Frontiers in Aging Neuroscience最新文献

Objective: The number of people with dementia and cognitive impairment is rising every year as the older population grows. The higher prevalence and mortality rates of dementia and cognitive impairment place an enormous burden on healthcare and economic systems worldwide. Studies have shown that older adults with sensory impairments are at a higher risk of developing dementia and cognitive impairment than normal older adults. There is a lack of systematic reviews on the relationship between sensory impairment and dementia and cognitive impairment in older persons. This meta-analysis aimed to analyze the correlation of visual impairment, hearing impairment, and dual sensory impairment with dementia and cognitive impairment, and to provide guidance for reducing the incidence of dementia and cognitive impairment in older adults.

Methods: Computerized searches were conducted using the CNKI, Wanfang, Vip, Sinomed, PubMed, Web of Science, Cochrane Library, and Embase databases. Supplementary searches were performed on 2 clinical trial registries.

Results: Meta-analysis was performed by log-transforming the study-specific estimates. The heterogeneity of studies was characterized by Q-test and I ². The results of the studies indicated that dual sensory impairment was associated with dementia [OR 95% CI 1.66 (1.47, 1.86)], visual impairment was associated with dementia [OR 95% CI 1.60 (1.48, 1.74)], hearing impairment was associated with dementia [OR 95% CI 1.26 (1.22, 1.31)], dual sensory impairment was associated with cognitive impairment [OR 95% CI 2.08 (1.70, 2.54)], visual impairment was associated with cognitive impairment [OR 95% CI 1.84 (1.44, 2.36)], and hearing impairment was associated with cognitive impairment in old age [OR 95% CI 1.50 (1.36, 1.65)].

Conclusion: Sensory impairment is a predictor of dementia and cognitive impairment. Healthcare professionals should prioritize screening older adults with sensory impairments to reduce the incidence of dementia and cognitive impairment.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024606342.

Background: The early differential diagnosis of Parkinson's disease (PD) and atypical parkinsonian syndromes (APSs) poses challenges. The current methods, which rely on clinical assessments and single-modal biomarkers, lack sufficient sensitivity and specificity. This study aims to develop a multidimensional model integrating plasma biomarkers, clinical parameters, and neuroimaging radiomic features to improve the accuracy of differentiating PD from APS.

Methods: A total of 150 participants were enrolled in the study, including 56 healthy controls (HC), 54 patients with PD, and 40 patients with APSs. Plasma biomarkers (NFL, GFAP, α-syn, and tau), clinical indicators (e.g., disease duration and UPDRS-III scores), and radiomic features (1,316 IBSI-standardized features) from magnetic resonance imaging scans of the midbrain and pons were collected. Core variables were screened using LASSO regression and random forest algorithms, and a multivariate logistic regression model was constructed. The performance of the model was evaluated using receiver operating characteristic curves, calibration curves, and cross-validation.

Results: Plasma GFAP and NFL levels showed a significant gradient change: APS group (GFAP: 89.9 pg./mL; NFL: 77.3 pg./mL) > PD group (GFAP: 47.1 pg./mL; NFL: 50.0 pg./mL) > HC group (GFAP: 22.1 pg./mL; NFL: 37.5 pg./mL; p < 0.05). The levels of α-syn and tau in the PD and APS groups were significantly higher than those in the HC group (p < 0.001), but there was no difference between the two groups. Four core variables (NFL, GFAP, disease duration, and pontine voxel volume) were selected. The area under the curve (AUC) of the combined model for identifying PD and APS was 0.874 (95% confidence interval: 0.801-0.946), which was significantly higher than that of single variables (such as NFL alone AUC = 0.653). Cross-validation confirmed the stability of the model (AUC = 0.843).

Conclusion: This was the first study to integrate plasma NFL/GFAP, clinical disease duration, and pontine radiomic features to construct a high-precision PD-APS differential model (AUC > 0.87), addressing the limitations of traditional single-mode approaches. The gradient changes in GFAP and the APS-specificity of NFL serve as key biomarkers. Thus, this multidimensional framework provides a practical diagnostic tool for resource-limited scenarios.

Introduction: Oropharyngeal dysphagia (OD) is a common and significant complication of Parkinson's disease (PD), contributing to malnutrition, respiratory complications and impaired medication intake. The pathophysiology of OD in PD is heterogeneous, involving basal ganglia dysfunction with associated motor impairments in the oropharynx, cortical pathophysiology, and α-synuclein pathology in peripheral nerves. While deep brain stimulation (DBS) is an established intervention for motor symptom management in PD, its effects on swallowing function remain poorly understood and controversial. This narrative review aims to critically evaluate the current evidence on the effects of DBS on OD in PD and to outline potential future research directions, grounded in current understanding of OD pathophysiology and DBS mechanisms.

Methods: A narrative review of clinical studies examining the effects of DBS on swallowing function in people with PD was conducted. Studies were identified through database searching of MEDLINE, Embase and Cochrane Library, from inception of the databases until May 2025. Inclusion criteria encompassed clinical studies and case reports investigating DBS effects on swallowing outcomes in people with PD, with no language restrictions applied. Data regarding study design, DBS intervention and stimulation parameters, swallow-related outcomes and assessment methods were extracted and compiled systematically.

Results: A total of 24 clinical studies, including prospective and retrospective observational studies and case reports, were included in this review. Evidence regarding DBS effects remains inconsistent. Subthalamic DBS shows the greatest variability: some studies report improvements in aspiration frequency or pharyngeal timing, while others describe no change or even long-term deterioration in swallowing safety. Pallidal DBS appears to neither improve nor deteriorate swallowing function, however, evidence is limited to four mainly retrospective studies with small sample sizes. Evidence on combined or alternative targets remains sparse and heterogeneous. Patient-reported swallowing outcomes are often more favorable than instrumental measures.

Discussion: DBS may influence swallowing in PD, but outcomes likely depend on OD phenotypes, stimulation targets and parameters. Future research should recruit adequately powered cohorts, apply standardized instrumental assessments including detailed OD phenotyping, systematically explore stimulation parameters, distinguish short- from long-term effects, and integrate OD outcomes into DBS programming.

Background: During non-rapid eye movement (NREM) sleep, cortical slow oscillation (SO; <1 Hz) and thalamic sleep spindle activity (12-15 Hz) interact through precise phase coupling to support memory consolidation. Slow oscillatory transcranial direct current stimulation (so-tDCS) can modulate these oscillations. Traditionally, anodal so-tDCS is used to depolarize the cortex during SO up-states, thereby promoting SO activity and SO-spindle coupling. However, intracranial findings suggest that SO down-states, characterized by cortical hyperpolarization, can trigger thalamic spindle bursts. This raises the hypothesis that cathodal so-tDCS, by promoting hyperpolarization, could selectively enhance down-states and more effectively improve SO-spindle coupling.

Methods: We tested this hypothesis in 22 healthy older adults, a population known to exhibit diminished NREM oscillatory activity. Each participant received cathodal, anodal, and sham so-tDCS in separate nap sleep sessions. We quantified SO and spindle characteristics, their temporal coupling, and cortical excitation/inhibition (E/I) balance using EEG spectral slope. We also assessed individual circadian preference (chronotype) as a potential moderator.

Results: We found that anodal so-tDCS improved SO-spindle synchrony and increased spindle power over sham in participants with intermediate or evening chronotypes, while cathodal so-tDCS did not enhance these oscillatory measures compared to sham, despite prolonging SO down-states. Anodal so-tDCS also shifted E/I balance toward increased excitability, indicating increased cortical excitability, whereas cathodal so-tDCS did not produce the anticipated opposite shift.

Conclusion: In summary, anodal, but not cathodal, so-tDCS effectively enhanced thalamocortical interactions underlying memory consolidation. Furthermore, these findings highlight the importance of individual factors such as chronotype in brain stimulation responsiveness.

Background: Rapid eye movement sleep behavior disorder (RBD) is increasingly recognized as both a prodromal marker and a significant predictor of Parkinson's disease (PD) progression. Despite a surge in related research, a comprehensive bibliometric evaluation summarizing the field's development, key contributors, and thematic evolution remains lacking. This study aimed to uncover the knowledge structure and emerging frontiers in RBD-related PD research through bibliometric analysis.

Methods: On September 1, 2,025, an extensive literature search was conducted in the Web of Science Core Collection and Scopus databases using standardized RBD-related PD keywords. Bibliometric analysis and knowledge mapping were performed with CiteSpace, VOSviewer, and R software.

Results: A total of 2,887 publications were identified, research output has increased steadily since 2013. Keyword co-occurrence and clustering analyses revealed three primary research directions: (1) longitudinal studies of RBD as a prodromal manifestation of synucleinopathies, (2) biomarker discovery for early diagnosis and disease monitoring, and (3) clinical interventions targeting sleep disturbances and neuroprotection. Notably, recent research trends emphasize non-motor symptoms of PD, overlapping mechanisms with Lewy body disease, and the application of advanced neuroimaging and digital sleep-monitoring technologies. Additionally, emerging keywords highlight biomarkers, gender differences, melatonin as focal points.

Conclusion: This bibliometric analysis provides a systematic overview of the RBD-related PD research landscape. It underscores the field's shift from clinical observation to mechanistic exploration and translational application. These findings may guide future studies aimed at improving early detection and developing individualized therapeutic strategies for patients with RBD and PD.

Alzheimer's disease (AD) is characterized by the accumulation of misfolded proteins that trigger neuroinflammation and neuronal loss. The retina, as an extension of the central nervous system, mirrors these pathological processes and represents a potential biomarker. Microglial activation, a key component of neuroinflammation, can be morphologically assessed through automated image analysis. This study performed a quantitative and morphological analysis of retinal microglia in the APP^NL-F/NL-F mouse model of AD across aging (6-20 months) and comparing them with age-matched C57BL/6 J controls using an automated image analysis software. A cross-sectional design was applied to 72 mice (36 APP^NL-F/NL-F and 36 WT). Retinas samples were processed by Iba-1 immunohistochemistry. Quantified parameters included cell number, soma size, arborization area, skeletonization, fluorescence intensity, and Feret's Diameter Ratio across OS, OPL, IPL, and NFL/GCL layers. Image analysis was performed using a custom automated system, called MorphoSomas, specifically developed for the comprehensive morphological assessment of microglia. Age-dependent changes were observed in both groups. WT mice showed a later and more gradual activation pattern, whereas APP^NL-F/NL-F mice exhibited early activation from 6 months, characterized by increased cell number and soma size, followed by reductions in arborization and skeletonization, indicating progressive activation. The automated system allowed precise and reproducible assessment, highlighting significant differences between groups and retinal layers. In conclusion, retinal microglia in APP^NL-F/NL-F mice exhibit early and biphasic activation followed by signs of dysfunction, reflecting AD neuropathology. Automated analysis enhances objectivity and efficiency in morphological studies. These findings support the retina as a promising, non-invasive biomarker for early AD detection.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of pathological α-synuclein. Although current treatments can alleviate symptoms, they do not modify disease progression. Growing evidence implicates gut microbiota dysbiosis and aberrant protein acetylation in PD pathogenesis. Electroacupuncture (EA) has shown therapeutic potential in PD; however, its effects on protein acetylation remain unclear.

Methods: A PD mouse model was established through MPTP induction and fecal microbiota transplantation (FMT) from PD patients. Mice received EA stimulation at Baihui (GV20) and Yanglingquan (GB34) acupoints for 14 days. Behavioral tests, immunohistochemistry, Western blot, qPCR, and 4D label-free acetyl proteomics were employed to assess motor function, neuronal integrity, protein expression, and acetylation profiles.

Results: EA significantly improved motor coordination, enhanced sensorimotor function in the adhesive removal test, and increased open-field activity in PD mice. It attenuated the loss of tyrosine hydroxylase-positive neurons and decreased α-synuclein accumulation in the substantia nigra. Proteomic analysis revealed hyperacetylation of Ywhaq (14-3-3) in PD mice, which was reversed by EA. Mechanistically, EA upregulated the expression of deacetylases HDAC1/2/3 and SIRT1/2 at both protein and mRNA levels, restoring acetylation homeostasis.

Conclusion: Electroacupuncture ameliorates behavioral and neuropathological phenotypes in a PD mouse model by restoring deacetylase expression and normalizing protein acetylation, particularly of 14-3-3. Our results underscore the therapeutic potential of EA and highlight acetylation modulation as a promising strategy for PD treatment.

Introduction: Neurodegeneration in multiple sclerosis leads to progressive cognitive and motor impairments. Cardiorespiratory fitness (CRF) is thought to protect against such decline, but its longitudinal effects remain unclear. This study examined whether CRF predicts changes in behavioral (i.e., hand dexterity and cognition) and neurophysiological (i.e., corticospinal excitability, an indicator of corticospinal tract function) outcomes in multiple sclerosis over 2 years, with a focus on participants who experienced no relapses between visits and were, therefore, classified as progression independent of relapse activity (PIRA). We hypothesized that higher baseline CRF would be associated with better follow-up outcomes.

Methods: Participants underwent assessments at two time points (∼2 years apart). CRF was measured using a graded maximal exercise test ( $\stackrel{.}{V}$ O₂max). Behavioral outcomes included the Nine-Hole Peg Test and Montreal Cognitive Assessment. Corticospinal excitability was assessed via transcranial magnetic stimulation of the first dorsal interosseous muscle. Hierarchical regression analyses examined whether baseline CRF predicted change in follow-up scores, controlling for age, sex, and baseline performance.

Results: Among 38 participants (71% female), CRF at baseline did not significantly predict changes in behavioral or physiological outcomes (p = 0.178-0.655). Instead, baseline performance was the strongest predictor of follow-up scores. Exploratory analyses revealed inter-individual variability, with some participants improving, declining, or remaining stable over the 2 years. Significant improvements were observed in the Montreal Cognitive Assessment (p = 0.002) and non-dominant hand Nine-Hole Peg Test (p = 0.036).

Discussion: CRF did not predict longitudinal changes in manual dexterity, cognition or corticospinal excitability in individuals living with multiple sclerosis. Instead, initial performance was the primary determinant of follow-up outcomes, suggesting that achieving better function at baseline (earlier in the disease) is an important rehabilitation target. Variability in longitudinal change underscores the heterogeneous nature of disease progression/improvement and the need for specific, targeted interventions and personalized strategies to disease management.

Objectives: This study aimed to characterize serum exosomal miRNA profiles from patients with age-related hearing loss (ARHL) to identify key pathogenesis-related miRNAs for ARHL.

Methods: Peripheral venous blood samples were collected from patients with ARHL and elderly controls, and exosomes were isolated from serum of each subject. Then, the isolated exosomes were systematically identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot. Subsequently, the isolated exosomes were submitted for miRNA sequencing and a series of bioinformatics analysis. Ultimately, four key DE-miRNAs, namely hsa-miR-100-5p, hsa-miR-23b-3p, hsa-miR-373-3p, and hsa-miR-27b-3p, were verified using quantitative real-time polymerase chain reaction (RT-qPCR).

Results: NTA, TEM and western blot confirmed exosomes were successfully isolated. After sequencing, 22 differential expressed miRNAs (6 up-regulation and 16 down-regulation) were identified between the exosomes from ARHL and controls, and then collectively identified 17,451 predicted target genes and 15,863 experimentally validated target genes. Gene Ontology enrichment analysis revealed that the target genes were significantly associated with "regulation of neuron projection development," "sensory system development," "proteasome-mediated ubiquitin-dependent protein catabolism," and "ubiquitin-like protein ligase binding." Kyoto Encyclopedia of Genes and Genomes (KEGG) showed the target genes were significantly enriched in "PI3K-Akt signaling pathway," "MAPK signaling pathway," "cellular senescence," "autophagy," "mTOR signaling pathway," "ubiquitin-mediated proteolysis," and "signaling pathways regulating stem cell pluripotency." Additionally, the Reactome analysis highlighted the involvement of "MAPK family signaling cascades," "negative regulation of the PI3K/AKT network," and "antigen processing: ubiquitination and proteasome degradation." Disease Ontology further demonstrated significant enrichment of target genes in neurological disorders. RT-qPCR showed hsa-miR-100-5p and hsa-miR-23b-3p exhibited markedly decreased levels, while hsa-miR-373-3p and hsa-miR-27b-3p were significantly up-regulated in ARHL, which were consistent with sequencing results, confirming a high relatively reliability of the sequencing results.

Conclusion: Ubiquitination modification, autophagy process, cellular senescence and nervous system regulation may jointly contribute to the core molecular mechanism of ARHL. The hsa-miR-100-5p, hsa-miR-23b-3p, hsa-miR-373-3p, and hsa-miR-27b-3p may preliminarily act as key regulatory factors to participate in the pathophysiological process of ARHL, providing exploratory evidence for their potential application value as molecular markers.

Background: Guidelines currently suggest considering EEG guidance during general anesthesia in elderly patients to avoid prolonged burst suppression (BS), with the aim of mitigating postoperative delirium (POD). Our study aimed to investigate the association between POD and intraoperative BS duration dependent on the general anesthetic agent used (propofol vs. sevoflurane).

Methods: In this prospective study (2019-2022), EEGs from 265 patients over 70 years undergoing general anesthesia were analyzed for intraoperative BS duration both visually and using one new automated algorithm to evaluate its accuracy. Associations between BS duration, anesthetic agent, and postoperative delirium (POD) were evaluated using multivariable logistic regression, adjusting for confounders.

Results: BS duration was markedly shorter than in prior cohorts but did not reduce overall postoperative delirium (POD) incidence. POD occurred more frequently with sevoflurane than propofol (44% vs. 30%, p = 0.017), despite shorter median BS [0 s (IQR 0-4.9) vs. 20.6 s (IQR 0-151.7); p = 0.012]. A significant interaction between anesthetic agent and BS (p = 0.033) showed that BS under sevoflurane conferred 3.8-fold greater POD risk than under propofol. Sevoflurane plus BS increased POD odds 9.3-fold compared to propofol without BS. Our new automated BS detection algorithm demonstrated high precision (median error <2.17 s).

Conclusion: Sevoflurane markedly increased POD risk versus propofol, independent of BS duration. Sevoflurane and BS interaction amplified delirium odds. BS appears a vulnerability marker rather than a causal factor. The validated machine-learning BS detector offers a reliable tool for future EEG-based delirium risk research.