Frontiers in Aging Neuroscience最新文献

Objective: The diagnosis and treatment of biomarkers in Alzheimer's disease has emerged as a prominent topic within Alzheimer's disease research. In this paper, we conducted a bibliometric analysis of data from a wide range of literature in this field to enhance the in-depth understanding of this area.

Method: The core collection of the Science Citation Index database (web of science) was used to search for relevant literature in the above fields from 1 January 2006 to 14 November 2022 and Citespace software was used to visualize and analyze the literature data.

Results: A total of 1,138 papers were included, of which the United States ranked first with 607 papers and China ranked 6th in the world with 84 papers. The value of mediational centrality is 0.49 in the United States and 0.05 in China. In terms of the number of articles published by the research authors, the Swedish scholar Blennow Kaj ranks first with 82 articles published, and the scholars who rank second and third are Zetterberg Henrik (78 articles) and Morris John C (64 articles), respectively; in terms of the mediational centrality, the American scholar Trojanowski John Q ranked first in the world with 0.1, and the second and third ranked scholars were Blennow Kaj (0.09) and Zetterberg Henrik (0.06) respectively. Scholar JACK CR ranked first with 377 citation frequency. The journal NEUROLOGY is ranked first with 943 citations.

Conclusion: In recent years, global research in the field of biomarkers related to Alzheimer's disease has shown signs of softening, and the momentum of research has slightly diminished. However, this trend does not imply a decline in the quality of research. It is essential to enhance collaboration among countries, major research institutions, and scholars, with a particular emphasis on fostering international partnerships in the future.

Objective: Cerebrospinal fluid biomarkers are challenging to use for diagnosing mild cognitive impairment (MCI) in large populations, and there is an urgent need for new blood biomarkers. The aim of this study is to investigate whether astrocyte activation is correlated with hippocampal atrophy, and to assess the potential of glial fibrillary acidic protein (GFAP) as a biomarker for diagnosing MCI among community-dwelling older individuals.

Methods: This cross-sectional study included 107 older adults. The levels of GFAP in serum were measured, and the volumetric assessment of gray matter within hippocampal subregions was conducted using Voxel-Based Morphometry (VBM). The relationship between hippocampal subregion volume and blood biomarkers were analyzed using partial correlation. The effectiveness of blood biomarkers in differentiating MCI was assessed using a receiver operating characteristic (ROC) curve.

Results: We found that serum GFAP levels were significantly elevated in the MCI group compared to the cognitively normal (CN) group. Additionally, individuals with MCI exhibited a reduction gray matter volume in specific hippocampal subregions. Notably, the right dentate gyrus (DG) and right cornu ammonis (CA) subregions were found to be effective for distinguishing MCI patients from CN individuals. Serum levels of GFAP demonstrate a sensitivity of 65.9% and a specificity of 75.6% in differentiating patients with MCI from CN individuals.

Conclusion: Specific atrophy within hippocampal subregions has been observed in the brains of community-dwelling elderly individuals. Elevated levels of circulating GFAP may serve as a sensitive peripheral biomarker indicative of hippocampal-specific cognitive alterations in patients with MCI.

Dementia encompasses a spectrum of neurodegenerative disorders significantly impacting global health, with environmental factors increasingly recognized as crucial in their etiology. Among these, ozone, has been identified as a potential exacerbator of neurodegenerative processes, particularly in Alzheimer's disease (AD). Ozone exposure induces the production of reactive oxygen species (ROS), which penetrate the BBB, leading to oxidative damage in neuronal cells. This oxidative stress is closely linked with mitochondrial dysfunction and lipid peroxidation, processes that are foundational to the pathology observed in dementia, such as neuronal death and protein aggregation. Furthermore, ozone triggers chronic neuroinflammation, exacerbating these neurodegenerative processes and perpetuating a cycle of CNS damage. Recent studies highlight the role of peripheral biomarkers like High Mobility Group Box 1 (HMGB1) and Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in mediating ozone's effects. Disruption of these and other identified proteins by ozone exposure impairs microglial function and response to amyloid plaques, suggesting a novel pathway through which ozone may influence AD pathology via immune dysregulation. This review discusses the concept of a bidirectional lung-brain axis, illustrating that systemic responses to air pollutants like ozone may reflect and contribute to neurodegenerative processes in the CNS. By delineating these mechanisms, we emphasize the critical need for integrating environmental health management into strategies for the prevention and treatment of dementia.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities-specifically whether they originate in the inner or outer retina-remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease.

Background: Traumatic brain injury (TBI) increases the risk of developing Alzheimer's disease (AD), and a growing number of studies support a potential link between the two disorders. Therefore, the objective of this study is to systematically map the knowledge structure surrounding this topic over the past and to summarize the current state of research and hot frontiers in the field.

Methods: Data were retrieved from the Web of Science Core Collection (WOSCC) starting from the beginning until December 31, 2023, focusing on articles and reviews in English. Bibliometric tools including Bibliometrix R, VOSviewer, and Microsoft Excel were utilized for data analysis. The analysis included citations, authors, institutions, countries, journals, author keywords, and references.

Results: A total of 1,515 publications were identified, comprising 872 articles (57.56%) and 643 reviews (42.44%). The annual number of publications increased steadily, especially after 2013, with an R² value of 0.978 indicating a strong upward trend. The USA was the leading country in terms of publications (734 articles), followed by China (162 articles) and the United Kingdom (77 articles). Meanwhile Boston University was the most productive institution. Collaborative networks show strong collaborative author links between the USA and the United Kingdom, as well as China. The analysis also showed that the Journal of Alzheimer's Disease was the most productive journal, while the article authored by McKee achieved the highest local citations value. The top three author keywords, in terms of occurrences, were "Alzheimer's disease," "traumatic brain injury," and "neurodegeneration." Thematic mapping showed a consolidation of research themes over time, decreasing from 11 main themes to 8. Emerging themes such as "obesity" and "diffusion tensor imaging" indicate new directions in the field.

Conclusion: The research on AD after TBI has attracted a great deal of interest from scientists. Notably, the USA is at the forefront of research in this field. There is a need for further collaborative research between countries. Overall, this study provides a comprehensive overview of developments in TBI and AD research, highlighting key contributors, emerging topics, and potential areas for future investigation.

Background: Previous studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson's disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients.

Methods: This crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients.

Results: Forty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p < 0.001, GRF corrected). The ALFF value in the right superior parietal lobule during real taVNS was negatively correlated with the Unified Parkinson's Disease Rating Scale Part III (r = -0.417, p = 0.004, Bonferroni corrected).

Conclusion: TaVNS could immediately modulate the functional activity of brain regions involved in superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus. These findings offer preliminary insights into the mechanism of taVNS in treating PD and bolster confidence in its long-term therapeutic potential. TaVNS appears to reduce ALFF values in specific brain regions, suggesting a potential modulation mechanism for treating PD.

Introduction: Brain age is a machine learning-derived estimate that captures lower brain volume. Previous studies have found that brain age is significantly higher in mild cognitive impairment and Alzheimer's disease (AD) compared to healthy controls. Few studies have investigated changes in brain age longitudinally in MCI and AD. We hypothesized that individuals with MCI and AD would show heightened brain age over time and across the lifespan. We also hypothesized that both MCI and AD would show faster rates of brain aging (higher slopes) over time compared to healthy controls.

Methods: We utilized data from an archival dataset, mainly Alzheimer's disease Neuroimaging Initiative (ADNI) 1 with 3Tesla (3 T) data which totaled 677 scans from 183 participants. This constitutes a secondary data analysis on existing data. We included control participants (healthy controls or HC), individuals with MCI, and individuals with AD. We predicted brain age using a pre-trained model and tested for accuracy. We investigated cross-sectional differences in brain age by group [healthy controls or HC, mild cognitive impairment (MCI), and AD]. We conducted longitudinal modeling of age and brain age by group using time from baseline in one model and chronological age in another model.

Results: We predicted brain age with a mean absolute error (MAE) < 5 years. Brain age was associated with age across the study and individuals with MCI and AD had greater brain age on average. We found that the MCI group had significantly higher rates of change in brain age over time compared to the HC group regardless of individual chronologic age, while the AD group did not differ in rate of brain age change.

Discussion: We replicated past studies that showed that MCI and AD had greater brain age than HC. We additionally found that this was true over time, both groups showed higher brain age longitudinally. Contrary to our hypothesis, we found that the MCI, but not the AD group, showed faster rates of brain aging. We essentially found that while the MCI group was actively experiencing faster rates of brain aging, the AD group may have already experienced this acceleration (as they show higher brain age). Individuals with MCI may experience higher rates of brain aging than AD and controls. AD may represent a homeostatic endpoint after significant neurodegeneration. Future work may focus on individuals with MCI as one potential therapeutic option is to alter rates of brain aging, which ultimately may slow cognitive decline in the long-term.

Objective: This study aimed to analyse the relevant factors that may affect post-stroke fatigue (PSF) in patients with stroke and further explore the correlation between family functioning and PSF.

Methods: Patients who had experienced a first episode of stroke and were admitted to the Department of Neurology of the First Affiliated Hospital of Wenzhou Medical University were rigorously screened. The general data and family functioning of the patients on admission were collected, and their family adaptation, partnership, growth, affection and resolve scores and their PSF on the 5th day of admission were collected using the fatigue severity scale (FSS). Multiple linear regression analysis was then utilized to explore the factors affecting PSF in patients with stroke.

Results: A total of 220 questionnaires were distributed, and 220 were returned, with 212 valid questionnaires and a valid return rate of 96.4%. These 212 patients had a family functioning score of 6.58 ± 2.00 and an FSS score of 36.62 ± 10.96. Spearman's correlation analysis showed negative correlations between the FSS scores and the adaptation, partnership, growth, affection, resolve and family functioning scores (r = -0.380, -0.505, -0.470, -0.303, -0.281 and -0.712, respectively; p < 0.001). Furthermore, multiple linear regression analysis showed that family functioning (β' = -0.516), marital status (β' = -0.244), household income (β' = -0.185), literacy (β' = -0.181) and activities of daily living (β' = -0.084) were influential factors for PSF in patients with stroke (p < 0.05).

Conclusion: There is a significant negative correlation between family functioning and PSF, suggesting that better family functioning may help mitigate the severity of post-stroke fatigue. Healthcare providers should identify interventions to help patients and families address fatigue, boost disease recovery, promote patients' physical and mental health and improve their quality of life.

Alzheimer's disease, the most common form of dementia among older adults, slowly destroys memory and thinking skills. In recent years, scientists have made tremendous progress in understanding Alzheimer's disease, still, they do not yet fully understand what causes the disease. This article proposes a novel etiology for Alzheimer's disease. Our hypothesis developed from a review of nuclear medicine scans, in which the authors observed a significant increase in nasal turbinate vasodilation and blood pooling in patients with hypertension, sleep apnea, diabetes and/or obesity, all risk factors for Alzheimer's disease. The authors propose that nasal turbinate vasodilation and resultant blood pooling lead to the obstruction of normal nasal lymphatic clearance of cerebrospinal fluid and its waste products from the brain. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs alongside the well-established increased sympathetic activity of the cardiovascular system as seen in patients with hypertension. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of highly processed food associated with dysregulation of the glucose regulatory system. The authors' hypothesis offers a novel mechanism and a new paradigm for the etiology of Alzheimer's disease and helps explain the rapid worldwide rise in the disease and other dementias which are expected to double in the next 20 years. This new paradigm provides compelling evidence for the modulation of the parasympathetic nervous system as a novel treatment strategy for Alzheimer's disease and other degenerative brain diseases, specifically targeting nasal turbinate lymphatic flow.