Frontiers in Aging Neuroscience最新文献

Background and purpose: Accurately defining cognitive function trajectories in elderly ischemic stroke patients is crucial for identifying high-risk groups for cognitive decline, enabling timely personalized interventions to improve long-term outcomes and reduce familial and societal burdens. However, research on the heterogeneity of cognitive trajectories and their underlying causes in elderly Chinese patients with ischemic stroke remains limited. This prospective longitudinal study aimed to detect unique trends in cognitive trajectories among these patients and assess the contributing factors.

Methods: Validated assessment tools were utilized to systematically evaluate cognitive function at various specified intervals. Latent variable growth models were employed to delineate distinct subgroups of cognitive trajectories and to assess the predictive relevance of baseline pathophysiological markers and influencing factors in distinguishing these trajectories.

Results: Cognitive trajectories were categorized into three latent groups: the High Cognitive Function-Slow Decline Group (51%), the Low Cognitive Function-Intermediate Decline Group (34%), and the Low Cognitive Function-Rapid Decline Group (15%). Logistic regression analysis revealed that age, temporal lobe infarction, serum homocysteine levels, National Institutes of Health Stroke Scale score, and Multidimensional Perceived Social Support Scale score, were significant predictors of cognitive function (p < 0.05).

Conclusion: Geriatric patients with ischemic stroke have a gradual decline in cognitive function over time. Cognitive change trajectories can be categorized into three latent groups: High Cognitive Function-Slow Decline Group, Low Cognitive Function-Intermediate Decline Group, and Low Cognitive Function-Rapid Decline Group. Healthcare practitioners can develop tailored intervention strategies based on individual patients' cognitive trajectories and influencing factors to reduce cognitive decline and improve quality of life.

Introduction: Amnestic mild cognitive impairment (aMCI), serving as a clinical precursor to Alzheimer's Disease (AD), assumes a pivotal role in the early stages of AD prevention. The longitudinal collection of data in aMCI is imperative for monitoring disease progression and guiding clinical interventions.

Methods: Utilizing a prospective cohort design, we recruited aMCI individuals and conducted a one-year follow-up study. During this period, electroencephalogram (EEG) signals were systematically collected at regular intervals, resulting in four time points for each participant. Based on the follow-up outcomes, participants were stratified into progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) groups. We extracted spectral, nonlinear, and functional connectivity features from the EEG data at three cross-sectional time points in the initial nine months and constructed longitudinal features between these cross-sectional assessments. The longitudinal features were fed into machine learning classifiers to predict one-year follow-up outcomes.

Results: The dynamic trends of EEG features in SMCI and PMCI patients exhibited inconsistency. Utilizing the selected longitudinal features, the support vector machine (SVM) demonstrated the best prediction performance, achieving an accuracy of 94.92%, an area under the curve of 93.25%, a sensitivity of 90.20%, a specificity of 98.80%, a positive predictive value of 98.70%, and an F1-score of 93.65%.

Discussion: By capturing trend information associated with disease progression, longitudinal EEG features contributed to enhancing prediction performance in machine learning models.

Alzheimer's disease is widely viewed as a disorder of disturbed amyloid-β (Aβ) homeostasis, yet it remains unclear why Aβ shifts from routine turnover to progressive retention and plaque growth in mid-life. This article advances a mechanochemical hypothesis: that age-related reductions in low-intensity mechanical vibrations in the head and neck-arising from everyday self-vocalization (speech, singing, humming) and physiological, non-hypoxic upper-airway motion during stable sleep-contribute to a gradual narrowing of the Aβ clearance bottleneck. Gentle vibrations transmitted through bone and soft tissue could, in principle, enhance interstitial mixing, reduce local supersaturation and nucleation, increase encounter rates at blood-brain barrier and meningeal-lymphatic interfaces, and augment perivascular and glymphatic transport. A sustained decline in this "intrinsic mechanical vibration" (IMV) dose in mid-life might therefore favor Aβ retention without any change in production. We bring together indirect lines of evidence that are compatible with this view, including sleep and glymphatic studies, neuromodulatory stimulation paradigms, music and singing interventions, and hearing-loss epidemiology, and we discuss domains that at first appear inconsistent, such as voice-heavy occupations and obstructive sleep apnea. We then outline a testable cascade that links behavioral and sleep changes in mid-life to reduced mechanical drive and impaired clearance, and we propose concrete experiments spanning human laboratory studies, clinical trials, animal models, and prospective cohorts. Whether ultimately supported or refuted, this IMV-clearance framework highlights mechanical forces as a potentially modifiable dimension of Alzheimer's disease risk and treatment response, alongside sleep, vascular health, and cognitive engagement.

Alzheimer's disease (AD) represents a continuously advancing neurodegenerative condition distinguished by the unremitting deterioration of cognitive abilities and memory impairment, which significantly hampers daily functioning of life. In the absence of disease modifying treatments, it continues to pose a significant global challenge. Though symptomatic treatment exists, the inherent complexity involved with AD pathogenesis related to Aβ plaques, neurofibrillary tangles, neuroinflammation, oxidative stress, etc. poses a tremendous challenge to developing drugs. With the incidence of AD increasing yearly globally, research into already existing pharmacological agents has the potential to uncover a brighter future for breakthroughs in treatment strategy. A primary strategy to accelerate the development of AD therapies is drug repurposing: determining a new use for an existing known medication. Following innovative approaches like high-throughput screening, AI-based techniques, a number of classes of drugs originally designed for other diseases are now being tested to modulate the complex pathology mechanisms in AD. This review focuses on the therapeutic promise of drug repurposing as adjunctive to the much-needed renaissance in AD therapies. The review continues to focus on some promising repurposed drug candidates, methodologies applied, and the evaluation of the present status of drugs in the clinic. Apart from the information regarding mechanisms involved in AD, this review also complements case studies, challenges, and limitations along with the various drug repurposing strategies for AD. By understanding and harnessing the potential of existing pharmacological agents, we can expand therapeutic options and improve patient outcomes.

Long COVID (LC) is a multisystem, post-infectious conditions diagnosed ≥3 months after acute SARS-CoV-2 infection and marked by relapsing, persistent, or progressive symptoms, especially fatigue, post-exertional symptom exacerbation and neuropsychiatric syndromes. We synthesized evidence suggesting that LC arises from intersecting pathways including viral persistence, intestinal dysbiosis and barrier compromise with microbial translocation, innate immune activation with neutrophil extracellular traps (NET) and thromboinflammation, and immune dysregulation with features of exhaustion and autoimmunity. These processes adversely impact blood-brain barrier (BBB) function and lead to neuroinflammation. We propose a mechanistic model in which viral antigens and translocated microbial products amplify pro-inflammatory networks promoting immunothrombosis and tissue hypoperfusion. Hematogenous and gut-brain pathways may then deliver inflammatory mediators to the central nervous system (CNS), resulting in BBB disruption and glial activation that underpin nervous system disorders in LC. Treatment regimens aimed at lowering antigen load, restoring mucosal barrier integrity and modulating myeloid/coagulation pathways may warrant investigation as novel therapeutic strategies to treat LC.

Human cytomegalovirus (HCMV), a ubiquitous DNA betaherpesvirus, is capable of persistent infection and immunomodulation, particularly in immunocompromised and elderly hosts. Emerging evidence links HCMV to neurodegenerative diseases through its multifaceted immunomodulatory effects. This review summarizes key viral architectures and mechanisms, epidemiological trends, and experimental data supporting HCMV's role in cognitive decline. We advocate for targeted antiviral strategies and vaccine development to clarify its contribution to neurodegeneration.

Alzheimer's disease (AD), the most common form of dementia, is characterized by two hallmark pathologies, amyloid plaques (APs) and neurofibrillary tangles (NFTs). Amyloid-β and tau, key components of APs and NFTs, respectively, are widely considered primary drivers of neurodegeneration in AD. In contrast, an alternative view proposes that network failure, arising from amyloid-β precursor protein-driven excessive/aberrant and maladaptive synaptic plasticity, underlies AD pathophysiology. Synaptic plasticity is indispensable for cognitive functions such as learning and memory; however, when dysregulated, it may lead to cognitive decline and accelerate the trajectory toward AD. This paper, based on this hypothesis, examines strategies to mitigate maladaptive plasticity while preserving adaptive plasticity, and proposes the potential of novel approaches for the prevention and treatment of mild cognitive impairment and AD, encompassing both activity-based interventions and pharmacological treatments. This hypothesis-driven framework offers a coherent perspective linking molecular, circuit, and cognitive levels of dysfunction in AD, and may guide more integrative, multi-level approaches to future preventive and therapeutic strategies, a direction increasingly emphasized in current experimental and clinical AD research.

Background: Mild behavioral impairment (MBI) is recognized as a potential early marker for dementia and may be indicative of the increased risk in the predementia stage. This study investigated whether MBI could moderate the impact of white matter hyperintensities (WMHs) on late-life cognitive function in patients with arteriosclerotic cerebral small vessel disease (aCSVD).

Methods: Patients were categorized into two groups based on Fazekas scores: low WMH burden (LWMH, scores 1-2; n = 119) and high WMH burden (HWMH, scores 3-6; n = 110). Logistic regression analysis was used to assess the associations among WMH, MBI, and screen-positive cognitive impairment. Moderation analysis was conducted to evaluate whether the presence of MBI could influence the relationship between WMH and cognitive outcomes.

Results: WMH was associated with MBI (p < 0.001) and screen-positive cognitive impairment (MoCA: p = 0.003; MMSE: p = 0.025), and MBI was correlated with screen-positive cognitive impairment (p = 0.010 and 0.007, respectively). HWMH was independently correlated with screen-positive cognitive impairment and MBI (p = 0.001; p < 0.001; p = 0.031). Compared with cases in the non-MBI group, those in the MBI group had more WMHs in the occipital lobes (p = 0.016) and subcortical structures (p = 0.042). Furthermore, MBI significantly moderated the association between WMH and screen-positive cognitive impairment (β = -0.10, p < 0.014; β = -0.06, p < 0.041).

Conclusion: The presence of MBI may exacerbate the cognitive decline associated with WMH in patients with aCSVD. These findings highlight the importance of early identification and monitoring of MBI in cases with WMH to better assess dementia risk and to develop interventional strategies.

Aim: Studies indicate that semantic fluency improved after cochlear implantation (CI) in older adults, but not in young and middle-aged adults. We were interested in identifying cognitive variables that are associated with this improvement. We tested whether improvements in cognition after cochlear implantation are associated with improvements in semantic fluency in older adults.

Methods: We used data from a multicenter cohort study. All dementia-free CI patients had symmetrical hearing loss that started in adulthood. The younger group (n = 20) was aged 25 and 59 years, and the older group (n = 21) was aged between 60 and 75 years. All participants underwent word fluency tests, as well as tests of working memory, cognitive flexibility, inhibition, and verbal episodic memory, immediately before and 12 months after the CI.

Results: Semantic fluency and working memory improved significantly in the older group. No significant improvement was found in the younger group. The improvement in semantic fluency in the older group correlated significantly with the improvement in working memory. Mediation analyses suggest a partial overlap between improvements in semantic fluency and working memory. The improvement in working memory accounted for 28% of the enhancement in semantic fluency.

Conclusion: In older adults with hearing loss, enhanced working memory after CI did not fully mediate the relationship between CI and semantic fluency. Additional variables that also improved after CI may influence semantic fluency.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, and synaptic dysfunction. In recent years, 40 Hz sensory stimulation-including visual, auditory, and multimodal modalities-has emerged as a novel, non-invasive intervention demonstrating potential efficacy in both animal models and preliminary clinical studies. Preclinical evidence indicates that such stimulation can markedly reduce cerebral Aβ burden (by approximately 37%-53%), inhibit tau protein phosphorylation, enhance neuronal network synchrony and synaptic plasticity, and improve learning and memory performance. Limited human trials suggest that 40 Hz sensory stimulation is safe and well tolerated in patients with mild cognitive impairment (MCI) and early-stage AD, with a slowing trend in cognitive scale score decline following intervention. This review summarizes the mechanisms of action, experimental evidence from animal models, and advances in clinical application of 40 Hz sensory stimulation in AD prevention and treatment. It further explores the potential for multimodal combination therapies integrating sensory stimulation with cognitive training, pharmacological interventions, and lifestyle modifications, and addresses challenges such as optimal timing of intervention and the influence of ambient electromagnetic fields in real-world settings. Current evidence supports 40 Hz sensory stimulation as a feasible, multi-target, and safe adjunctive intervention; however, its efficacy and applicability must be verified through multicenter, randomized controlled trials with long-term follow-up.