The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12–1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Insulin resistance (IR)-related miRNAs have been associated with the development and progression of Alzheimer’s disease (AD). The dietary modulation of these miRNAs could become a potential strategy to manage AD. The aim of this study was to evaluate the effect of a high-fat diet (HFD), which aggravates AD-related pathogenic processes, on serum, cortex and hippocampus IR-related miRNA expression. C57BL/6J WT and APP_Swe/PS1dE9 mice were fed either an HFD or a conventional diet till 6 months of age. The mice fed with the HFD showed a significant increase in body weight and worsening glucose and insulin metabolism. miR-19a-3p was found to be up-regulated in the cortex, hippocampus and serum of APP/PS1 mice and in the serum and hippocampus of WT mice fed with the HFD. miR-34a-5p and miR-146a-5p were up-regulated in the serum of both groups of mice after consuming the HFD. Serum miR-29c-3p was overexpressed after consuming the HFD, along with hippocampal miR-338-3p and miR-125b-5p, only in WT mice. The HFD modulated the expression of peripheral and brain miRNAs related to glucose and insulin metabolism, suggesting the potential role of these miRNAs not only as therapeutic targets of AD but also as peripheral biomarkers for monitoring AD.

Background: Dementia risk is influenced by metabolic and lifestyle factors, including hyperinsulinemia, chronic inflammation, and type 2 diabetes. Glycemic index (GI) and glycemic load (GL) reflect the quality and quantity of dietary carbohydrates and their impact on glucose metabolism and systemic health. However, their associations with the risk of dementia subtypes remain unclear. This study examined the associations between dietary GI and GL and the risk of all-cause and different dementia subtypes, such as Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia. Methods: A prospective analysis was conducted by using data from 202 302 dementia-free participants in the UK Biobank cohort. Dietary GI and GL were estimated by using the Oxford WebQ 24-hour web-based dietary questionnaire. Cox proportional hazards regressions with restricted cubic splines were used to evaluate nonlinear relationships. Two-piece Cox models were used to identify inflection points, which served as reference values to estimate hazard ratios (HRs). Results: Dementia incidence was 0.89 per 1000 person-years. GI (mean±SD: 48.71 ± 7.68) showed an inverse J-shaped association with dementia risk, while GL (121.49 ± 39.00) showed a J-shaped pattern, with inflection points at 49.30 and 111.01, respectively. After adjusting for potential confounders, GI values of 111.01 were associated with higher dementia risk (HR, 1.145; 95% CI, 1.048–1.251). Similar findings were observed for AD and VD. Conclusion: Low-GI diets may offer protective effects against all-cause dementia, AD, and VD, whereas high-GL diets may increase the risk. These findings underscore the importance of considering both carbohydrate quality and quantity in dementia prevention and management strategies.

Given the importance of carbohydrates during pregnancy and the limited evidence on the impact of its excessive intake on offspring neurodevelopment, this study aimed to assess the associations between maternal glycemic index (GI) and glycemic load (GL) during early and late pregnancy and behavior problems in 4-year-old children, considering potential sex-related differences in susceptibility to maternal diet. This observational study included 188 mother–child pairs from the ECLIPSES study. GI and GL were estimated from a validated food frequency questionnaire. Offspring behavior was assessed using the Child Behavior Checklist 1.5–5. Multivariable linear and logistic regression analyses were employed to assess the association between GI, GL, and child behavior. Children of mothers in the highest tertile of GL during the first trimester of pregnancy showed elevated scores of both internalizing (β = 5.77; 95% CI, 2.28–9.26) and externalizing (β = 3.95; 95% CI, 0.70–7.19) problems, including anxiety and depression problems, withdrawn, attention problems, aggressive behavior, and attention-deficit/hyperactivity problems, as well as total (β = 5.24; 95% CI, 1.71–8.77) and autism spectrum problems (β = 3.30; 95% CI, 1.11–5.50). Similarly, higher odd ratios were observed for internalizing (OR = 2.37; 95% CI, 1.09–5.18), externalizing (OR = 3.46; 95% CI, 1.49–8.00), and total problems (OR = 3.83; 95% CI, 1.68–8.71). These associations were more pronounced in girls. No associations were observed during the third trimester. Regarding GI, no associations were found for the evaluated outcomes in any of the trimesters. Conclusion: These findings indicated that elevated maternal GL during the early pregnancy, but not later stages, was associated with adverse behavioral outcomes in offspring. Trial registration: EUCTR-2012–005480-28, NCT03196882. What is Known: • Carbohydrate intake is important during pregnancy as glucose is the main energy source for an optimal fetal brain development.• Elevated prenatal glycemic index and glycemic load have been associated with adverse offspring outcomes but their impact on behavioral development remains insufficiently explored. What is New:• A high maternal glycemic load during pregnancy may increase the risk of behavioral impairments in preschool-aged offspring.• Female offspring may be more vulnerable to behavioral disturbances to elevated maternal glycemic load during gestation.

Mateu-Fabregat J, et al. World J Mens Health. 2024 Apr;42:e53. https://doi.org/10.5534/wjmh.230328

Lipidomics offers potential for the early detection of Alzheimer’s disease (AD) and for elucidating the molecular mechanisms driving the progression from mild cognitive impairment (MCI) to AD. In this study, we investigated and validated the association between 139 cerebrospinal fluid (CSF) lipids and MCI-to-AD conversion. We included 400 MCI participants from the Ace Alzheimer Center Barcelona (ACE) cohort, all free of type 2 diabetes, comprising both ATN+ and ATN− individuals. After a median follow-up of 2.1 years, 142 participants progressed to AD dementia. We identified a multi-lipid signature of 11 lipids (including phosphatidylcholines, lysophosphatidylcholines, triglycerides, phosphatidylethanolamines, lysophosphatidylethanolamines and phosphatidylinositols) in CSF, which was associated with increased AD progression (HR = 1.85, 95% CI: 1.53–2.27). This signature was validated in paired plasma samples, a less invasive biofluid (HR = 1.26, 95% CI: 1.04–1.52) and in plasma samples from an external cohort of 189 participants (149 with subjective cognitive decline, 40 with MCI; β = 0.261, 95% CI: 0.022–0.500), demonstrating moderate-to-high predictive accuracy for MCI-to-AD progression. Counterfactual-based mediation analysis revealed that plasma phosphorylated tau-181 mediated up to 47% of the association between the lipid signature and AD dementia, highlighting glycerophospholipid metabolism as a key pathway. Exploratory Mendelian randomisation analyses suggested a potential causal association of lipid signature and AD, with two instrumental single-nucleotide polymorphisms mapped to loci implicated in neurodevelopmental and metabolic regulation (RBFOX1 and CDKAL1). In conclusion, our findings support the growing evidence of lipid metabolism dysregulation as an early marker of AD and identify plasma lipids reflecting CSF profiles that may be promising prognostic markers for AD dementia.