should be explored so that they can actually be applied to the clinic.
ABSTRACT
Acupuncture is an alternative therapy for Parkinson's disease (PD), but its efficacy and safety are controversial. Our previous study, which reviewed the literature from 1974 to 2012, could not find enough evidence from rigorously designed randomized, controlled trials (RCTs) to make a conclusion about the efficacy of acupuncture. Recently, more RCTs and meta-analyses have been conducted to evaluate the efficacy of acupuncture. The aim of our current study is to provide updated information in brief on this topic. In this study, we analyzed and summarized seven RCTs and four meta-analyses. Although all included studies were not of high quality, we found that there has been a tremendous progress in acupuncture research in treating Parkinson's disease (PD) during the past 5 years, based on our experience and insights into the behavioral assessments of PD. First, the numbers of RCTs and meta-analyses based on RCTs are increasing. Second, non-motor symptoms are increasingly emphasized. Third, objective behavioral assessment tools are being employed. Although recent studies can provide limited evidence for the efficacy of acupuncture, we make the following recommendations for the future investigation: First, large, multicenter, well-designed RCTs should be organized for evaluation of the efficacy of acupuncture. Second, objective assessments using novel computerized technologies should be considered. Third, target symptoms should be selected and evaluated instead of only performing global evaluations. Fourth, attention should be paid to the efficacy of scalp acupuncture. Fifth, the safety of acupuncture should be evaluated and reported.