Frontiers in Aging Neuroscience最新文献

Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions have been confirmed in the cases of ALS with SOD1 mutations. However, the role of the OPTN gene in ALS caused by SOD1 mutations is ambiguous.

Methods: The murine Optn lentivirus and empty vector lentivirus were injected into SOD1 ^G93A mice after discovering variations in Optn expression over time. The phenotype onset date, life span, locomotor activity, and pathological changes in the spinal cord were determined and recorded subsequently. In addition, the influences on cellular apoptosis, mitochondrial dynamics, mitophagy, and neuroinflammation were further investigated.

Results: Optn expression was increased in the spinal cord of SOD1 ^G93A mice at the pre-symptomatic phase, but decreased after disease onset. Optn overexpression led to a 9.7% delay in the onset of disease and improved motor performance in SOD1 ^G93A mice. Optn overexpression also ameliorated the MNs loss by 46.8%. Moreover, all these ameliorating effects induced by Optn overexpression might be due to the inhibition of cellular apoptosis, improvement of mitochondrial quality, regulation of mitochondrial dynamics, promotion of mitophagy, and anti-inflammatory properties.

Conclusion: Our data demonstrate that Optn overexpression protects MNs, inhibites cellular apoptosis, improves mitochondrial quality and regulates neuroinflamation in SOD1 ^G93A mice at the pre-symptomatic stage.

Purpose: This study investigated the disparities in brain activation patterns during the Stroop task among individuals with mild cognitive impairment (MCI) and those without any cognitive impairments (healthy controls, HCs) using functional near-infrared spectroscopy (fNIRS).

Methods: We analyzed the cortical activation patterns of 73 patients with MCI and 63 HC individuals as they completed the Stroop task, employing fNIRS. The regions of interest (ROIs) included the dorsal prefrontal cortex (dPFC), ventrolateral prefrontal cortex (VLPFC), and parietal lobe (PL). The Stroop task is divided into early stage (0-15 s) and late stage (15-30 s). We also measured participants' behavior during the Stroop task, analyzed variations in cortical activation intensity at different experiment stages, and performed correlation analysis between Montreal Cognitive Assessment (MoCA) scores, Stroop performance, and oxygenation levels.

Results: Our analysis revealed that individuals with MCI and HC demonstrated elevated cortical activation in the dPFC, VLPFC, and PL areas while performing the Stroop task (q < 0.05, FDR-corrected). The MCI group displayed longer response latencies compared to the HC group while demonstrating comparable accuracy performance across both congruent and incongruent Stroop trials. The MCI group showed compensatory activation in the VLPFC, and PL regions compared to the HC group during the late stage of the Stroop task (q < 0.05, FDR-corrected). Correlational analysis revealed a negative association between MoCA scores and oxygenation levels in the dPFC, VLPFC, and PL regions during the late stage of the Stroop task (p < 0.05). However, no correlation was found with behavioral performance.

Conclusion: Mild cognitive impairment patients demonstrated effective compensation for their cognitive impairments at a partial behavioral level by engaging compensatory activation in the prefrontal, and parietal regions while performing the Stroop task.

Background: This study aimed to explore the association between a new inflammatory marker, systemic immune-inflammation index (SII), and the risk of Parkinson's disease (PD) in adult population.

Methods: A cross-sectional design was used, participants were recruited from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020. Three logistic regression models were used to explore the association between SII and the risk of PD, and subgroup analysis and sensitivity analysis were used. In addition, the restricted cubic spline (RCS) was used to explore the dose-response relationship between SII and PD. Receiver operating characteristic (ROC) curves was used to explore the diagnostic value of SII for PD.

Results: A total of 54,027 adults (mean age 35 years) were included in this study. The results of logistic regression showed that after adjusted for all covariates, compared with the Q1 group (lowest quartile in SII), the risk of PD in the Q3 group (OR = 1.82, 95%CI = 1.20-2.82, p < 0.001) and the Q4 group increased (OR = 2.49, 95%CI = 1.69-3.77, p < 0.001), with p-trend < 0.001. After excluding individuals with any missing values, sensitivity analysis also found a positive association between SII and PD. Subgroup analysis showed that this association was more significant in women, younger than 60 years old, non-smokers, alcohol drinkers, non-obese, and without a history of stroke, diabetes, or coronary heart disease. In addition, there was a positive dose-response relationship between SII and PD, and SII had an acceptable diagnostic value for PD (AUC = 0.72).

Conclusion: SII is positively correlated with the prevalence of PD in the adult population, and SII can help differentiate between PD and non-PD cases.

Background: Recent studies have linked disrupted cerebral hemodynamics, including pulsatility index (PI) and wall shear stress (WSS), with neuroimaging features of cerebral small vessel disease (CSVD). Cerebral neurovascular coupling (NVC) dysfunction is an important pathophysiological mechanism of CSVD. However, evidence linking the features of carotid artery hemodynamics to cerebral NVC is still lacking.

Objective: This study is aimed to explore the impact of PI and WSS on NVC and cognitive performance in CSVD patients using neuroimaging.

Methods: This study included 52 CSVD patients and 41 healthy controls. Carotid artery PI and WSS were measured using 4D flow magnetic resonance imaging (MRI). NVC was assessed through voxel-wise correlations between cerebral blood flow and the amplitude of low-frequency fluctuations. Multiple linear regression was used to investigate correlations between them.

Results: CSVD patients showed elevated PI in the C2 and C4 segments of the internal carotid artery and reduced WSS in the common carotid artery compared to controls. NVC measurements were significantly diminished in CSVD patients. Multiple linear regression analysis indicated significant correlations between reduced WSS and impaired NVC as well as between reduced PI and impaired NVC, but not between PI, WSS, and cognitive scores.

Conclusion: Reduced WSS and PI in CSVD patients are associated with impaired NVC. These findings provide insights into the mechanisms underlying CSVD and suggest that hemodynamic abnormalities may serve as indicators of neurovascular dysfunction in early-stage CSVD.

[This corrects the article DOI: 10.3389/fnagi.2024.1379011.].

In this review, we explore the mechanisms of the blood-cerebrospinal fluid (CSF) barrier and CSF transport. We briefly review the mathematical framework for CSF transport as described by a set of well-studied partial differential equations. Moreover, we describe the major contributors of CSF flow through both diffusive and convective forces beginning at the molecular level and extending into macroscopic clinical observations. In addition, we review neurosurgical perspectives in understanding CSF outflow pathways. Finally, we discuss the implications of flow dysregulation in the context of neurodegenerative diseases and discuss the rising role of perivascular drainage pathways including glymphatics.

Objective: To analyze the literature on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treating dysarthria in patients with Parkinson's disease (PD) and provide a reference for targeted clinical treatment of dysarthria in PD patients.

Methods: A systematic search was conducted in English and Chinese databases, including Embase, Cochrane, Medline, PubMed, CNKI, Wanfang, Chinese Biomedical Literature Database, and VIP Database, for relevant literature on rTMS treatment for dysarthria in PD patients. The search timeframe was from the inception of each database to October 2023. Literature was screened according to inclusion and exclusion criteria. Two researchers extracted information on study subjects, age, intervention methods, intervention duration, intervention frequency, evaluation indicators, and intervention results from the included literature. The modified Jadad scale was used to evaluate the quality of the literature.

Results: A total of seven studies were included, mainly focusing on the frequency, duration, and stimulation site of rTMS for dysarthria in PD patients. Six studies indicated that rTMS treatment improved dysarthria in PD patients.

Conclusion: Repetitive transcranial magnetic stimulation has a positive effect on improving dysarthria in PD patients, but further research is needed to determine its efficacy.

Background: Insulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.

Methods: This longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.

Results: Higher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000-0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002-0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.

Conclusion: Higher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.

Background: The aging population imposes significant economic and societal challenges, underscoring the need for early detection of individuals at risk of cognitive decline prior to the onset of clinical symptoms. This study explores the association between gamma-band Auditory Steady-State Responses (ASSRs) and subclinical cognitive decline using longitudinal data from healthy volunteers in the Metropolit Birth Cohort (MBC).

Methods: Longitudinal recordings of cognitive test results and ASSRs at 40 Hz stimulation were analyzed. Generalized Linear Models (GLMs) were employed to determine the association between ASSR characteristics and cognitive performance with an emphasis on Executive Function (EF) at ages 61-68. Additionally, Vision Transformers (ViTs) were trained to distinguish between individuals with declining and stable cognitive performance.

Results: Subjects with declining cognitive performance through midlife showed a larger area of entrainment and delayed neural assembly of ASSRs compared to those with stable cognitive performance. These neurophysiological changes were correlated with poorer EF, as measured by the Stockings of Cambridge (SOC) task. The ViTs trained and cross-validated on time-frequency-transformed Electroencephalograms (EEGs) achieved an average cross-subject accuracy of 51.8% in identifying cognitive decline.

Conclusion: Gamma-band ASSR characteristics are linked to early cognitive decline in middle-aged individuals, offering potential as biomarkers. However, the limited predictive accuracy of ML models emphasizes the need for further refinement to enhance their clinical applicability.