Frontiers in Aging Neuroscience最新文献

Background: The number of patients with cerebral small vessel disease is increasing, especially among the elderly population. With the continuous improvement of detection techniques, the positivity rate keeps increasing. Our goal is to develop a nomogram for early identification of PSCI and PSCID in stroke patients.

Methods: In a retrospective cohort, chained data imputation was performed to ensure no statistical differences from the original dataset. Subsequently, Boruta algorithm was utilized for variable selection based on their importance, followed by logistic regression employing backward stepwise regression. Finally, the regression results were visualized as a Nomogram.

Results: The nomogram chart in this study achieves clinical utility in a concise and user-friendly manner, passing the Hosmer-Lemeshow goodness-of-fit test. ROC and calibration curves indicate its high discriminative ability.

Conclusion: While CSVD is prevalent among middle-aged and older individuals, cognitive decline trajectories differ. Endocrine metabolic indicators like IGF-1 offer early predictive value. This study has produced a succinct nomogram integrating demographic and clinical indicators for medical application.

Ketamine has received growing attention for its effects on neuroplasticity and neuroinflammation, and as a treatment for depression and other mental health disorders. Recent evidence suggests that early sensory and behavioral deficits in Alzheimer's disease could be caused by synaptic disruption that occurs before irreversible neuropathology. This raises the possibility that ketamine could slow down or prevent network disruption and the ensuing sensory and behavioral deficits in Alzheimer's. Here we tested this idea in the 5XFAD mouse model of Alzheimer's, using either an acute single injection of ketamine, or chronic daily injections over 15 weeks. We tested the effects of ketamine on both amyloid plaque load and on a behavioral auditory gap detection task that is an early Alzheimer's biomarker in both mice and humans. We found that ketamine had no effect on plaque load, nor any effect on gap detection, for either acute or chronic dosing. Chronic ketamine facilitated startle responses specifically in 5XFAD mice, but this could simply be related to experience-dependent effects on stress or habituation rather than any rescue effect of ketamine on Alzheimer's-related deficits. We did find robust correlations between gap detection deficits and plaque load in auditory cortex and in the caudal pontine reticular nucleus, demonstrating that the behavioral deficits seen in 5XFAD mice are directly related to amyloid accumulation in these brain regions, and confirming the validity of gap detection as an early biomarker of Alzheimer's. Ketamine, however, had no effect on the strength of these correlations. We conclude that ketamine has no beneficial effect on the development of behavioral gap detection deficits or plaque load in the 5XFAD Alzheimer's mouse model, following either an acute single dose or a chronic daily dose regimen.

Objective: To explore MRI-based radiomics models, integrating clinical characteristics, for differential diagnosis of Parkinson's disease (PD) to evaluate their diagnostic performance.

Methods: A total of 256 participants [153 PD, 103 healthy controls (HCs)] from the First Affiliated Hospital of Wenzhou Medical Hospital, were enrolled as the training set, and 120 subjects (74 PD, 46 HCs) from the PPMI dataset served as the test set. Radiomics features were extracted from structural MRI (T1WI and T2-FLair). Support Vector Machine (SVM) classifiers were developed using MRI radiomics data from both monomodal and multimodal radiomics models. The clinical-radiomics model was constructed by integrating clinical variables, including UPDRS, Hoehn-Yahr stage, age, sex, and MMSE scores. Receiver operating characteristic (ROC) curves were generated to evaluate the performance of the models. Decision curve analysis (DCA) was performed to access the clinical usefulness of the models.

Results: In the training set, the T2-FLair and T1WI radiomics model achieved an AUC of 0.896 (95% CI, 0.812-0.900) and 0.899 (95% CI, 0.818-0.908), respectively. The double-sequence radiomics model demonstrated superior diagnostic performance, with an AUC of 0.965 (95% CI, 0.885-0.978) in the training set and an AUC of 0.852 (95% CI, 0.748-0.910) in the test set. The integrated clinical-radiomics model showed enhanced diagnostic accuracy, with AUC = 0.983 (95% CI, 0.897-0.996) in the training set and AUC = 0.837 (95% CI, 0.786-0.902) in the test set. Rad-scores derived from the radiomics model were significantly correlated with diagnostic outcomes (P < 0.001). DCA confirmed the substantial clinical usefulness of the clinical-radiomics integrated model.

Conclusion: The integrated clinical-radiomics model offered superior diagnostic performance compared to models based relying solely on imaging or clinical data, underscoring its potential as a non-invasive and effective tool in routine clinical practice for the early diagnosis of PD.

Background: Obesity exerts a significant detrimental impact on cognitive function. The weight-adjusted waist index (WWI) serves as a more precise indicator of visceral obesity that is independent of weight, in contrast to body mass index (BMI). Still, little research has been conducted on the interrelation between WWI and cognitive abilities. This investigation explored the link between WWI and older Americans' cognitive function.

Methods: Utilizing data from the 2011-2014 National Health and Nutrition Examination Cross-Sectional Survey, multiple linear regression analysis was used to assess the influence of WWI on cognitive abilities in those over 60. Three cognitive assessments were administered: the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), and the Word Learning and Recall Module from the Coalition to Establish a Registry for Alzheimer's Disease (CERAD). We implemented threshold effects analysis and smoothed curve fitting to elucidate the nonlinear relationship. Additionally, we analyzed subgroups to check for variability.

Results: There were 2,762 participants, including1,504 (54.45%) females and 1,258 (45.55%) males. 53.77% of them had completed high school or above, and their average age was 69.05 ± 6.62. After controlling for confounding variables, the improved model predicted a negative connection between WWI and CERAD-Total, AFT, and DSST scores (all p < 0.05). Furthermore, we performed a smoothenable curve fitting between WWI and cognitive function scores, resulting in a nonlinear connection and a threshold saturation effect. We also executed subgroup analyses and interaction tests based on gender, race, educational background, marital status, diabetes, body mass index, alcohol consumption, hypertension, smoking habits, stroke, depression, and sleep quality to assess whether the relationship between WWI and cognitive function was affected by heterogeneity across different population segments. The subgroup analysis found no significant differences in cognitive performance associated with WWI across the various subgroups.

Conclusion: Higher WWI levels are associated with impaired cognitive function in Americans aged 60 and older.

[This corrects the article DOI: 10.3389/fnagi.2024.1444703.].

Introduction: This systematic review and meta-analysis aimed to compare the efficacy of extended supplementation (≥6 weeks) with natural compounds or extracts in improving cognitive function in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD).

Methods: A comprehensive literature search was conducted across Cochrane, PubMed, PsycARTICLES, Scopus, and Web of Science databases from inception to April 10, 2024. Eligible studies were randomized controlled trials evaluating cognitive outcomes in patients with MCI or AD using the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).

Results: From an initial pool of 6,687 articles, 45 were deemed relevant for qualitative analysis. Of these, 37 studies demonstrated improvements or positive trends in cognitive outcomes with natural compound or extract supplementation. A total of 35 studies met the criteria for meta-analysis. The meta-analysis, involving 4,974 participants, revealed significant improvements in ADAS-Cog scores (pooled standardized mean difference = -2.88, 95% confidence interval [CI]: -4.26 to -1.50; t₂₄ = -4.31, p < 0.01) following supplementation. Additionally, a suggestive trend toward improvement in MMSE scores was observed in a subgroup analysis of 1,717 participants (pooled standardized mean difference = 0.76, 95% CI: 0.06 to 1.46, t₁₈ = 2.27, p = 0.04).

Conclusion: These findings support the potential cognitive benefits of extended (≥6 weeks) supplementation with natural compounds or extracts in individuals with MCI or AD. Further research is warranted to confirm these results and elucidate the underlying mechanisms.

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

Introduction: This study aims to assess the pattern of functional connectivity (FC) between cerebellar subregions, the basal ganglia (BG), and the cortex, and explore the relationship between FC patterns and cognitive function after stroke with BG infarcts.

Methods: A total of 39 stroke patients and 29 healthy controls were recruited. Four cerebellar seed points were selected, and the FC of each seed point with other voxels in the whole brain was calculated. FC and cognitive performance were compared between the two groups, and their correlations were analyzed.

Results: Stroke patients exhibited increased FC between the bilateral cerebellum IX and BG (particularly the head of the caudate nucleus), which was positively correlated with episodic memory, visuospatial ability, and attention. Increased FC was also observed between the right cerebellum Crus I/II and BG, as well as the bilateral cerebellum VI and BG, correlating positively with episodic memory. Conversely, decreased FC was identified between the bilateral cerebellum IX and the right caudal cuneus, which negatively correlated with episodic memory, language, and attention but positively correlated with executive function. Additionally, increased FC between the bilateral cerebellum VI and the bilateral inferior parietal lobule was associated with improvements in episodic memory, language, and attention. Decreased FC was observed between the right cerebellum VI and the left insula, as well as between the right cerebellum Crus I/II and the left insula, which negatively correlated with episodic memory.

Discussion: The enhanced FC between the cerebellum and BG, along with the reorganization of new neural circuits involving the cerebellar cortex, may contribute to cognitive recovery following stroke. These changes may represent compensatory mechanisms of the cerebellum in response to stroke injury.

Introduction: Many predictive models for cognitive impairment after mild stroke and transient ischemic attack are based on cognitive scales at a certain timepoint. We aimed to develop two easy-to-use predictive models based on longitudinal cognitive trajectories to facilitate early identification and treatment.

Methods: This was a prospective cohort study of 556 patients, followed up every 3 months. Patients with at least two cognitive scales within 2.5 years were included in the latent class growth analysis (LCGA). The patients were categorized into two groups based on the LCGA. First, a difference analysis was performed, and further univariate and stepwise backward multifactorial logistic regression was performed. The results were presented as nomograms, and receiver operating characteristic curve analysis, calibration, decision curve analysis, and cross-validation were performed to assess model performance.

Results: The LCGA eventually included 255 patients, and the "22" group was selected for further subgroup analysis. Among them, 29.8% were included in the cognitive impairment trajectory. Model 1, which incorporated baseline Montreal Cognitive Assessment, ferritin, age, and previous stroke, achieved an area under the curve (AUC) of 0.973, and model 2, which incorporated age, previous stroke, education, and ferritin, with an AUC of 0.771. Decision curve analysis and cross-validation showed excellent clinical applicability.

Discussion: Here, we developed two simple and easy-to-use predictive models of post-stroke cognitive trajectories based on a LCGA, which are presented in the form of nomograms suitable for clinical application. These models provide a basis for early detection and prompt treatment.

Objective: The aim of this study was to compare the efficacy and safety of anti-tau protein monoclonal antibodies for Alzheimer's disease (AD). Tau protein aggregation, a key pathological feature of AD, is closely associated with neurodegeneration and cognitive decline. Targeting tau protein has emerged as a promising therapeutic strategy. By investigating the effects of monoclonal antibodies on cognitive function, disease progression, and overall quality of life in patients with AD, which can provide valuable insights into their potential as a therapeutic option for this devastating neurodegenerative disorder.

Methods: The randomized controlled trials (RCTs) investigating the efficacy of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in Alzheimer's disease (AD) were systematically searched across PubMed, Embase, Web of Science and Cochrane Library, up to May 2024. The control group included placebo. The efficacy indicators were change in the Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) from baseline until the time of efficacy observation. Statistical analysis was conducted using Stata 14 and RevMan 5.4. The purpose of data processing, including generating network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots, and funnel plots, is to visually summarize and evaluate the relative effectiveness and safety and potential publication bias of multiple interventions. Mean differences (MD) and 95% confidence interval (95%CI) as effect sizes to analyze continuous variables.

Results: This study encompassed six RCTs involving 2,193 patients. Semorinemab were more effective than placebo in MMSE and ADAS-Cog scores (MDs ranging between 0.52 and 3.21; MDs ranging between 0.17 and 3.30). Placebo showed relatively good efficacy according to SUCRA ranking on change in CDR-SB and ADCS-ADL scores (75.7 and 79.5%). Tilavonemab and Semorinemab exhibited efficacy similar to that of a placebo in the analysis of the two indicators. Tilavonemab showed a lower incidence of AE, SAE, fall, and urinary tract infections than placebo, and the differences were statistically significant. Most safety analysis results showed no statistical difference.

Conclusion: The results indicated that anti-tau protein monoclonal antibodies, such as Semorinemab and Tilavonemab, showed promise in terms of efficacy and safety for managing AD. Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols.

Systematic review registration: https://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388.

The discovery of hypoxic pockets within the cortical regions has transformed the understanding of cerebral oxygen dynamics, revealing their dual role as both contributors to neuronal adaptation and potential precursors to dysfunction. These transient oxygen-deprived microenvironments play a pivotal role in neurovascular coupling, synaptic plasticity, and angiogenesis, processes crucial for maintaining cognitive resilience and neuronal health. Investigating hypoxic pockets within cortical regions is particularly relevant in aging populations and individuals with neurodegenerative conditions. Concurrently, research underscores the ability of physical, social, and cognitive activities to modulate brain oxygenation, offering natural, accessible interventions to optimize oxygen delivery and utilization. This study synthesizes findings from neuroimaging, behavioral science, and longitudinal studies, illustrating how daily routines can mitigate hypoxia-induced cognitive decline and promote resilience. By integrating insights from centenarians, hypoxia-adapted species, and multimodal intervention studies, this framework highlights the transformative potential of lifestyle-based strategies in addressing cerebral oxygen deficits. The findings advocate for an interdisciplinary approach to develop targeted interventions for public health, rehabilitation, and personalized cognitive care.