Frontiers in Aging Neuroscience最新文献

Parkinson's disease (PD) is the selective demise of dopaminergic neurons in the substantia nigra. Conventional neuroprotective strategies based on exogenous antioxidants have shown minimal clinical efficacy. Emerging evidence suggests that neuronal loss in PD may stem not only from direct mitochondrial damage but, more critically, from the failure of an intrinsic "early-warning system"-the mitochondrial retrograde signaling (MRS) pathway-impairing the nucleus's ability to launch timely protective responses. This review repositions pterostilbene, a bioavailable dietary polyphenol, from a simple antioxidant to a "signal fidelity enhancer" that supports mitochondria-to-nucleus communication. By stabilizing mitochondrial function and modulating stress-sensing pathways, pterostilbene may restore MRS integrity and promote activation of endogenous defense mechanisms such as the mitochondrial unfolded protein response (UPRmt). The article advocates a paradigm shift in nutritional neuroprotection: from passive supplementation toward reinforcing the neuron's intrinsic capacity for self-maintenance and resilience.

Background: Parkinson's disease (PD) is traditionally defined by dopaminergic degeneration and α-synuclein aggregation. However, mounting evidence supports a multifactorial and systemic pathophysiology that extends beyond the central nervous system. This narrative review explores the interconnected mechanisms underlying sporadic PD, including environmental exposures, gut dysbiosis, α-synuclein pathology and propagation, systemic and neuroinflammation, metabolic dysfunctions (notably insulin and lipid metabolism), sleep disturbances, glymphatic impairment, and proteostatic failure.

Results: The review highlights how α-synuclein pathology can originate peripherally, particularly in the enteric nervous system, and propagate to the brain via neuronal or hematogenous routes. It also examines the synergistic roles of systemic inflammation, immune dysregulation, mitochondrial dysfunction, and impaired protein clearance in promoting neurodegeneration.

Conclusion: Collectively, these findings support a reconceptualization of PD as a systemic neurodegenerative disorder involving complex crosstalk between peripheral and central pathways. Understanding these multifaceted interactions opens new avenues for early diagnosis, biomarker discovery, and disease-modifying therapeutic strategies targeting the gut-brain axis, metabolic homeostasis, and proteostasis.

Introduction: Urinary dysfunction is a common non-motor symptom in patients with Parkinson's disease (PD) and is often associated with greater motor disability and reduced quality of life. Despite its clinical relevance, the association between motor symptom severity and urinary dysfunction remains poorly understood. This study aimed to elucidate this relationship using validated clinical questionnaires to assess urinary symptoms.

Methods: We conducted a single-center, retrospective cross-sectional study including 223 patients with PD who visited a university hospital between September 2023 and February 2024. Urinary dysfunction was evaluated using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), comprising the symptom (IPSS-symptom score; Q1-7) and satisfaction (IPSS-satisfaction score; Q8) scores. We analyzed the changes in urinary symptoms, overall satisfaction, and prodromal symptoms across the Hoehn and Yahr (HY) stages. Patients were divided into early (HY ≤ 2) and late (HY > 2) groups to assess early urinary symptom changes.

Results: The OABSS, IPSS-symptom score, and IPSS-satisfaction score significantly increased with advancing HY stage. Compared to the early group, the late group exhibited significantly higher OABSS (p = 0.015), IPSS-symptom scores (p = 0.002), and IPSS-satisfaction scores (p < 0.001). Subgroup analysis of the IPSS revealed that storage symptoms compared with voiding symptoms correlated more strongly with motor severity.

Conclusion: Our study provides evidence that urinary dysfunction intensifies with motor symptom progression in PD. These findings highlight the importance of early detection and proactive management of urinary symptoms in patients with PD to enhance their overall quality of life.

Background: Red blood cell distribution width (RDW) is associated with increased mortality risk in critically ill patients. However, limited data are available on critically ill patients with delirium.

Methods: Data from the Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 3.1 database were analyzed in this retrospective cohort research. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) criteria were used to identify critically ill patients with delirium. The first RDW value was extracted within the first 24 h after intensive care unit admission. The endpoint was 30-day all-cause mortality. Multivariable Cox regression analysis was performed to examine the relationship between RDW and 30-day mortality. Age, sex, myocardial infarction, congestive heart failure, peripheral vascular disease, dementia, cerebrovascular disease, chronic pulmonary disease, diabetes, sepsis, and hemoglobin were considered for subgroup analysis.

Results: A total of 10,600 patients were included, with a mean (standard deviation) age of 67.0 (16.7) years, of whom 6,007 (56.7%) were male patients. The increase in RDW was correlated with an increased risk of 30-day mortality in the Cox proportional regression analysis model (Hazard Ratio [HR] 1.04; 95% confidence interval [CI] 1.03-1.04). In comparison with the low-RDW group, the middle and high-RDW groups tended to have higher risks of 30-day all-cause mortality (HR, 1.54; [95% CI] [1.34-1.77]; HR 2.25 [95% CI] [1.96-2.58]; P trend < 0.0001). Restricted cubic spline (RCS) analysis demonstrated linear relationships between RDW and 30-day mortality. Subgroup analyses using the entire cohort also demonstrated higher 30-day all-cause mortality. Subgroup analyses across the entire cohort confirmed elevated 30-day all-cause mortality associated with higher red cell distribution width (RDW), with results aligning closely with the Cox proportional regression findings.

Conclusion: An increase in RDW was associated with an increased risk of 30-day all-cause mortality in critically ill patients with delirium. RDW may serve as a valid indicator for assessing the severity and guiding the treatment of delirium patients in the ICU.

Background: Cognitive impairment in Parkinson's disease (PD-CI) is a prevalent non-motor symptom, significantly diminishing quality of life and imposing a substantial family burden. Effective predictive tools are currently scarce, and the diagnostic pathway is intricate. With the growing use of artificial intelligence in healthcare, machine learning (ML) methodologies have been explored for the diagnosis and early risk prediction of PD-CI; however, their efficacy and accuracy necessitate systematic evaluation. Consequently, this investigation undertook a systematic review and meta-analysis.

Method: A comprehensive literature retrieval was conducted across Web of Science, PubMed, Embase, and Cochrane Library, encompassing studies published from database inception to August 10, 2025. The PROBAST tool facilitated quality appraisal, ultimately incorporating 52 publications, of which 25 addressed diagnosis and 27 focused on risk prediction.

Results: Findings indicated that within the validation cohorts, ML models for PD-CI diagnosis achieved a c-index of 0.82, with a sensitivity of 0.57 and specificity of 0.77. For PD-CI risk prediction, the c-index reached 0.83, accompanied by a sensitivity of 0.77 and specificity of 0.76. These results suggest that ML exhibits considerable accuracy in both the diagnosis and risk prediction of PD-CI. The models primarily incorporated variables such as clinical data, genetic characteristics, biomarkers, neuroimaging, and radiomics, and no overt signs of overfitting were detected.

Conclusion: This research provides an evidence-based foundation for the future development of PD-CI risk prediction and intelligent diagnostic tools, thereby promoting the advancement and application of ML within Parkinson's disease and related domains.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, ID: CRD42023453586.

Objective: Subsyndromal symptomatic depression (SSD) has been increasingly implicated in the pathophysiological processes of Alzheimer's disease (AD). However, it remains unclear whether SSD and amyloid-β (Aβ) pathology jointly contribute to tau deposition. This study aimed to investigate the interaction between SSD and Aβ status on regional tau accumulation in non-demented older adults.

Materials and methods: We analyzed data from 391 non-demented older adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent Aβ and tau positron emission tomography (PET) scans, as well as Geriatric Depression Scale (GDS-15) assessments. Aβ positivity (Aβ+) was defined by established tracer-specific standardized uptake value ratio (SUVR) thresholds (≥1.11 for ¹⁸F-florbetapir or ≥1.08 for ¹⁸F-florbetaben). SSD was defined as a GDS-15 score of 1-5. Linear mixed-effects models were applied to assess the longitudinal effects of SSD and Aβ status on regional tau accumulation over 2 years.

Results: At baseline, significant interactions between SSD and Aβ status were observed for regional tau SUVRs, with the Aβ+/SSD+ group exhibiting significantly higher tau levels across all Braak stages compared with the other groups. Longitudinal analyses identified a significant three-way interaction among SSD, Aβ status, and time in the Braak III/IV and Braak V/VI regions. Moreover, the Aβ+/SSD+ group demonstrated significantly faster tau accumulation compared to all other groups. The Aβ+/SSD- group also exhibited greater tau accumulation than the Aβ-/SSD- group, whereas no significant differences were observed between the Aβ- groups.

Conclusion: These findings suggest that SSD is associated with greater early tau accumulation in individuals with Aβ pathology.

Objectives: Symptomatic stenosis of the extracranial vertebral artery is an important cause of posterior circulation stroke. Endovascular stenting has shown promise for these lesions, but evidence in patients aged ≥ 70 years is limited. This study assessed perioperative safety and intermediate-term efficacy of extracranial vertebral artery stenting in elderly patients (≥70 years) by comparing rates of complications, restenosis, stroke, and death with those in younger patients.

Methods: We retrospectively analyzed patients with symptomatic extracranial vertebral artery stenosis (VAS) treated at our center from 2019 to 2024. Patients were divided into two groups (≥70 vs. <70 years). All patients had failed medical therapy (antiplatelet ± statin) and underwent stent placement. We compared perioperative adverse events, in-stent restenosis (ISR), target-vessel stroke, and any stroke or death between groups.

Results: Among 224 patients (93 aged ≥ 70, 131 aged < 70), technical success was 100%. Median age was 74 (IQR 72-77) in the ≥70 group and 63 (IQR 59-66) in the <70 group. Perioperative complication rates did not differ significantly (4.3% vs. 3.1%; p = 0.721). Over a mean follow-up of 15 months, ISR occurred in 13.5% of ≥70 patients and 17.6% of <70 patients (p = 0.50), and target-vessel stroke occurred in 3.3% vs. 1.6% (p > 0.05). Multivariate analysis showed that bare-metal stent use and hyperuricemia independently predicted ISR. However, the combined outcome of any stroke or death was significantly higher in the ≥70 group than in the <70 group (14.6% vs. 3.2%, log-rank p < 0.05), which was largely attributed to more severe atherosclerosis and a higher burden of comorbidities in the older population.

Conclusion: In symptomatic patients with extracranial VAS, endovascular stenting in the elderly (≥70 years) appears comparably safe to younger patients, with similarly low restenosis and target-stroke rates. Use of bare-metal stents and hyperuricemia were associated with higher ISR. These findings support considering vertebral stenting in elderly patients, but emphasize the need for close follow-up.

Background and purpose: The Endothelial Activation and Stress Index (EASIX) is a marker of endothelial dysfunction. This study aimed to explore the association between the EASIX score and unfavorable outcome in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT) treatment.

Methods: We enrolled AIS patients treated with MT from a multicenter study between June 2021 to September 2024. The EASIX score was calculated as lactate dehydrogenase (LDH) (U / L) × Creatinine (mg / dL) / Platelet Count (10 ^∧ 9 / L). The unfavorable outcome was defined as 90-day modified Rankin scale score 3-6. We used multivariable logistic regression models to investigate the association between EASIX score and unfavorable outcome. A restricted cubic spline analysis was conducted to describe the linear relationship between the EASIX score and unfavorable outcome.

Results: A total of 406 patients (258 [63.5%] male and median age: 71 years) were included in this study. 181 (44.6%) patients experienced unfavorable outcome. The logistic regression models demonstrated a robust association between the EASIX score and unfavorable outcome (log2 transformed odds ratio [OR]: 1.41; 95% confidence interval [CI]: 1.19-1.70; P < 0.001; tertile 3 vs. tertile 1 OR: 2.05; 95% CI: 1.14-3.55; P = 0.017). The restricted cubic spline analysis revealed a linearly increasing association between the EASIX score and the risk of unfavorable outcome (P for nonlinearity = 0.802).

Conclusion: Higher EASIX levels were significantly related to unfavorable outcome in AIS patients treated with MT. EASIX score may serve as a valuable tool for early risk assessment and outcome prediction in AIS patients.

Alzheimer's disease (AD), a neurodegenerative disorder, significantly impacts patients, families, and society. Therefore, efficient AD diagnosis and disease analysis are crucial. Electroencephalogram (EEG) directly reflects brain activity, making EEG-based AD identification a current research hotspot. This review utilized digital libraries (Google Scholar and PubMed) to categorize the literature into two sets based on different periods, ultimately analyzing the application of EEG in AD research through 141 articles after screening. Critical topics addressed include subject types, experimental design, electrode selection, artifact processing, rhythm division, feature extraction, recognition methods, etc. Additionally, the review discusses major conclusions, emphasizing research priorities and consistent findings. The study also briefly mentions other biomarkers and predicts future trends of EEG as a biomarker. This work provides valuable references for researchers and clinicians exploring the relationship between EEG and AD.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/.