BACKGROUND: In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers.
METHODS: Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N = 29, F/M = 17/12) and Non-Hispanic White (N = 47, F/M = 27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aβ)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes.
RESULTS: Results revealed a significant race × Aβ42 interaction in Black Americans: lower Aβ42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals.
CONCLUSIONS: Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer\'s disease risk pathology during middle age, particularly in Black Americans.
CONCLUSIONS: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aβ42 in Black Americans. Precuneus may be a hub for early Alzheimer\'s disease pathology changes detected by functional connectivity.

While chronic smoking triggers cardiovascular disease, controversy remains regarding its effects on the brain and cognition. We investigated the effects of long-term cigarette smoke (CS) exposure (CSE) on cerebrovascular function, neuronal injury, and cognition in a novel mouse exposure model. Longitudinal studies were performed in CS or air-exposed mice, 2 hours/day, for up to 60 weeks. Hypertension and carotid vascular endothelial dysfunction (VED) occurred by 16 weeks of CSE, followed by reduced carotid artery blood flow, with oxidative stress detected in the carotid artery, and subsequently in the brain of CS-exposed mice with generation of reactive oxygen species (ROS) and secondary protein and DNA oxidation, microglial activation and astrocytosis. Brain small vessels exhibited decreased levels of endothelial NO synthase (eNOS), enlarged perivascular spaces with blood brain barrier (BBB) leak and decreased levels of tight-junction proteins. In the brain, amyloid-β deposition and phosphorylated-tau were detected with increases out to 60 weeks, at which time mice exhibited impaired spatial learning and memory. Thus, long-term CSE initiates a cascade of ROS generation and oxidative damage, eNOS dysfunction with cerebral hypoperfusion, as well as cerebrovascular and BBB damage with intracerebral inflammation, and neuronal degeneration, followed by the onset of impaired cognition and memory.

UNASSIGNED: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity.
UNASSIGNED: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed.
UNASSIGNED: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort.
UNASSIGNED: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.

暂无摘要。

BACKGROUND: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM).
METHODS: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined.
RESULTS: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77), and stroke (OR 1.47, 95%CI 1.04-2.09).
CONCLUSIONS: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Background: Depression is the most common mental illness worldwide and generates an enormous health and economic burden. Furthermore, it is known to be associated with an elevated risk of arteriosclerotic cardiovascular diseases (ASCVD), particularly stroke. However, it is not a factor reflected in many ASCVD risk models, including SCORE2. Thus, we analysed the relationship between depression, ASCVD and SCORE2 in our cohort. Methods: We analysed 9350 subjects from the Paracelsus 10,000 cohort, who underwent both a carotid artery ultrasound and completed a Beck Depression Inventory (BDI) screening. Patients were categorised binomially based on the BDI score. Atherosclerotic carotid plaque or absence was dichotomised for logistic regression modelling. Odds ratios and adjusted relative risks were calculated using Stata. Results: Subjects with an elevated BDI (≥14) had higher odds for carotid plaques compared to subjects with normal BDI, especially after adjusting for classical risk factors included in SCORE2 (1.21; 95%CI 1.03-1.43, p = 0.023). The adjusted relative risk for plaques was also increased (1.09; 95%CI 1.01-1.18, p = 0.021). Subgroup analysis showed an increased odds of plaques with increases in depressive symptoms, particularly in women and patients ≤55 yrs. Conclusions: In our cohort, the BDI score is associated with subclinical atherosclerosis beyond classical risk factors. Thus, depression might be an independent risk factor which may improve risk stratification if considered in ASCVD risk prediction models, such as SCORE2. Furthermore, reminding clinicians to take mental health into consideration to identify individuals at increased atherosclerosis risk may provide added opportunities to address measures which can reduce the risk of ASCVD.

UNASSIGNED: This study aimed to investigate the prevalence of carotid atherosclerosis (CAS), especially among seniors, and develop a precise risk assessment tool to facilitate screening and early intervention for high-risk individuals.
UNASSIGNED: A comprehensive approach was employed, integrating traditional epidemiological methods with advanced machine learning techniques, including support vector machines, XGBoost, decision trees, random forests, and logistic regression.
UNASSIGNED: Among 1,515 participants, CAS prevalence reached 57.4%, concentrated within older individuals. Positive correlations were identified with age, systolic blood pressure, a history of hypertension, male gender, and total cholesterol. High-density lipoprotein (HDL) emerged as a protective factor against CAS, with total cholesterol and HDL levels proving significant predictors.
UNASSIGNED: This research illuminates the risk factors linked to CAS and introduces a validated risk scoring tool, highlighted by the logistic classifier\'s consistent performance during training and testing. This tool shows potential for pinpointing high-risk individuals in community health programs, streamlining screening and intervention by clinical physicians. By stressing the significance of managing cholesterol levels, especially HDL, our findings provide actionable insights for CAS prevention. Nonetheless, rigorous validation is paramount to guarantee its practicality and efficacy in real-world scenarios.

暂无摘要。

White matter hyperintensity (WMH) shape is associated with long-term dementia risk in community-dwelling older adults, however, the underlying structural correlates of this association are unknown. We therefore aimed to investigate the association between baseline WMH shape and cerebrovascular disease progression over time in community-dwelling older adults. The association of WMH shape and cerebrovascular disease markers was investigated using linear and logistic regression models in the Age, Gene/Environment Susceptibility-Reykjavik (AGES) study (n = 2297; average time to follow-up: 5.2 years). A more irregular shape of periventricular/confluent WMH at baseline was associated with a larger increase in WMH volume, and with occurrence of new subcortical infarcts, new microbleeds, new enlarged perivascular spaces, and new cerebellar infarcts at the 5.2-year follow-up (all p < 0.05). Furthermore, less elongated and more irregularly shaped deep WMHs were associated with a larger increase in WMH volume, and new cortical infarcts at follow-up (p < 0.05). A less elongated shape of deep WMH was associated with new microbleeds at follow-up (p < 0.05). Our findings show that WMH shape may be indicative of the type of cerebrovascular disease marker progression. This underlines the significance of WMH shape to aid in the assessment of cerebrovascular disease progression.

UNASSIGNED: Cardioembolic stroke (CES) appears to be a rare cause of stroke (4%-9%) in people living with HIV (PLWH) in sub-Saharan Africa (SSA). However, due to limited access to diagnostic resources, this may be an underestimate. It is also unclear which cardiac pathologies are the major contributors to CES in this region. We sought to determine the prevalence and aetiology of CES in PLWH and to determine whether there are any differences compared with HIV negative stroke patients.
UNASSIGNED: This cross-sectional study recruited PLWH with new-onset stroke at a quaternary-level hospital in Johannesburg, South Africa, from 2014 to 2017, and compared them to age-matched and sex-matched HIV negative stroke patients. Comprehensive investigations were performed to determine the underlying stroke aetiology, including electrocardiography, echocardiography, CT angiography and cerebrospinal fluid examination.
UNASSIGNED: 85 PLWH with ischaemic stroke were recruited and compared with 109 HIV negative controls. CES was identified in 17/85 (20.0%) of PLWH. These patients had more severe strokes than PLWH with non-CES (National Institutes of Health Stroke Scale score 14.9±6.7 vs 11.7±5.4, p=0.04). Cardiomyopathy was the predominant cardiac pathology in PLWH (76.4% vs 45.5% in HIV negative, p=0.04) while valvulopathy was more common in HIV negative patients (42.4% vs 11.8% in PLWH, p=0.03). Arrhythmia (n=1) and ischaemic heart disease (n=1) were uncommon in PLWH.
UNASSIGNED: CES is underdiagnosed in SSA and is more severe than non-CES. The identification of cardiomyopathy as the predominant underlying cardiac pathology may assist to target resources towards its detection using accessible cost-effective biomarkers.