Excess sugar intake in early life may affect long-term brain health, but evidence for dementia is limited. We used the abrupt end of UK sugar rationing in September 1953 as a natural experiment to test whether exposure to sugar rationing during different windows within the first 1,000 days from conception was associated with adult risk of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD).

We analyzed UK Biobank participants born around the end of UK sugar rationing. Exposure was classified as rationing in utero only, in utero plus the first year of life, in utero plus 1-2 years of life, or no exposure. Incident dementia was identified from linked ICD-10 records. MRI of the brain and cognitive function were assessed in the imaging subcohort. Adjusted Cox and Gompertz models estimated HRs and 95% CIs, Fine-Gray models accounted for competing risk, and mediation analyses evaluated type 2 diabetes and hypertension.

Among 64,737 participants included in the analysis, the mean age at recruitment was 54.6 years, and 56.4% were women; 40,963 were exposed to sugar rationing during fetal and/or early-childhood life, and 23,774 were unexposed. Compared with unexposed individuals, sugar rationing in utero plus the first year of life was associated with lower hazards of all-cause dementia (HR, 0.79; 95% CI 0.66-0.94) and AD (HR, 0.77; 95% CI 0.59-1.00). Similar or slightly stronger associations were observed for exposure in utero plus 1-2 years (all-cause dementia: HR, 0.77; 95% CI 0.63-0.95; AD: HR, 0.72; 95% CI 0.53-0.98). Exposure in utero plus 1-2 years was associated with delayed onset of all-cause dementia by 2.55 years, AD by 2.87 years, and VaD by 2.49 years. Early-life sugar rationing was also associated with higher total gray matter volume (β, 3.27; 95% CI 0.46-6.07), lower white matter hyperintensity volume (β, -0.64; 95% CI -0.97 to -0.31), and better performance in processing speed and reasoning. Incident type 2 diabetes and hypertension jointly mediated 25.5% of the association.

Sugar restriction in the first 1,000 days was associated with lower dementia hazards, delayed onset, and more favorable brain-health profiles. These results support early-life sugar reduction as a potential strategy for dementia prevention.

Cardiovascular disease arises from interactions between inherited risk, molecular programmes, and tissue-scale remodelling that are observed clinically through imaging. Cardiac MRI (CMR), computed tomography (CT), and echocardiography are integral to routine cardiovascular care, while bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics are providing increasingly detailed molecular characterization of cardiac tissue. Yet, these imaging and molecular data are still analysed in largely separate pipelines. This review examines joint representations that link cardiac imaging phenotypes to transcriptomic and spatially resolved molecular states. An imaging-anchored perspective is adopted in which echocardiography, CMR, and CT define a spatial phenotype of the heart, and bulk, single-cell and spatial transcriptomics provide cell-type- and location-specific molecular context. We define the representation requirements of each modality, compare multimodal fusion strategies, and synthesize integrative pipelines for radiogenomics, spatial alignment, and image-based gene-expression prediction, together with their validation requirements, limitations, and failure modes. Spatial multiomic maps of human myocardium and atherosclerotic plaque, together with single-cell, spatial, and multimodal medical foundation models, are advancing imaging-anchored multiomics; however, cost, scalability, and tissue availability remain substantial barriers to large-scale cardiovascular translation.

Occupational hearing loss is a prevalent occupational disease with potential systemic health implications, including cardiovascular disease (CVD). This cross-sectional study investigated the association between hearing loss and 10-year CVD risk among middle-aged industrial workers in Tehran.

A total of 988 workers (83.7% male, mean age 46.8 ± 5.9 years) underwent routine occupational health examinations, including pure-tone audiometry and cardiovascular risk assessment using the WHO/ISH prediction chart. Hearing-loss phenotypes included low-frequency hearing loss (LFHL), high-frequency hearing loss (HFHL), overall hearing loss (HL), and noise-induced hearing loss (NIHL). Ear-specific hearing loss was first assessed separately for the left and right ears; participant-level hearing-loss variables were then defined based on the presence of hearing loss in either ear. The WHO/ISH 10-year CVD risk score was reported descriptively. To avoid conceptual overlap between the composite WHO/ISH score and its component variables, the composite CVD-risk variable was not entered into multivariable logistic regression models. Instead, multivariable logistic regression was used to identify demographic, occupational, and clinical factors associated with each hearing-loss phenotype.

The prevalence of NIHL was 19.9%. Ear-specific HFHL was observed in 27.2% of left ears and 25.5% of right ears, while LFHL was observed in 17.0% of left ears and 18.0% of right ears. In multivariable logistic regression models, sex and age were the most consistent independent factors associated with hearing loss. Female sex was associated with lower odds of LFHL, HFHL, overall HL, and NIHL compared with male sex. Older age was independently associated with LFHL, HFHL, and overall HL. Smoking was independently associated with HFHL and NIHL, while work experience was independently associated with NIHL. Job type and diabetes were not consistent independent predictors in the adjusted models. The composite WHO/ISH CVD-risk score was not included in the adjusted models to avoid conceptual overlap with its component variables.

These findings highlight the importance of demographic, behavioral, and occupational factors, particularly sex, age, smoking, and work experience, in occupational hearing loss among middle-aged industrial workers. Although predicted 10-year CVD risk was described in this occupational cohort, the composite WHO/ISH risk score was not included in multivariable models together with its component variables. Hearing conservation programs should integrate noise control, regular audiometric screening, smoking cessation, and cardiovascular risk assessment as complementary components of occupational health surveillance.

Heart failure (HF) remains a major public health challenge in Asia, with rising prevalence and disability burden. This study analyzed data from the 2021 Global Burden of Disease study (GBD 2021) to assess HF trends across 48 Asian countries from 1990 to 2021. In 2021, there were 29.5 million HF cases in Asia, a 155% increase since 1990, with an age-standardized prevalence rate rising from 583.62 to 633.76 per 100,000. Years lived with disability (YLDs) also surged by 155%, reaching 2.86 million in 2021. China accounted for 44.34% of Asia's HF cases, with the highest YLDs. Treated HF cases were most common, but severe HF contributed most to YLDs. The middle-high socio-demographic index (SDI) region had the highest age-standardized prevalence rate, while most SDI regions saw increasing trends, except Japan and Cyprus. The findings highlight the growing HF burden in Asia, urging targeted interventions to address this escalating health crisis.

Chronic limb threatening ischemia (CLTI) in older adults is associated with severe morbidity and high mortality. The rising prevalence is largely driven by the aging population and confronts healthcare systems with challenges like increasing demand for chronic care, staff shortage and rising healthcare costs. To improve post-operative outcomes and reduce the burden on healthcare systems, multimodal prehabilitation has gained interest and has the potential to improve post operative outcomes. However, evidence of the effect in older adults with CLTI remains scarce. The aim of this study is to determine whether a multimodal multicomponent prehabilitation program (MMPP) reduces length of stay and improves clinical, patient-reported and economic outcomes of older adults with CLTI. We developed a multicenter randomized controlled trial, with embedded cost-effectiveness analyses.. CLTI-patients aged 65 years or older, planned for revascularization, and their primary informal caregiver (IC) will be eligible. A total of 300 patients will be randomized to receive either standard preoperative care or a 2-week MMPP. All patients receive a general health screening. The MMPP includes physiotherapy and, if indicated, referral to a geriatrician, dietician or smoking-cessation coach, ferric carboxymaltose infusion or pre-arranged homecare. The primary outcome is length of stay. Exploratory secondary outcomes include minor complications, quality of life of patient and IC and health related quality of life. Descriptive secondary outcomes include 30-day and 6-month mortality, major complications, readmissions, burden on the IC, cost-effectiveness; and experiences and preferences regarding shared decision making. To the best of our knowledge, this is the first randomized controlled trial to evaluate the effect of an MMPP within older CLTI-patients. Findings will inform healthcare professionals whether an MMPP should be implemented in routine vascular surgical practice to reduce length of stay and improve clinical and patient-centered outcomes. The study is registered at the International Clinical Trials Registry Platform (NL-OMON58069).

Echocardiographic evaluation of left ventricular diastolic dysfunction (LVDD) remains ambiguous in asymptomatic elderly patients with preserved left ventricular ejection fraction (LVEF). This study aimed to assess the impact of the 2025 updated ASE guidelines on the diagnosis of LVDD in asymptomatic elderly inpatients with preserved ejection fraction, and to compare the diagnostic consistency of diastolic function grading between the 2016 and 2025 ASE guidelines.

A multi-center retrospective study was conducted. A total of 2058 elderly patients who underwent hospitalization and surgery between January 2025 and December 2025 were enrolled. Patients with LVEF <50% or cardiac symptoms were excluded. All subjects received a comprehensive transthoracic echocardiography. Left ventricular diastolic function was graded in accordance with the 2025 and 2016 ASE recommendations, respectively. The Kappa coefficient and overall agreement rate were calculated to analyze inter-guideline consistency.

Mean age was 70.8 ± 7.98 years, and 48.64% of patients were female. The prevalence of LVDD diagnosed according to the 2025 recommendations was higher than that diagnosed according to the 2016 guidelines (29.3% vs. 24%). Statistically significant inter-group differences were observed in core echocardiographic parameters across all diastolic function strata, including E/A ratio, e' peak velocity, average E/e' ratio, left atrial volume index (LAVi), and Tricuspid regurgitation peak velocity(TR) (p < 0.001). Using the 2016 criteria, 12.8% of patients were classified as indeterminate diastolic function. The 2025 ASE algorithm eliminated all indeterminate cases, reclassifying them as normal diastolic function (n = 80), grade 1 diastolic dysfunction (n = 108), and grade 2 diastolic dysfunction (n = 76). Moderate diagnostic consistency was identified between the two guidelines (Kappa = 0.441), with an overall agreement rate of 75.3%.

Compared with the 2016 ASE guidelines, the 2025 updated ASE recommendations optimize the evaluation framework for left ventricular diastolic function in elderly patients, markedly reduce diagnostic indeterminacy, improve detection rates of LVDD, and demonstrate superior clinical applicability and risk stratification value.

Growing evidence associates patent foramen ovale right-to-left shunt (PFO-RLS) with conditions including migraine, cryptogenic stroke (CS), and transient ischemic attack (TIA). However, the potential role of pulmonary right-to-left shunt (P-RLS) remains unclear. This study aimed to characterize PFO-RLS and P-RLS using contrast transesophageal echocardiography (cTEE) and analyze their distinct features and intrinsic associations with migraine and CS/TIA.

302 patients with clinically suspected right-to-left shunt (RLS) contrast transesophageal echocardiography (cTEE) between October 2019 and January 2025 were retrospectively analyzed. Target Symptom Group included patients presenting with migraine, cryptogenic stroke (CS), and/or transient ischemic attack (TIA); all other patients comprised the Comparison Group. cTEE was performed to detect and quantitatively evaluate both patent foramen ovale right-to-left shunt (PFO-RLS) and pulmonary right-to-left shunt (P-RLS). We conducted stratified analyses to assess the relationships of PFO-RLS and P-RLS individually with the presence of target symptoms. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with the Target Symptom Group.

All 302 patients were successfully examined using TTE and cTEE. cTEE revealed 165 cases of PFO-RLS and 217 cases of P-RLS. Stratified analyses showed no statistical significance of P-RLS among patients with varying degrees of PFO-RLS between the positive symptom and other symptoms group. PFO-RLS was statistically significant between the two groups in patients with varying degrees of P-RLS. Pulmonary vein shunt and PFO shunt were significantly associated with positive symptoms (p < 0.05) in the univariate analysis; however, only PFO shunt was an independent risk factor in the multivariate analysis (OR 1.363, p < 0.05). Patients with moderate-to-severe dual shunts had the highest proportion(76.5%) of positive symptoms. Further analysis showed no significant interaction (p > 0.05).

cTEE has a good diagnostic value for determining the source of RLS microvesicles. PFO-RLS causes migraine and CS/TIA; the more shunts there are, the more severe the symptoms. Current grading system for right-to-left shunt does not take microbubble size into consideration, although P-RLS is more common, it does not cause severe symptoms. A PFO shunt alone is an independent risk factor for migraine and CS/TIA.

This study aimed to evaluate the all-cause mortality predictive value of left atrioventricular coupling indexes in patients with chronic Chagas disease (CD).

This single-center retrospective longitudinal study included 382 patients with chronic CD. The left atrioventricular coupling index (LACI) was defined as the ratio of left atrial (LA) over left ventricular (LV) end-diastolic volumes. LA volumetric/mechanical coupling index (LAVI/A') was the ratio of maximum LA volume index over late diastolic mitral annulus velocity. The endpoint was a composite of all-cause mortality or heart transplant. The associations between LACI or LAVI/A' and the endpoint independent from clinical, electrocardiographic, and 2D echocardiographic parameters (Model I) or from Model I adjusting variables plus LV and LA strain parameters (Model II) were tested by multivariate Cox-proportional-hazards regression.

After a mean follow-up of 6.6 ± 2.7 years, 80 patients died and two underwent a heart transplant. LACI was associated with the endpoint in Models I (HR 1.03, 95% CI 1.01-1.05, p = 0.01) and II (HR 1.03, 95% CI 1.01-1.05, p = 0.0008). LAVI/A' was also associated with the endpoint in Models I (HR 1.08, 95% CI 1.05-1.12, P < 0.0001) and II (HR 1.09, 95% CI 1.05-1.12, P < 0.0001). The area under the ROC curve was larger for LAVI/A' than LACI (0.87 vs. 0.65, P < 0.0001). The optimal cutoff value for LAVI/A' was 3.3 mL × s/cm^-1 per m² (sensitivity 81.7%, specificity 83.7%). Patients with LAVI/A' ≥ 3.3 at baseline had a 19-fold higher risk for all-cause mortality.

New echocardiographic LA coupling indexes are promising predictors of dismal clinical outcomes in CD.

Current ASE/EACVI echocardiography guidelines recommend estimating central venous pressure from inferior vena cava (IVC) diameter and collapsibility in biventricular circulations. Because altered blood volume, venous capacitance, and venous tone may weaken the relationship between IVC morphology and systemic venous pressure, it is uncertain whether these criteria apply in the Fontan circulation.

In 101 adults with a Fontan circulation (median age 27.8 years), echocardiographic IVC and resting peripheral venous pressure (PVP) were measured simultaneously. ASE/EACVI guidelines were applied directly, estimating central venous pressure based on IVC diameter > 21 mm and collapsibility < 50%. Agreement with measured PVP categories was assessed using weighted κ. As a secondary post hoc analysis, IVC diameter and collapsibility thresholds were optimized within the same cohort to assess whether simple recalibration could materially improve agreement.

Median resting PVP was 10.6 (8.6-13.1) mmHg, and 21% had PVP ≥ 15 mmHg. IVC collapsibility was < 50% in 99%, whereas only 17% had IVC diameter > 21 mm. IVC diameter (r = 0.14, p = 0.163) and IVC collapsibility (r = -0.06, p = 0.527) did not correlate with PVP. Conventional criteria assigned no patient to the low pressure category and showed poor agreement with measured PVP (weighted κ 0.02, 95% confidence interval -0.12 to 0.16). Post hoc within-cohort recalibration (using IVC diameter ≥ 20 mm and collapsibility ≤ 10% as cut-offs) only modestly improved agreement (weighted κ 0.24, 95% confidence interval 0.05 to 0.42).

IVC-based pressure estimation is unreliable in adults with a Fontan circulation. Validated peripheral or invasive pressure measurements should be preferred for accurate Fontan pressure assessment.

Levodopa did not enhance early motor recovery at 3 months after stroke in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial. However, whether levodopa modifies the time course of recovery, leading to a delayed benefit remains unclear. Here, we examined levodopa's effects on the trajectories of motor recovery up to 6 months after stroke.

The ESTREL trial, a double-blind, randomised controlled clinical trial, compared a 39-day regimen of levodopa/carbidopa (100 mg/25 mg, 3×/day) to placebo alongside standardised task-oriented training. We longitudinally analysed Fugl-Meyer Motor Assessment (FMA) total scores (primary outcome), mRS and NIHSS (secondary outcomes) at baseline (0-7 days post stroke), 5 weeks, 3 and 6 months using linear mixed-effects models including timepoint, treatment allocation and their interaction.

In total, 576 of 610 (94%) participants (median age 73 years; 40% female) were analysed. FMA scores improved over time in both groups (P < .001), with no overall levodopa effect across visits (estimate 0.65 points, 95% CI, -3.3 to 4.6; P = .75). There was no indication that levodopa modified the recovery trajectory (χ2 = 0.52, df = 3, P = .91), and estimated levodopa-placebo differences in FMA changes across visit intervals were small, ranging from -0.7 to +0.8 points, with confidence intervals crossing zero. Secondary outcomes showed similar longitudinal improvement, without evidence of a treatment effect.

In this post hoc analysis of ESTREL participants with repeated FMA assessments, motor impairment improved from the first days after stroke up to 6 months. Levodopa added to task-oriented inpatient rehabilitation did not improve motor recovery or alter its trajectory over this period.

NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.