Search Results for: La carne alla griglia favorisce Alzheimer e diabete

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Stroke, Ahead of Print. As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter injury, their risk factors, and comorbidities on cognitive performance among a diverse, nondemented, stroke-free population with cognitive complaints over an extended period of observation. The Diverse VCID (Diverse Vascular Cognitive Impairment and Dementia) study is designed to fill this knowledge gap through 3 assessments of clinical, behavioral, and risk factors; neurocognitive and magnetic resonance imaging measures; fluid biomarkers of Alzheimer disease, vascular inflammation, angiogenesis, and endothelial dysfunction; and measures of genetic risk collected prospectively over a minimum of 3 years in a cohort of 2250 individuals evenly distributed among Americans of Black/African, Latino/Hispanic, and non-Hispanic White backgrounds. The goal of this study is to investigate the basic mechanisms of small vessel cerebrovascular injury, emphasizing clinically relevant assessment tools and developing a risk score that will accurately identify at-risk individuals for possible treatment or clinical therapeutic trials, particularly individuals of diverse backgrounds where vascular risk factors and disease are more prevalent.

Neurologi: ‘si apre una nuova storia per i pazienti’

I moderni dispositivi permettono di adattare la terapia insulinica alle esigenze individuali di ciascun paziente, migliorando l’efficacia del trattamento

Il Ceo della farmaceutica indiana: «l’Europa è un mercato chiave e stiamo investendo per estendere l’accesso alle cure in aree cruciali come oncologia, immunologia e diabete»

Il Ceo della farmaceutica indiana: «l’Europa è un mercato chiave e stiamo investendo per estendere l’accesso alle cure in aree cruciali come oncologia, immunologia e diabete»

Cherubini (Siedp) “evitabili in oltre 450 bimbi ogni anno”

Circulation, Volume 150, Issue Suppl_1, Page A4147625-A4147625, November 12, 2024. Background:Cardiometabolic syndrome (CMS) poses a significant public health concern. The study aimed to investigate the predictive value of age and CMS for incident Alzheimer’s disease (AD) in women aged≥50.Methods:A cohort of women aged 50-79 (n= 63,117) who participated in the Women’s Health Initiative Observational Study (WHIOS) in 1993-1998, without baseline AD and followed through to March 1, 2019, were analyzed. CMS was defined as having ≥3 of five CMS components: large waist circumference, HBP, elevated triglycerides, elevated glucose, and low HDL-cholesterol. AD was classified by physician-diagnoses of incident AD. Hazards ratios (HR) of AD risk associated with CMS by age were analyzed using Cox’s proportional hazards regression analysis. Machine learning (ML)-XGBoost and Lasso Cox models clustered individuals with low, mild, moderate, and severe risk of incident AD.Results:During a median follow-up of 20 years (range: 3.36 to 23.36 years), 8340 developed incident AD. The incident rate (95%CI) of AD was 8.6 (8.1-9.1) per 1000 person-years (PY) in women with CMS, and 7.0 (6.9-7.2) per 1000 PY in those without CMS (p

Circulation, Volume 150, Issue Suppl_1, Page A4132120-A4132120, November 12, 2024. Epidemiological studies indicate that individuals with Down syndrome (DS) have an increased risk of leukemia and neuronal diseases but a significantly reduced incidence of most solid tumors and advanced vascular dysfunction. This suggests that one or a combination of trisomy genes on human chromosome 21 (HSA21) or murine chromosome 16 (Mmu16) may be responsible for protecting against vasculopathy. Our previous research has shown that theDown syndrome critical region (Dscr)-1gene, located on HSA21 orMmu16, encodes a feedback modulator of calcineurin-NFAT signaling in endothelial cells (ECs). Null mutation or overexpression of Dscr-1 has been found to increase or prevent septic mortality, angiogenesis, liver steatosis, and susceptibility of tumor metastasizing to the lung, respectively, demonstrating its significant role in these processes.In a unique approach, we crossed DS model mice withApoE-null mice and fed them a high-fat diet (HFD) for 12 weeks to survey the effects of DS-related genes on atherosclerosis. The results were striking, with HFD-mediated increased LDL and triglyceride levels inApoE-null mice significantly reduced in the combined DS plusApoE-null mice. This innovative method allowed us to observe a remarkable (~35%) reduction in ApoE-null mediated atheroma formation in the DS model. This finding was also replicated in EC-specific DSCR-1 transgenic (DSCR-1ECTg) mice.Furthermore, to test the effect of HSA21, we have collected DS patient-derived trisomy and disomy iPS cells and executed them for the chromatin conformation capture analysis and thein vitroECs differentiation experiments. DS-derived trisomy iPS cells already changed the whole chromatin structure, typically within the X chromosome. Moreover, the trisomy iPS-derived ECs revealed less proliferation compared to the disomy. RNA-seqs indicated trisomy iPS derived ECs dramatically (21-fold) increasedDSCR-1, but some HSA21 genes, Alzheimer’s relatedAppandBace2, e.g., were inversely reduced the expression.Our comprehensive studies not only shed new light on the mechanisms of atherosclerosis in vascular pathology but also offer potential therapeutic strategies. The discovery of theDscr-1gene on the DS chromosome, which could be a powerful tool in combating lifestyle-related vascular diseases, underscores the significance of our research.

Circulation, Volume 150, Issue Suppl_1, Page A4124039-A4124039, November 12, 2024. Background:Age is the most important risk factor for coronary artery disease (CAD), independent of traditional risk factors such as hypertension, diabetes (DM), hyperlipidemia and smoking, through poorly understood mechanisms. Medin, a cleavage product of MFGE8 protein that forms the most common human amyloid, accumulates in the vasculature with age, including the coronary arteries. Although medin amyloid has been implicated in various diseases such as Alzheimer’s disease, vascular dementia and aortic aneurysms, its role in CAD remains unknown. Medin was shown to induce changes characteristic of vascular aging, such as endothelial and smooth muscle dysfunction in human donor cerebral arteries. Medin also induced proinflammatory activation of human brain microvascular endothelial cells through NFκB activation .Aims:To determine the effects of medin on pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells (HCAECs).Methods:Primary HCAECs (passages 6-8) were exposed for 20 hours to physiologic doses of recombinant medin (0.5, 1 and 5 µM) and gene expression of pro-inflammatory proteins (IL-6, IL-8, IL-1b and intercellular adhesion molecule (ICAM)-1), prothrombotic protein (plasminogen activator inhibitor (PAI)-1) and anticoagulant membrane protein thrombomodulin were quantified using rtPCR and compared. Separately, HCAECs were exposed to medin (0.5, 1 and 5 µM) with or without small molecule specific inhibitor of NFκB (RO106-9920, 10 uM) for 20 hours and protein expression of IL-6 in conditioned media was measured using ELISA.Results:Medin caused dose-dependent increases in gene expressions of pro-inflammatory cytokines IL-6, IL-8, IL-1b, ICAM-1 (Figure 1 A-D). Medin caused a dose-dependent increase in PAI-1 and a dose-dependent decrease in thrombomodulin (Fig. 1 E-F). Co-treatment with RO106-9920 prevented medin-induced increase in IL-6 protein expression (Fig. 1G).Conclusions:Medin induces pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells. The proinflammatory activation is likely NFκB-dependent. Medin is a promising potential novel mediator of CAD and vascular aging.

Circulation, Volume 150, Issue Suppl_1, Page A4144534-A4144534, November 12, 2024. Background:Anxiety, depression, and cognitive changes are common adverse outcomes after acute coronary syndromes (ACS). These challenges also predict increased risk of adverse cardiac outcomes. While it is known that females have higher rates of psychological symptoms generally, data on sex differences in onset following an acute cardiac event are scarce, especially among older adults.Goal:Our goal was to determine if sex differences exist in mental health and cognitive outcomes after acute coronary syndrome in older adults.Hypothesis:Females are more likely to have new psychological and cognitive issues within one year of ACS compared to male patients.Methods:We conducted a retrospective analysis using Texas Medicare claims data from 2017-2020. The study population consisted of those 65 and older, diagnosed with ACS (either STEMI or NSTEMI). Eligible participants had continuous enrollment in Medicare Part A and B for at least one year before and after the index event, were not part of any Health Maintenance Organization, and had no prior diagnosis of the outcomes of interest (anxiety, depression, amnesia, and dementia). Data were extracted on demographic characteristics, clinical variables, and intervention (i.e. PCI/CABG). Descriptive statistics were used to summarize the data.Results:Our study included 56,325 patients (23,911, 42.4% female), 13,078 with STEMI and 43,247 with NSTEMI. In STEMI and NSTEMI patients respectively, the prevalence of onset of the following outcomes was significantly higher among females compared to males: anxiety (14.8% vs. 9.3%; 16.2% vs. 11.3%), depression (11.5% vs. 7.9%; 14.1% vs. 9.9%), and dementia/Alzheimer’s (2.5% vs. 1.7%; 3.5% vs. 2.5%). No differences were observed in amnesia by sex. Differences by sex persisted by treatment type for anxiety and depression (Table). Additionally, rates of new diagnoses were higher across sexes for CABG compared to PCI.Conclusion:Significant sex differences exist in cognitive and mental health outcomes after ACS. Females are more likely to have worse outcomes following ACS as compared to men. Additionally, across sexes, psychological outcomes are worse following CABG as compared to PCI.

Circulation, Volume 150, Issue Suppl_1, Page A4146396-A4146396, November 12, 2024. Introduction/Background:By 2050, the U.S. will see a demographic shift where individuals over 65 outnumber those under 65. This change underscores a rising prevalence of neurodegenerative diseases, particularly Alzheimer’s disease and various vascular dementias. Over the past 20 years, dementia cases have increased by 20% and are expected to triple in the next 30 years due to aging. The cerebral vasculature becomes increasingly stiff and blood-brain barrier molecules degenerate during aging, leading to accumulation of T cells in the aged brain. The role of T cells on neuroinflammation and dementia during aging is a key unanswered question.Research questions/Hypothesis:How does vascular impairment impact immune cells and inflammation in the brain?How does aging impact immune cells and inflammation in the brain?Goals/Aims:To quantify and characterize T cells within the brain during aging and in a model of vascular contributions to cognitive impairment and dementia (VCID).To determine interactions between brain-resident immune cells (glia) and T cells in aging and a model of VCID.Methods/Approach:We isolated T cells and microglia from 3-month old and 21-month old brains in a model of vascular contributions to cognitive impairment and dementia (VCID). We performed single-cell RNA sequencing to identify and characterize peripheral and resident immune cells in the brain in the setting of typical aging and a model of VCID.Results:We identified a substantial increase inGzmk+ expressing effector memory CD8+ T cells in the brains of 21-month-old mice compared to 3-month-old mice. These cells were distinguished by their unique transcriptome, cytokine secretion profiles, and accumulation patterns. We also found a significant shift of microglia from an anti-inflammatory expression pattern toward a pro-inflammatory profile in the VCID group compared to control.Conclusions:We found a significant accumulation of age-associated T cells which may promote dementias. This study highlights the importance of using aged animal models to understand the cellular dynamics of chronic inflammatory diseases and dementias, potentially guiding the development of targeted therapeutic strategies.

Circulation, Volume 150, Issue Suppl_1, Page A4144467-A4144467, November 12, 2024. Previous studies have linked plasma levels of high-density lipoprotein cholesterol (HDL-C) with impaired cognitive function. However, few studies have investigated the associations between plasma HDL functionality and brain structure and function. Thus, our study aimed to elucidate the associations between plasma HDL measures and brain structure/function in a multiethnic cohort of middle-aged adults.Accordingly, we conducted a cross-sectional study in 1,826 adults (mean age 51.0±9.7 years, 58% female, 47% Black adults) without preexisting cardiovascular disease or stroke who participated in the Dallas Heart Study to determine associations between HDL measures and brain structure/function. Whole brain white matter hyperintensities (WMH) and grey matter volume (GMV) was measured using a 3-T MRI scanner and normalized to total cranial volume (TCV), and the Montreal Cognitive Assessment (MoCA) was used to measure cognition. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages and was expressed in arbitrary units. HDL particle measures were assessed using NMR spectroscopy. Adjusted multivariable linear regression models were performed with standardized beta estimates reported.Higher HDL-CEC and small HDL particles (HDL-P) were positively associated with GMV/TCV after adjustment for relevant risk factors (β=0.078 [95% CI: 0.029, 0.126],Figure, and β=0.063 [95% CI: 0.014, 0.111], respectively, all p0.05). Associations of HDL-CEC and small HDL-P with GMV were not modified by race/ethnicity or ApoE-ε4 status.In conclusion, higher HDL function and small HDL-P were associated with higher GMV after adjustment for traditional risk factors and were not modified by race/ethnicity or ApoE-ε4 carrier status. As such, these findings suggest that better HDL functionality is linked with larger brain GM volume in middle-aged adults. Since GMV loss has been linked to the development of mild cognitive impairment (MCI) and conversion of MCI to Alzheimer’s disease, our study may have implications for prevention of age-related decline in cognitive function.

Circulation, Volume 150, Issue Suppl_1, Page A4122290-A4122290, November 12, 2024. Background:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies.Objective:We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease.Methods:We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model.Results:A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69),P=0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49),P=0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98),P=0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25),P=0.61, I2=0%) was comparable between SGLT2i and control groups.Conclusion:Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.