Frontiers in Aging Neuroscience最新文献

Objective: To investigate the bidirectional relationship between depression and activities of daily living (ADL) in Parkinson's disease (PD) patients and explore the mediating role of cognitive function over time.

Methods: Data from 892 PD patients from the Parkinson's Progression Markers Initiative (PPMI) database were included in this study, and depression, cognitive function, and ADL were measured using the Geriatric Depression Scale (GDS-15), Montreal Cognitive Assessment Scale (MoCA), and Unified Parkinson's Disease Rating Scale, Part II (UPDRS II) respectively. The cross-lagged panel model (CLPM) was employed to analyze the reciprocal relationship between depression and ADL. Then, we explored the mediating role of cognitive function in the bidirectional relationship between depression and ADL in patients with PD, and the mediation effect test was carried out using a bias-corrected nonparametric percentile bootstrap approach.

Results: Depression in patients with PD predicted their subsequent ADL (β = 0.079, p < 0.01), and ADL also predicted their subsequent depression (β = 0.069, p < 0.05), In addition, Bootstrap analysis showed that cognitive function played a significant mediating role in prediction of depression to ADL in patients with PD (β = 0.006, p = 0.074, 95%CI = 0.001 ~ 0.014), and cognitive function also played a significant mediating role in prediction of depression to ADL (β = 0.006, p = 0.067, 95%CI = 0.001 ~ 0.013).

Conclusion: There is a bidirectional relationship between depression and ADL in patients with PD. Furthermore, we found that cognitive function mediates the relationship that exists between depression and ADL in patients with PD. Interventions aimed at enhancing cognitive function could potentially lessen the vicious cycle of depression and ADL in PD, thus improving patient quality of life (QOL).

Objective: The 2024 Alzheimer's Association (AA) research diagnostic criteria for Alzheimer's Disease (AD) considers fluid biomarkers, including promising blood-based biomarkers for detecting AD. This study aims to identify dementia subtypes and their cognitive and neuroimaging profiles in older adults with dementia in the Democratic Republic of Congo (DRC) using biomarkers and clinical data.

Methods: Forty-five individuals with dementia over 65 years old were evaluated using the Community Screening Instrument for Dementia and the informant-based Alzheimer's Questionnaire. Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood plasma. Neuroimaging structures were assessed using magnetic resonance imaging (MRI). Dementia subtypes were determined based on plasma biomarker pathology and vascular markers. Biomarker cutoff scores were identified to optimize sensitivity and specificity. Individuals were stratified into one of four dementia subtypes-AD only, non-AD vascular, non-AD other, or mixed - based on combinations of abnormalities in these markers.

Results: Among the 45 individuals with dementia, mixed dementia had the highest prevalence (42.4%), followed by AD-only (24.4%), non-AD other dementia (22.2%), and non-AD vascular dementia subtypes (11.1%). Both cognitive and neuroimaging profiles aligned poorly with biomarker classifications in the full sample. Cognitive tests varied across dementia subtypes. The cognitive profile of the AD-only and mixed groups suggested relatively low cognitive performance, while the non-AD and other groups had the best scores on average.

Conclusion: Consistent with studies in other settings, our preliminary findings suggest that neurodegenerative plasma biomarkers may help to identify dementia subtypes and provide insight into cognitive and neuroimaging profiles among older adults in the DRC.

Objectives: To propose a multimodal functional brain network (FBN) and structural brain network (SBN) topological feature fusion technique based on resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), 3D-T1-weighted imaging (3D-T1WI), and demographic characteristics to diagnose mild cognitive impairment (MCI) in patients with unilateral middle cerebral artery (MCA) steno-occlusive disease.

Methods: The performances of different algorithms on the MCI dataset were evaluated using 5-fold cross-validation. The diagnostic results of the multimodal performance were evaluated using t-distributed stochastic neighbor embedding (t-SNE) analysis. The four-modal analysis method proposed in this study was applied to identify brain regions and connections associated with MCI, thus confirming its validity.

Results: Based on the fusion of the topological features of the multimodal FBN and SBN, the accuracy for the diagnosis of MCI in patients with unilateral MCA steno-occlusive disease reached 90.00%. The accuracy, recall, sensitivity, and F1-score were higher than those of the other methods, as was the diagnostic efficacy (AUC = 0.9149).

Conclusion: The multimodal FBN and SBN topological feature fusion technique, which incorporates rs-fMRI, DTI, 3D-T1WI, and demographic characteristics, obtains the most discriminative features of MCI in patients with unilateral MCA steno-occlusive disease and can effectively identify disease-related brain areas and connections. Efficient automated diagnosis facilitates the early and accurate detection of MCI and timely intervention and treatment to delay or prevent disease progression.

Background: Animal models of Alzheimer's disease (AD) are essential tools for investigating disease pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal and glial alterations in the hippocampus and medial prefrontal cortex (mPFC) of young TgF344-AD rats and correlated these changes with cognitive decline and amyloid-β plaque load.

Methods: We compared TgF344-AD and non-transgenic littermate rats aged 7-8 months of age. We systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes of GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, and somatostatin-positive neurons), and newly generated neurons in the hippocampus. Spatial learning and memory were assessed using the Barnes maze test.

Results: Young TgF344-AD rats had a large number of amyloid plaques in both the hippocampus and mPFC, together with a pronounced increase in microglial cell numbers. Astrocytic activation was significant in the mPFC. Cholecystokinin-positive cell numbers were decreased in the hippocampus of transgenic rats, but calretinin-, parvalbumin-, and somatostatin-positive cell numbers were not altered. Adult neurogenesis was not affected by genotype. TgF344-AD rats had spatial learning and memory impairments, but this cognitive deficit did not correlate with amyloid plaque number or cellular changes in the brain. In the hippocampus, amyloid plaque numbers were negatively correlated with cholecystokinin-positive neuron and microglial cell numbers. In the mPFC, amyloid plaque number was negatively correlated with the number of astrocytes.

Conclusion: Pronounced neuropathological changes were found in the hippocampus and mPFC of young TgF344-AD rats, including the loss of hippocampal cholecystokinin-positive interneurons. Some of these neuropathological changes were negatively correlated with amyloid-β plaque load, but not with cognitive impairment.

Background: Alzheimer's disease (AD) might be best conceptualized as a disconnection syndrome, such that symptoms may be largely attributable to disrupted communication between brain regions, rather than to deterioration within discrete systems. EEG is uniquely capable of directly and non-invasively measuring neural activity with precise temporal resolution; connectivity quantifies the relationships between such signals in different brain regions. EEG research on connectivity in AD and mild cognitive impairment (MCI), often considered a prodromal phase of AD, has produced mixed results and has yet to be synthesized for comprehensive review. Thus, we performed a systematic review of EEG connectivity in MCI and AD participants compared with cognitively healthy older adult controls.

Methods: We searched PsycINFO, PubMed, and Web of Science for peer-reviewed studies in English on EEG, connectivity, and MCI/AD relative to controls. Of 1,344 initial matches, 124 articles were ultimately included in the systematic review.

Results: The included studies primarily analyzed coherence, phase-locked, and graph theory metrics. The influence of factors such as demographics, design, and approach was integrated and discussed. An overarching pattern emerged of lower connectivity in both MCI and AD compared to healthy controls, which was most prominent in the alpha band, and most consistent in AD. In the minority of studies reporting greater connectivity, theta band was most commonly implicated in both AD and MCI, followed by alpha. The overall prevalence of alpha effects may indicate its potential to provide insight into nuanced changes associated with AD-related networks, with the caveat that most studies were during the resting state where alpha is the dominant frequency. When greater connectivity was reported in MCI, it was primarily during task engagement, suggesting compensatory resources may be employed. In AD, greater connectivity was most common during rest, suggesting compensatory resources during task engagement may already be exhausted.

Conclusion: The review highlighted EEG connectivity as a powerful tool to advance understanding of AD-related changes in brain communication. We address the need for including demographic and methodological details, using source space connectivity, and extending this work to cognitively healthy older adults with AD risk toward advancing early AD detection and intervention.

Background: This study evaluates the impact of ultrasound-guided stellate ganglion block (SGB) on early postoperative cognitive dysfunction (POCD) in elderly patients who underwent laparoscopic gastrointestinal (GI) surgery, as well as its potential effect on oxidative stress and inflammatory responses.

Methods: In this randomized controlled trial, 104 elderly patients scheduled for elective laparoscopic GI surgery were randomized to receive ultrasound-guided SGB before general anesthesia (SGB group) or general anesthesia alone (control group). A total of 98 patients completed the study. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) preoperatively, and on postoperative days one and three. The perioperative recordings included mean arterial pressure, heart rate, and the bispectral index. Blood samples were analyzed for interleukin-6 (IL-6), superoxide dismutase (SOD), and malondialdehyde (MDA).

Results: The SGB group had a significantly lower incidence of POCD on postoperative day one (p < 0.05). IL-6 and MDA levels were significantly lower, while SOD levels were higher in the SGB group, when compared to the control group (p < 0.05). MDA levels were notably lower on postoperative day three in the SGB group (p < 0.05). Both groups showed significant changes in IL-6, SOD and MDA levels, when compared to preoperative values. The hemodynamic indicators showed a slight reduction in intraoperative blood pressure and decreased numerical rating scale scores on the first postoperative day without significant differences in other indicators.

Conclusion: Preoperative SGB reduces early POCD in elderly patients who undergo laparoscopic GI surgery, possibly through the inhibition of oxidative stress and inflammatory responses.

Background: The excitatory imbalance of glutamatergic neurons, caused by insufficient input from dopaminergic neurons, contributes the pathogenesis of Parkinson's disease (PD). Exercise training is one of the non-pharmacological, non-invasive therapeutic approaches.

Objective: This systematic review is the first to summarize the effects of exercise training on the regulation of protein and gene expressions within the nigrostriatal glutamatergic pathway and its receptor interactions in animal models of Parkinson's disease (PD).

Methodology: The PubMed, Web of Science, and Embase electronic databases were searched, and 9 out of 96 studies that met the PRISMA guidelines were included. These studies received a CAMARADES score ranging from 4 to 6 out of 10. The included studies utilized pharmacologically induced PD models in mice or rats with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA). The majority of studies (89%) employed treadmill training, while 11% used voluntary wheel running, with training protocols consisting of 5 days per week for 4 weeks.

Results: Exercise training reduced extracellular glutamate (Glu) and increased the expression of GLT-1, GS, Gln, and mGluR2/3 while down-regulating VGULT1 in the presynaptic terminal of the glutamatergic neurons within the nigrostriatal pathway in PD animal models. It also downregulated mGluR5 and modulated the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits: GluA1 was downregulated, inhibiting long-term potentiation, while GluA2 and GluA3 were upregulated in the nigrostriatal pathway in PD animal models. In addition, the exercise training downregulated the N-methyl-D-aspartate (NMDA) receptors, Arc, Cav1.3, CaMKII, and p-CaMKII in the nigrostriatal pathway in PD animal models.

Conclusion: Exercise training exerted a neuroprotective effect on the glutamatergic pathway in Parkinson's disease (PD) animal models by limiting excess glutamate in the synaptic cleft. Exercise training modulated the ionotropic receptors and limited the glutamatergic excitatory imbalance within the nigrostriatal pathway in PD animal models. It also improved motor function, including balance, coordination, and gait parameters.

Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024564127.

The underlying neuropathological mechanisms in Binswanger's disease (BD) with mild cognitive impairment (BD-MCI) remain unclear. The multiparameter functional magnetic resonance imaging (fMRI) including amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), independent component analysis (ICA), and edge-link analysis was utilized to explore the abnormal brain networks of BD-MCI patients. Compared with the BD without MCI group, this study revealed that the ALFF values in the BD-MCI group were significantly increased in the Temporal_Inf_R, Frontal_Mid_Orb_L, and Hippocampus_L, while decreased in the SupraMarginal_R and Precuneus_R. The fALFF value in the BD-MCI group exhibited a reduction in the Frontal_Med_Orb_L. Additionally, ReHo values in the BD-MCI group increased in the Hippocampus_R but decreased in several areas including Precentral_L, Putamen_L, Postcentral_R, Supp_Motor_Area_R, and SupraMarginal_L. The results of ICA revealed that patients diagnosed with BD-MCI exhibited abnormal connectivity patterns across 12 groups of independent components and 5 distinct groups of brain networks. In one group, the internal connectivity within the brain network exhibited abnormalities. The correlation analysis between ALFF and ReHo values and clinical scales revealed a significant negative correlation between the bilateral hippocampus and Mini-Mental State Examination (MMSE) scores. Conversely, ReHo values for Postcentral_R and SupraMarginal_L were significantly positively correlated with MMSE scores. In summary, the results of our study suggest that patients diagnosed with BD-MCI display atypical activity across several brain regions. The observed changes in these areas encompass a range of functional networks. The reduced coordination among these functional networks may play a role in the deterioration of cognitive functions and decision-making capabilities, potentially serving as a critical mechanism contributing to the early manifestation of cognitive impairments.

Alzheimer's disease (AD) is a complex neurocognitive disorder. Early theories of AD sought to identify a single unifying explanation underlying AD pathogenesis; however, evolving evidence suggests it is a multifactorial, systemic disease, involving multiple systems. Of note, vascular dysfunction, encompassing both cerebral and peripheral circulation, has been implicated in AD pathogenesis. This pilot study used intravital microscopy to assess differences in responsiveness of gluteal muscle arterioles between a transgenic AD mouse model (APP/PS1; Tg) and wild-type (C57BL/6; WT) mice to further elucidate the role of vascular dysfunction in AD. Arteriole diameters were measured in response to acetylcholine (10^-9 to 10^-5 M), phenylephrine (10^-9 to 10^-5 M), histamine (10^-9 to 10^-4 M) and compound 48/80 (10^-9 to 10^-3 M). Tg mice demonstrated a trend toward reduced vasodilatory response to acetylcholine with a significant difference at 10^-5 M (36.91 vs. 69.55%: p = 0.0107) when compared to WT. No significant differences were observed with histamine, compound 48/80 or phenylephrine; however, a trend toward reduced vasoconstriction to phenylephrine was observed in Tg mice at higher concentrations. Mean net diameter change (resting to maximum) also differed significantly (p = 0.0365) between WT (19.11 μm) and Tg mice (11.13 μm). These findings suggest reduced vascular responsiveness may contribute to the systemic vascular deficits previously observed in AD models. Future research using diverse models and broader variables could further elucidate peripheral vascular dysfunction's role in AD pathogenesis, including its impact on motor symptoms and disease progression. Such insights may inform the development of vascular-targeted therapeutic strategies.