Frontiers in Aging Neuroscience最新文献

Background: Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted.

Results: The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI.

Conclusion: The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Objective: To evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community.

Methods: In the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline.

Results: A total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups (p < 0.05). The top three eye-tracking paradigms were anti-saccade, gap saccade, and median fixation, with AUCs of 0.911, 0.904, and 0.891, respectively. The gait analysis features had an AUC of 0.862, indicating better discriminatory efficacy compared to the SCD9 scale, which had an AUC of 0.762. The model based on single and dual task gait, anti-saccade, gap saccade, and median fixation achieved the best efficacy in SCD screening (AUC = 0.969).

Conclusion: The gait analysis, eye-tracking multimodal assessment tool is an objective and accurate screening method that showed better detection of subjective cognitive decline. This finding provides another option for early identification of subjective cognitive decline in the community.

[This corrects the article DOI: 10.3389/fnagi.2024.1419253.].

Background: Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson's disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson's disease still remain elusive.

Methods: This study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics.

Results: We discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores.

Conclusion: Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients.

Background: Neuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer's disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1β, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1β and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases.

Methods: In this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1β secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in full-body Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays.

Results: Activation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines.

Conclusion: The absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors.

Background: Hypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies.

Methods: In this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate.

Results: The mean velocity of the COP in the medial-lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p < 0.001).

Conclusion: The standing balance function of older adults with HT does not appear to be worse based on COP parameters than those of older adults with NT. This study revealed that the changes in the central cortex related to standing balance appear to be more indicative of balance control deficits in older adults with HT than changes in peripheral COP parameters, suggesting the importance of the early evaluation of cortical activation in older adults with HT at risk of falls.

Introduction: Research has shown that speech analysis demonstrates sensitivity in detecting early Alzheimer's disease (AD), but the relation between linguistic features and cognitive tests or biomarkers remains unclear. This study aimed to investigate how linguistic features help identify cognitive impairments in patients in the early stages of AD.

Method: This study analyzed connected speech from 80 participants and categorized the participants into early-AD and normal control (NC) groups. The participants underwent amyloid-β positron emission tomography scans, brain magnetic resonance imaging, and comprehensive neuropsychological testing. Participants' speech data from a picture description task were examined. A total of 15 linguistic features were analyzed to classify groups and predict cognitive performance.

Results: We found notable linguistic differences between the early-AD and NC groups in lexical diversity, syntactic complexity, and language disfluency. Using machine learning classifiers (SVM, KNN, and RF), we achieved up to 88% accuracy in distinguishing early-AD patients from normal controls, with mean length of utterance (MLU) and long pauses ratio (LPR) serving as core linguistic indicators. Moreover, the integration of linguistic indicators with biomarkers significantly improved predictive accuracy for AD. Regression analysis also highlighted crucial linguistic features, such as MLU, LPR, Type-to-Token ratio (TTR), and passive construction ratio (PCR), which were sensitive to changes in cognitive function.

Conclusion: Findings support the efficacy of linguistic analysis as a screening tool for the early detection of AD and the assessment of subtle cognitive decline. Integrating linguistic features with biomarkers significantly improved diagnostic accuracy.

Background: Working memory (WM) loss, which can lead to a loss of independence, and declines in the quality of life of older adults, is becoming an increasingly prominent issue affecting the ageing population. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is emerging as a potential alternative to pharmacological treatments that shows promise for enhancing WM capacity and May enhance the effects of cognitive training (CT) interventions.

Objective: The purpose of this meta-analysis was to explore how different tDCS protocols in combination with CT enhanced WM in healthy older adults.

Methods: Randomized controlled trials (RCTs) exploring the effects of tDCS combined with CT on WM in healthy older adults were retrieved from the Web of Science, PubMed, Embase, Scopus and the Cochrane Library databases. The search time period ranged from database inception to January 15, 2024. Methodological quality of the trials was assessed using the risk-of-bias criteria for RCTs from the Cochrane Collaboration Network, and RevMan 5.3 (Cochrane, London, United Kingdom) was used for the meta-analysis of the final literature outcomes.

Results: Six RCTs with a total of 323 participants were ultimately included. The results of the meta-analysis show that tDCS combined with CT statistically significantly improves WM performance compared to the control sham stimulation group in healthy older adults [standard mean difference (SMD) = 0.35, 95% CI: 0.11-0.59, I ² = 0%, Z = 2.86, p = 0.004]. The first subgroup analysis indicated that, when the stimulus intensity was 2 mA, a statistically significant improvement in WM performance in healthy older adults was achieved (SMD = 0.39, 95% CI: 0.08-0.70, I ² = 6%, Z = 2.46, p = 0.01). The second subgroup analysis showed that long-term intervention (≥ 10 sessions) with tDCS combined with CT statistically significantly improved WM compared to the control group in healthy older adults (SMD = 0.72, 95% CI: 0.22-1.21, I ² = 0%, Z = 2.85, p = 0.004).

Conclusion: tDCS combined with CT statistically significantly improves WM in healthy older adults. For the stimulus parameters, long-term interventions (≥ 10 sessions) with a stimulation intensity of 2 mA are the most effective.

Objective: This study investigates the causal relationship between moderate to vigorous physical activity and cognitive performance.

Methods: Genetic loci strongly related to moderate to vigorous physical activity from genome-wide association studies were used as instrumental variables. These were combined with genetic data on cognitive performance from different Genome-Wide Association Study (GWAS) to conduct a two-sample Mendelian randomization analysis. The primary analysis used inverse variance weighting within a random effects model, supplemented by weighted median estimation, MR-Egger regression and other methods, with results expressed as Beta coefficient.

Results: This study selected 19 SNPs closely related to physical activity as instrumental variables. The multiplicative random-effects Inverse-Variance Weighted (IVW) analysis revealed that moderate to vigorous physical activity was negatively associated with cognitive performance (Beta = -0.551; OR = 0.58; 95% CI: 0.46-0.72; p < 0.001). Consistent results were obtained using the fixed effects IVW model (Beta = -0.551; OR = 0.58; 95% CI: 0.52-0.63; p < 0.001), weighted median (Beta = -0.424; OR = 0.65; 95% CI: 0.55-0.78; p < 0.001), simple mode (Beta = -0.467; OR = 0.63; 95% CI: 0.44-0.90; p < 0.001), and weighted mode (Beta = -0.504; OR = 0.60; 95% CI: 0.44-0.83; p < 0.001). After adjusting for BMI, smoking, sleep duration, and alcohol intake frequency, the multivariate MR analysis also showed a significant association between genetically predicted MVPA and cognitive performance, with Beta of -0.599 and OR = 0.55 (95% CI: 0.44-0.69; p < 0.001).

Conclusion: The findings of this study indicate that genetically predicted moderate to vigorous physical activity may be associated with a decline in cognitive performance.

Objective: This study aims to investigate the relationship between muscle strength, working memory, and activities of daily living (ADL) in older adults. Additionally, it seeks to clarify the pathways and effects of working memory in mediating the relationship between muscle strength and ADL.

Methods: Using a cross-sectional study design, we recruited 245 older adults individuals from nursing homes. We collected data on grip strength, the 30-s sit-to-stand test, the N-back task, and ADL. The data were analyzed using independent sample t-tests, χ2 tests, correlation analysis, and structural equation modeling.

Results: Grip strength significantly influenced ADL (effect size = -0.175, 95% CI: -0.226 to -0.124). Grip strength also had a significant direct effect on ADL (effect size = -0.114, 95% CI: -0.161 to -0.067). The 1-back task correct rate significantly mediated the relationship between grip strength and ADL (effect size = 0.054, 95% CI: -0.084 to -0.029). The 30-s sit-to-stand test significantly impacted ADL (effect size = -0.280, 95% CI: -0.358 to -0.203). It also had a significant direct effect on ADL (effect size = -0.095, 95% CI: -0.183 to -0.007). The 1-back task correct rate significantly mediated the relationship between the 30-s sit-to-stand test and ADL (effect size = -0.166, 95% CI: -0.236 to -0.106).

Conclusion: There exists a strong correlation between muscle strength, working memory, and ADL. Increased muscle strength leads to better ADL performance and improved working memory tasks. Low cognitive load working memory tasks can mediate the relationship between muscle strength and ADL. Regular physical exercise can enhance muscle strength, slow down the decline of working memory, thereby maintaining or improving ADL in older adults.