Frontiers in Aging Neuroscience最新文献

Background: The insula is a critical node of the salience network responsible for initiating network switching, and its dysfunctional connections are linked to the mechanisms of mild cognitive impairment (MCI). This study aimed to explore the changes in functional connectivity (FC) of insular subregions in MCI patients with varying levels of cerebrospinal fluid (CSF) pathological proteins, and to investigate the impact of these proteins on the brain network alterations in MCI.

Methods: Based on CSF Amyloid-beta (Aβ, A) and phosphorylated tau protein (p-tau, T), MCI patients were classified into 54 A-T-, 28 A+T-, and 52 A+T+ groups. Seed-based FC analysis was employed to compare the FC differences of insular subregions across the three groups. Correlation analysis was further conducted to explore the relationship between altered FC and cognitive function. Finally, ROC curve analysis was used to assess the diagnostic value of altered FC of insular subregion in distinguishing between the groups.

Results: In the left ventral anterior insula, left dorsal anterior insula, and bilateral posterior insular subnetworks, both the A+T- and A+T+ groups showed increased FC compared to the A-T- group, with the A+T+ group showing further increased FC compared to the A+T- group. Additionally, FC of the left cerebellar posterior lobe was negatively correlated with RAVLT-learning, and FC of the left middle frontal gyrus was negatively correlated with p-tau levels. Finally, logistic regression analysis demonstrated that multivariable analysis had high sensitivity and specificity in distinguishing between the groups.

Conclusion: This study showed that MCI patients with abnormal CSF pathological protein levels exhibit compensatory increases in FC of insular subregions, which in turn affect cognitive function. Our findings contributed to a better understanding of the pathophysiology and underlying neural mechanisms of MCI.

Objective: Serum neurofilament light chain (sNfL) is one of the most sensitive diagnostic biomarkers for a variety of neurodegenerative pathologies. Potassium, an essential electrolyte, plays a critical role in maintaining neuronal health and the proper functioning of the central nervous system (CNS). The aim of our research was to investigate the association between serum potassium level and sNfL levels.

Methods: Based on the National Health and Nutrition Examination Survey (NHANES) database, we analyzed data from the 2013 to 2014 NHANES. Serum potassium concentrations were measured via ion-selective electrode (ISE) technology. The levels of sNfL were measured using a sensitive immunoassay developed by Siemens Healthineers. Our researcher analyzed the association between potassium level in serum and sNfL in American persons using multivariate logistic regression analysis and smoothed curve fitting. The consistency of these results was examined in various population subgroups.

Results: A total of 1,670 participants were involved in our research, including 872 women (50.5%) and 798 men (49.5%). The median serum potassium concentration was 4.0 mmol/L and the median sNfL was 12.3 pg/ml. After adjusting for potential confounders in the full model, individuals with higher serum potassium concentrations had higher sNfL levels (Q3 vs. Q1, β = 2.86, 95% CI: 0.33-5.39, P = 0.027). There was a non-linear positive dose-response association between higher serum potassium concentrations and sNfL levels (P for non-linearity = 0.028). Based on the results of stratified analysis, the relationship was stronger in the low- and middle-income group, non-drinking and non-physical activity participants, and participants with hypertension and diabetes.

Interpretation: In the cohort of American adults, a greater serum potassium concentration was linked to a higher sNfL. However, causality still needs to be further verified.

Introduction: The association between hyperlipidemia and its potential role as a risk factor for postoperative delirium (POD) remains unclear.

Methods: We systematically searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify studies meeting the inclusion criteria. Outcomes of interest included comparisons of blood lipid levels between POD and non-POD (NPOD) patients, the association between hyperlipidemia and POD risk, and the predictive value of hyperlipidemia for POD.

Results: A total of nine studies involving 4,686 patients were included in the meta-analysis. Pooled analysis revealed that hyperlipidemia was significantly associated with an increased risk of POD (OR = 1.47; 95% CI 1.13-1.91; P = 0.004;) compared to patients without hyperlipidemia. Patients with POD exhibited significantly higher levels of total cholesterol (TC) (weighted mean difference [WMD] = 0.31; 95% CI 0.03-0.59; P = 0.030), triglycerides (TG) (WMD = 0.37; 95% CI 0.03-0.71; P = 0.033), and low-density lipoprotein cholesterol (LDL-C) (WMD = 0.09; 95% CI 0.01-0.17; P = 0.023) compared to NPOD patients. In contrast, high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in POD patients (WMD = -0.07; 95% CI -0.12 to -0.01; P = 0.026). Insufficient evidence was available to summarize the area under the curve (AUC) results.

Conclusions: Blood lipid levels were significantly elevated in POD patients compared to NPOD patients. Hyperlipidemia was significantly associated with an increased risk of POD, highlighting its potential role as a risk factor.

Objectives: To evaluate the effect of preoperative continuation vs. discontinuation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on early cognitive function in elderly patients undergoing noncardiac surgery.

Methods: This prospective randomized controlled study was performed at the Affiliated Hospital of Xuzhou Medical University. Elderly patients aged 65 years or older, scheduled for elective noncardiac surgery under general anesthesia, and receiving long-term ACEI/ARBs therapy were randomly assigned to either continue or discontinue ACEI/ARBs therapy on the morning of surgery. The primary outcome was postoperative early cognitive function, assessed via neuropsychological tests including Auditory Verbal Learning Test-Huashan (AVLT-H), Clock Drawing Test (CDT), Number Connection Test (NCT), and Digit Span Test (DST) preoperatively and on postoperative day 1 (POD1). Secondary outcomes included intraoperative hypotension, use of phenylephrine, intraoperative fluid administration, incidence of hypertension, and length of hospital stay.

Results: The NCT scores in the discontinued use of ACEI/ARBs group showed a significant decline on POD1 compared to baseline (p = 0.038). Both groups exhibited an increase in immediate recall scores from preoperative to POD1 (p = 0.003 and p = 0.002, respectively). The continued use of ACEI/ARBs group showed an increase in short-delayed recall (p = 0.007). However, there were no significant differences between the two groups (p > 0.05). The discontinued ACEI/ARB group had fewer episodes of intraoperative hypotension (p = 0.037) and lower requirements for phenylephrine (p = 0.016), despite a higher incidence of preoperative hypertension (p = 0.012). The continued use group received a larger volume of crystalloid fluids during surgery (p = 0.020). No significant differences were observed between the groups in the volume of colloid fluids administered (p > 0.05). There were no significant differences in postoperative hypertension or length of hospital stay between the groups (p > 0.05).

Conclusion: Preoperative continuation or discontinuation of ACEI/ARBs did not significantly affect early postoperative cognitive function in elderly patients.

Introduction: As the proportion of older people has surged in the past 100 years, healthy aging has emerged as a crucial topic in neuroscience research. This study aimed to investigate the spectral power of EEG frequency bands during resting-state in older people with high and low cognitive reserve (CR).

Methods: To do so, 74 healthy older people (55-74 years old) were recruited and divided into two groups based on their level of CR: high CR (n = 41; 21 men and 20 women) and low CR (n = 33; 15 men and 18 women). Both groups participated in a cognitive assessment and 3 min of EEG recording under resting-state conditions with eyes open (EO) and eyes closed (EC). EEG power was analyzed across four frequency bands: delta (0.1- < 4 Hz), theta (4- < 8 Hz), alpha1 (8-10 Hz), alpha2 (10-12), and beta (14-30 Hz), focusing on five cortical regions of interest.

Results: Neuropsychological tests did not reveal significant differences between the two groups on most of the cognitive measures. However, the EEG analysis showed that individuals with high CR exhibited lower spectral power in the theta and delta frequency bands across different brain regions, compared to those with low CR.

Discussion: These findings suggest that individuals with high CR tend to function more efficiently, relying on fewer neural resources to sustain cognitive performance. In contrast, those with low CR may engage compensatory neural mechanisms, as indicated by increased spectral power while resting, conceivably reflecting the brain's effort to preserve cognitive function.

Objectives: Early-life inflammatory events like infections and injuries may predispose the brain to Alzheimer's disease (AD) by disrupting neurodevelopment and raising vulnerability. The association between early neuroinflammation and subsequent neurodegeneration leading to dementia remains unclear. We hypothesize that omega-3 (n-3) fatty acids (FA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), positively regulate neuro-immune cells, preserving their cell membrane structure and metabolic homeostasis. Our study examined whether strategic delivery of n-3 FA via injectable n-3 triglycerides (TG) can influence microglial lipid metabolism to prevent or delay AD progression.

Methods and results: We characterized n-3 treatment effects on modulating lipid and metabolic homeostasis in microglia during the critical window of brain development. Our preliminary studies on determining the effects of early n-3 treatment on brain cell homeostasis indicate that perinatal bolus n-3 TG injections suppressed activation of gliosis-associated markers in young mice predisposed to AD (5xFAD) and yielded sustained regulatory effects on the expression of inflammatory molecules, such as interleukin-6 (Il6) and tumor necrosis factor-alpha (Tnfα), in adult brains. A significant increase in high-frequency ultrasonic vocalizations (USV) was observed in P6 5xFAD mice that received perinatal n-3 compared to vehicle control, implicating enhanced active communication patterns. Improvement in behavior deficits was observed in n-3-treated adult AD mice. Perinatal n-3 TG treatment modified brain lipid composition in young offspring, increasing key membrane lipid species, such as phospholipids (PL) and lysophospholipids (lysoPL). Pro-inflammatory sphingolipids associated with neurodegeneration, including lactosylceramide, were significantly lower in mice treated with n-3 than those in saline-treated AD mice.

Conclusion: Our study establishes a proof of principle for targeting brain immune cell metabolism with injectable n-3 TG to mitigate neuroinflammation in AD pathogenesis, paving the way for future research into early treatments for related central nervous system (CNS) disorders.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and neuronal degeneration. Emerging evidence implicates necroptosis in AD pathogenesis, driven by the RIPK1-RIPK3-MLKL pathway, which promotes neuronal damage, inflammation, and disease progression. Exercise, as a non-pharmacological intervention, can modulate key inflammatory mediators such as TNF-α, HMGB1, and IL-1β, thereby inhibiting necroptotic signaling. Additionally, exercise enhances O-GlcNAc glycosylation, preventing Tau hyperphosphorylation and stabilizing neuronal integrity. This review explores how exercise mitigates necroptosis and neuroinflammation, offering novel therapeutic perspectives for AD prevention and management.

Background and aims: As the country with the largest and fastest-aging older population worldwide, China has hosted an increasing number of regional investigations into disability among older adults. However, the prevalence of disabilities related to physical function and cognition in southern China remains unknown. This study aimed to assess the prevalence of and associated factors for cognitive and physical function impairment in individuals aged 60 years and older.

Methods: For this population-based cross-sectional study, a total of 5,603 participants were recruited between June 2021 and December 2022 using a multistage, stratified, cluster sampling procedure. Instruments, including a general questionnaire, basic and instrumental activities of daily living, the Chinese version of the Mini-Mental State Examination (MMSE), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7), were used to collect data through a WeChat mini program. Binary and multivariate logistic regression analyses were applied to explore the influencing factors.

Results: The prevalence of physical function and cognitive impairment among older adults was 37.3 and 31.0%, respectively. Multivariate regression analyses revealed that age, family income, education level, place of residence, medication type, annual physical examinations, weekly social activities, support from family or friends, hearing disorders, walking disorders, and depression were all associated with both physical function and cognitive impairment. Moreover, an increased risk of physical function impairment correlated with BMI, region, income source, smoking, and weekly exercise, while cognitive impairment was associated with the number of children, insurance type, coronary heart disease, and anxiety. Physical function (OR: 1.79, 95% CI: 1.49-2.16) and cognitive impairment (OR: 1.83, 95% CI: 1.51-2.21) were mutually influential in our study.

Conclusion: This study showed a high prevalence of various factors related to physical function and cognitive impairment. The results revealed that comprehensive and systematic prevention and control programs for disabilities should be developed to improve the quality of life for older adults.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, best known for its motor symptoms such as resting tremor, muscle rigidity, and bradykinesia. However, autonomic dysfunction is an important non-motor aspect that often brings considerable discomfort and distress to both patients and their families. In this review, we summarize recent advances in understanding the pathophysiological mechanisms of autonomic dysfunction and explore its relationship with other clinical features. Our aim is to discover novel potential diagnostic and therapeutic strategies, alleviate patient suffering, and pave the way for future clinical and basic research.