Frontiers in Aging Neuroscience最新文献

Advanced aging is associated with robust changes in neural activity. In addition to the well-established age-related slowing of the peak alpha frequency, there is a growing body of evidence showing that older age is also associated with changes in alpha power and beta power. Despite the important progress that has been made, the interacting effects of age and frequency band have not been directly tested in sensor and source space while controlling for aperiodic components. In the current study we address these limitations. We recruited 54 healthy younger and older adults and measured neural oscillations using a high-density electroencephalogram (EEG) system during resting-state with eyes closed. After preprocessing the EEG data and controlling for aperiodic components, we computed alpha and beta power in both sensor and source space. Permutation two-way ANOVAs between frequency band and age group were performed across all electrodes and across all dipoles. Our findings revealed significant interactions in sensorimotor, parietal, and occipital regions. The pattern driving the interaction varied across regions, with older age associated with a progressive decrease in alpha power and a progressive increase in beta power from parietal to sensorimotor regions. Our findings demonstrate that age-related changes in neural oscillations vary as a function of brain region and frequency band. We interpret our findings in the context of clinical and preclinical evidence of age effects on the cholinergic circuit and the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence. This study investigated the association between the American Heart Association's Life's Essential 8 (LE8) and PD prevalence using a large, nationally representative database.

Methods: We analyzed data from 18,277 participants aged 40 years and older from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. LE8 scores were calculated based on diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure. PD cases were identified through self-reported anti-PD medication use. Multivariate logistic regression models were employed to examine the association between LE8 and PD prevalence, adjusting for various demographic and clinical factors. In addition, we performed restricted cubic splines (RCS), subgroup analyses, and weighted quantile sum (WQS) regression to verify the robustness of the study results.

Results: The prevalence of PD was 1.3% in the study population. After full adjustment, individuals with moderate (50-79) and high (80-100) LE8 scores showed lower odds of PD compared to those with low (0-49) scores (OR 0.53, 95% CI 0.29-0.97 and OR 0.43, 95% CI 0.17-1.04, respectively; p for trend <0.05). A dose-response relationship was observed between LE8 scores and PD prevalence. WQS regression identified dietary factors and glycemic health as the main contributors to the inverse association between LE8 and PD.

Conclusion: Our findings suggest a significant inverse association between Life's Essential 8 (LE8) and PD prevalence, with dietary factors and glycemic health emerging as the most influential components.

Objective: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship.

Methods: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships.

Results: We studied 1,207 NOMAS participants (mean age 71 ± 9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia.

Conclusion: Low hematocrit associated with dementia risk in our diverse population cohort. However, our study limitations in laboratory and neuroimaging timing in addition to clarifying mechanistic underpinnings for our observations necessitates further work to clarify whether anemia can serve as a trackable, preventable/treatable risk factor for dementia.

Background: The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer's disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology.

Methods: FMT of bacteria isolated from stools of untreated 3xTgAD mice (M-FMT) or e2-FMT were transplanted in 15-month-old 3xTgAD mice. FMT was done alone or in combination with antibiotic and proton-pump inhibitor following the Microbiota Transfer Therapy protocol (MTT). The effect of donor (M or e2) and transplantation protocol (FMT or MTT) on hippocampal amyloid, tau pathology and neuroinflammation were assessed at the end of the treatment.

Results: e2-FMT reduced amyloid, and tau pathology as well as increased neuroinflammation as compared with M-FMT. MTT was associated with reduced number of Aβ40+ plaques and tau pathology. Low levels of amyloid were associated with high levels of pro-inflammatory molecules in e2-FMT mice. These associations were partially attenuated by MTT.

Conclusion: Bacteria from a human APOEe2 donor reduced AD pathology and increased neuroinflammation in mice suggesting that the gut microbiota may be a mediator of the protective effect of APOEe2.

Aim: Post-stroke-delirium has been linked to worse outcome in patients with acute cerebrovascular disease; identification of individuals at risk may prevent delirium and thereby improve outcome. We investigate prognosis and factors associated with post-stroke-delirium in patients with large vessel occlusion (LVO) ischemic stroke treated by mechanical thrombectomy (MT).

Methods: 747 patients (53.4% female) prospectively enrolled in the Gutenberg-Stroke-Study from May 2018-November 2022 were analyzed with regard to diagnosis of delirium. Group comparison of patient-, stroke- and treatment characteristics as well as computed tomography(CT)-imaging based parameters of cerebral atrophy (global cortical atrophy [GCA], posterior atrophy [Koedam], medial temporal lobe atrophy [MTA] scores) and white matter lesions (Fazekas score) was conducted. Independent predictors of delirium and the association of delirium with functional outcome at 90-day follow-up was investigated by multiple logistic regression analyses.

Results: We report 8.2% of patients (61/747) developing delirium following MT of LVO. Independent predictors were older age (aOR[95%CI] per year: 1.034[1.005-1.065], p = 0.023), male sex (aOR[95%CI]: 2.173[1.182-3.994], p = 0.012), general anesthesia during MT (aOR[95%CI]: 2.455[1.385-4.352], p = 0.002), infectious complications (aOR[95%CI]: 1.845[1.031-3.305], p = 0.039), "other determined" etiology of stroke (aOR[95%CI]: 2.424[1.100-5.345], p = 0.028), and a MTA score exceeding age-specific cut-offs (aOR[95%CI]: 2.126[1.065-4.244], p = 0.033). Delirium was independently associated with worse functional outcome (aOR[95%CI]: 2.902[1.005-8.383], p = 0.049) at 90-day follow-up.

Conclusion: Delirium is independently associated with worse functional outcome after MT of LVO, stressing the importance of screening and preventive measures. Besides conventional risk factors, pathological MTA scores and use of general anesthesia during MT may be easy-to-apply criteria to identify individuals at risk of delirium and implement prevention strategies.

Background: Abnormal interhemispheric functional connectivity is frequently reported in Parkinson's disease (PD), but its structural basis remains unclear. This study aimed to investigate changes in interhemispheric functional, structural, and callosal connectivity, as well as their interrelationships, in PD patients.

Methods: The study included 57 PD patients and 50 healthy controls (HCs). Interhemispheric functional connectivity was evaluated using voxel mirrored homotopic connectivity (VMHC) derived from resting-state functional MRI, while structural connectivity was measured through homotopic cortical thickness covariance from T1-weighted MRI. The corpus callosum (CC), connecting bilateral regions with VMHC differences, was assessed using fractional anisotropy (FA) from diffusion MRI. Pearson's correlation was used to evaluate the interrelationships among imaging data and their clinical relevance.

Results: Compared to HCs, PD patients showed reduced VMHC and interhemispheric structural connectivity in similar brain regions, displaying a positive correlation trend between these measures. The affected regions encompassed the bilateral sensorimotor cortices (precentral gyrus, postcentral gyrus, and paracentral lobule) and posterior cortical areas, including the superior parietal lobule, supramarginal gyrus, precuneus, middle occipital gyrus, fusiform gyrus, as well as the superior and middle temporal gyri. FA in the CC, connecting regions with reduced VMHC, was also lower in PD patients. Additionally, interhemispheric structural, functional, and callosal connectivity reductions were, respectively, related to cognitive impairment, motor dysfunctions, and disease duration in PD.

Conclusion: The study identified convergent reductions in interhemispheric functional, structural and callosal connectivity in PD patients, emphasizing the strong link between structural and functional brain abnormalities. Our findings may provide new insights into the pathophysiology of PD.

Introduction: Alzheimer's disease (AD) and glioblastoma (GBM) are severe neurological disorders that pose significant global healthcare challenges. Despite extensive research, the molecular mechanisms, particularly those involving mitochondrial dysfunction, remain poorly understood. A major limitation in current studies is the lack of cell-specific markers that effectively represent mitochondrial dynamics in AD and GBM.

Methods: In this study, we analyzed single-cell transcriptomic data using 10 machine learning algorithms to identify mitochondria-associated cell-specific markers. We validated these markers through the integration of gene expression and methylation data across diverse cell types. Our dataset comprised single-nucleus RNA sequencing (snRNA-seq) from AD patients, single-cell RNA sequencing (scRNA-seq) from GBM patients, and additional DNA methylation and transcriptomic data from the ROSMAP, ADNI, TCGA, and CGGA cohorts.

Results: Our analysis identified four significant cross-disease mitochondrial markers: EFHD1, SASH1, FAM110B, and SLC25A18. These markers showed both shared and unique expression profiles in AD and GBM, suggesting a common mitochondrial mechanism contributing to both diseases. Additionally, oligodendrocytes and their interactions with astrocytes were implicated in disease progression, particularly through the APP signaling pathway. Key hub genes, such as HS6ST3 and TUBB2B, were identified across different cellular subpopulations, highlighting a cell-specific co-expression network linked to mitochondrial function.

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impairs memory, cognitive function, and the ability to perform daily tasks. The pathological features of AD include β-amyloid plaques, neurofibrillary tangles, and neuronal loss. Current AD treatments target pathological changes but often fail to noticeably slow disease progression and can cause severe complications, limiting their effectiveness. In addition to therapies targeting the core pathology of AD, a more comprehensive approach may be needed for its treatment. In recent years, non-pharmacological treatments such as physical therapy, exercise therapy, cell therapy, and nanoparticles have shown great potential in mitigating disease progression and alleviating clinical symptoms. This article reviews recent advances in non-pharmacological treatment approaches for AD, highlighting their contributions to AD management and facilitating the exploration of novel therapeutic strategies.

Introduction: Evidence suggests that oxidative stress plays a critical role in the pathogenesis and progression of Alzheimer's disease (AD). Consequently, antioxidants may mitigate neurotoxicity induced by beta-amyloid (Aβ) and potentially reduce cell death. Previous research has demonstrated that olanzapine (OLZ) possesses antioxidant and neuroprotective properties. In this study, we investigated the protective and therapeutic effects of OLZ on an animal model of AD induced by Aβ using behavioral assessments.

Methods: Rats were randomly assigned to one of five groups (n = 10 rats per group): a control group, a sham group that received an intracerebrovascular (ICV) injection of phosphate-buffered saline (the solvent for Aβ), an AD group that received an ICV injection of Aβ, an OLZ group that received OLZ via gavage for two months, and an AD + OLZ group that received OLZ for one month before and one month after AD induction.

Results: We used the Elevated Plus Maze (EPM), Novel Object Recognition Test (NORT), Barnes Maze (BM), Passive Avoidance Test (PAT), and Morris Water Maze (MWM) to assess behavioral performance in the experimental rats. Aβ administration impaired cognition and increased anxiety-like behavior. Treatment with OLZ improved cognitive decline and reduced anxiety-like behavior in Aβ-infused rats.

Conclusion: Our findings suggest that OLZ can restore cognitive performance and alleviate anxiety-like behavior following Aβ injection. Thus, OLZ may have both preventive and therapeutic potential for AD and could be considered a viable pharmacological option.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), which is highly expressed in the central nervous system, is known to be involved in the regulation of mitochondrial biosynthesis, metabolic regulation, neuroinflammation, autophagy, and oxidative stress. This knowledge indicates a potential role of PGC-1α in a wide range of functions associated with neurological diseases. There is emerging evidence indicating a protective role of PGC-1α in the pathogenesis of several neurological diseases. As such, a deeper and broader understanding of PGC-1α and its role in neurological diseases is urgently needed. The present review provides a relatively complete overview of the current knowledge on PGC-1α, including its functions in different types of neurons, basic structural characteristics, and its interacting transcription factors. Furthermore, we present the role of PGC-1α in the pathogenesis of various neurological diseases, such as intracerebral hemorrhage, ischemic stroke, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and other PolyQ diseases. Importantly, we discuss some compounds or drug-targeting strategies that have been studied to ameliorate the pathology of these neurological diseases and introduce the possible mechanistic pathways. Based on the available studies, we propose that targeting PGC-1α could serve as a promising novel therapeutic strategy for one or more neurological diseases.