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Background Neurofilament Light (NfL) is a biomarker for early neurodegeneration in Alzheimer’s disease (AD). This study aims to examine the association between plasma NfL and multi-modal neuroimaging features across the AD spectrum and whether NfL predicts future tau deposition. Methods The present study recruited 517 participants comprising Aβ negative cognitively normal (CN-) participants (n  =  135), Aβ positive cognitively normal (CN +) participants ( n  = 64), individuals with amnestic mild cognitive impairment (aMCI) ( n  = 212), and those diagnosed with AD dementia ( n  = 106). All the participants underwent multi-modal neuroimaging examinations. Cross-sectional and longitudinal associations between plasma NfL and multi-modal neuro-imaging features were evaluated using partial correlation analysis and linear mixed effects models. We also used linear regression analysis to investigate the association of baseline plasma NfL with future PET tau load. Mediation analysis was used to explore whether the effect of NfL on cognition was mediated by these imaging biomarkers. Results The results showed that baseline NfL levels and the rate of change were associated with Aβ deposition, brain atrophy, brain connectome, glucose metabolism, and brain perfusion in AD signature regions ( P <0.05). In both Aβ positive CN and MCI participants, baseline NfL showed a significant predictive value of elevating tau burden in the left medial orbitofrontal cortex and para-hippocampus (β = 0.336, P  = 0.032; β = 0.313, P  = 0.047). Lastly, the multi-modal neuroimaging features mediated the association between plasma NfL and cognitive performance. Conclusions The study supports the association between plasma NfL and multi-modal neuroimaging features in AD-vulnerable regions and its predictive value for future tau deposition.

Background Stress hyperglycemia is a relatively transient increase in blood glucose in response to inflammation of the body and neurohormonal disorders. It is still debated whether stress hyperglycemia ratio (SHR) in the acute phase, a new indicator of stress hyperglycemia, is related to poor prognosis in acute ischemic stroke (AIS) patients. This meta-analysis provides insight into the connection between SHR and prognosis in AIS patients. Methods We screened all potentially relevant studies using a comprehensive database search. The standardized mean difference (SMD) and 95% confidence interval (CI) were utilized to investigate the relationship between SHR in the acute phase and the prognosis of AIS. Results The pooled results revealed that AIS patients with poor prognoses had significantly higher SHR values than those with good prognoses (SMD = 0.56, 95%CI: 0.37–0.75, p <0.001). Subgroup analysis indicated that study design and differences in post-stroke treatment might be the sources of heterogeneity in this meta-analysis. Conclusions High SHR in the acute period is related to poor prognosis after AIS. SHR may be a new predictor of poor outcomes in AIS patients.

Background Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. Methods This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 10 3 /μL) / HDL cholesterol (mmol/L). Results In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [ β  = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07–1.91], and CMB (aOR = 1.51, 95% CI = 1.03–2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH ( P  < 0.001), lacunes ( P  < 0.001), and CMBs ( P  < 0.001). Conclusions High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs.

Background Sleep disorders are a prevalent non-motor symptom of Parkinson’s disease (PD), although reliable biological markers are presently lacking. Objectives To explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD. Methods The study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models. Results In baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors ( β  = 0.033; P  = 0.042) and movements of arms or legs during sleep ( β  = 0.027; P  = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep ( β  = 0.038; P  = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score ( β  = 0.002; P  = 0.011) or who were considered as probable RBD ( β  = 0.012; P  = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score ( β  = 0.001; P  = 0.012) or who were regarded to have EDS ( β  = 0.013; P  = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels. Conclusion Sleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes.

Background Little is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. Methods Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40–73 years at baseline (between 2006–2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. Results During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55–2.85) and 3.72(3.40–4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother’s history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. Conclusions Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother’s history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

Background Status epilepticus (SE) is a severe acute condition in neurocritical care with high mortality. Searching for risk factors affecting the prognosis in SE remains a significant issue. The primary study’s aim was to test the predictive values of the Clinical Frailty Scale (CFS) and the Modified 11-item Frailty Index (mFI-11), the biomarkers and basic biochemical parameters collected at ICU on the Glasgow Outcome Scale (GOS) assessed at hospital discharge (hosp), and three months later (3 M), in comatose patients with SE. The secondary aim was to focus on the association between the patient’s state at admission and the duration of mechanical ventilation, the ICU, and hospital stay. Methods In two years single-centre prospective pilot study enrolling 30 adult neurocritical care patients with SE classified as Convulsive SE, A.1 category according to the International League Against Epilepsy (ILAE) Task Force without an-/hypoxic encephalopathy, we evaluated predictive powers of CFS, mFI-11, admission Status Epilepticus Severity Score (STESS), serum protein S100, serum Troponin T and basic biochemical parameters on prognosticating GOS using univariate linear regression, logistic regression and Receiver Operating Characteristic (ROC) analysis. Results Our study included 60% males, with a mean age of 57 ± 16 years (44–68) and a mean BMI of 27 ± 5.6. We found CFS, mFI-11, STESS, and age statistically associated with GOS at hospital discharge and three months later. Among the biomarkers, serum troponin T level affected GOS hosp ( p  = 0.027). Serum C-reactive protein significance in prognosticating GOS was found by logistic regression (hosp p  = 0.008; 3 M p  = 0.004), and serum calcium by linear regression (hosp p  = 0.028; 3 M p  = 0.015). In relation to secondary outcomes, we found associations between the length of hospital stay and each of the following: age ( p  = 0.03), STESS ( p  = 0.009), and serum troponin T ( p  = 0.029) parameters. Conclusions This pilot study found promising predictive powers of two frailty scores, namely CFS and mFI-11, which were comparable to age and STESS predictors regarding the GOS at hospital discharge and three months later in ICU patients with SE. Among biomarkers and biochemical parameters, only serum troponin T level affected GOS at hospital discharge.

Background Glycated albumin (GA) is an indicator of glycemic variability over the past 2–4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). Methods We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). Results In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10–9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01–1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14–3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. Conclusions High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Background & Objectives Objective assessment of post-COVID-19 cognitive dysfunction is highly warranted. This study aimed to evaluate the cognitive dysfunction of COVID-19 survivors with cognitive complaints, both clinically and neurophysiologically, using Quantitative Electroencephalogram (QEEG). Methods This case–control study was conducted on 50 recovered subjects from COVID-19 infection with cognitive complaints and 50 age, sex, and educational-matched healthy controls. Both groups were subjected to the following neurocognitive tests: Paired associate learning Test (PALT) and Paced Auditory Serial Addition Test (PASAT). The neurophysiological assessment was also done for both groups using QEEG. Results COVID-19 survivors had significantly lower PALT scores than controls ( P  < 0.001). QEEG analysis found significantly higher levels of Theta / Beta ratio in both central and parietal areas in patients than in the controls ( P  < 0.001 for each). The interhemispheric coherence for the frontal, central, and parietal regions was also significantly lower in patients than in the control group regarding alpha and beta bands. There were statistically significant lower scores of PALT and PASAT among cases with severe COVID-19 infection ( P  =  0.011, 0.005 , respectively) and those who needed oxygen support ( P  = 0.04, 0.01, respectively). On the other hand, a statistically significantly lower mean of frontal alpha inter-hemispheric coherence among patients with severe COVID-19 infection ( P  = 0.01) and those needing mechanical ventilation support ( P  = 0.04). Conclusion Episodic memory deficit is evident in COVID-19 survivors with subjective cognitive complaints accompanied by lower inter-hemispheric coherence in frontal regions. These clinical and neurophysiological changes are associated with hypoxia and COVID-19 severity.

Background Trimethylamine-N-oxide (TMAO), an intestinal microbiota-derived choline metabolite, has been found to be associated with ischemic stroke (IS) in more and more studies. However, the causal role of TMAO on IS occurrence remains perplexing. Methods We comprehensively screened the related clinical studies on PubMed, Web of Science, and Embase. Case-control and cohort studies that reported the TMAO levels of both IS patients and healthy controls were included, and the risk of bias was assessed according to the criteria by the Centre for Evidence-Based Medicine in Oxford, UK. A meta-analysis of the retrieved publications was performed with a random-effect model to analyze the connection between TMAO levels and IS events. Besides, a Mendelian randomization (MR) analysis was performed to study the causal effect of TMAO on IS, with pooled data of TMAO and IS obtained from genome-wide association studies (GWAS). The following methods were used: MR-Egger, weighted median, inverse-variance weighted, simple mode, and weighted mode. The study has been registered in INPLASY (Registration number: INPLASY2023100027). Results Eight cohort or case-control studies covering 2444 cases and 1707 controls were identified. The pooled data indicated that the IS patients tended to have higher TMAO levels compared with the controls (mean difference: 1.97 μM; 95% confidence interval [CI]: 0.87, 3.07; P  = 0.0005), while distinctive heterogeneity ( I 2  = 96%, P  < 0.00001) was observed. Sub-group analysis revealed that the heterogeneity of the studies might be derived from the studies themselves. However, no causal effect of TMAO on IS was observed ( P  > 0.05) in the Mendelian randomization analysis of this study. Conclusion We confirmed that IS patients tend to have higher TMAO levels than healthy individuals, while our findings of MR analysis did not support the causal role of TMAO in IS occurrence. Therefore, more studies are required for a better understanding of the relationship between TMAO levels and IS onset.

Background Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular junction. The literature suggests the involvement of circulating cytokines (CK), gut microbiota (GM), and serum metabolites (SM) with MG. However, this research is limited to observational trials, and comprehensive causal relationship studies have not been conducted. Based on published datasets, this investigation employed Mendelian Randomization (MR) to analyze the known and suspected risk factors and biomarkers causal association of MG and its subtypes. Methods This research used two-sample MR and linkage disequilibrium score (LDSC) regression of multiple datasets to aggregate datasets acquired from the genome-wide association studies (GWAS) to assess the association of MG with 41-CK, 221-GM, and 486-SM. For sensitivity analysis and to validate the robustness of the acquired data, six methods were utilized, including MR-Egger regression, inverse variance weighting (IVW), weighted median, and MR-PRESSO. Results The MR method identified 20 factors significantly associated with MG, including 2 CKs, 6 GMs, and 9 SMs. Further analysis of the factors related to the two MG subtypes, early-onset MG (EOMG) and late-onset MG (LOMG), showed that EOMG had a high overlap with MG in the intestinal flora, while LOMG had a greater similarity in CKs and SMs. Furthermore, LDSC regression analysis indicated that Peptococcaceae , oxidized biliverdin, and Kynurenine had significant genetic correlations with general MG, whereas EOMG was highly correlated with Intestinibacter , while LOMG had significant genetic associations with Kynurenine and Glucose. Conclusion This research furnishes evidence for the potential causal associations of various risk factors with MG and indicates a heterogeneous relationship between CKs, GMs, and SMs with MG subtypes.